INDEX

Aarskog syndrome, 1–8 manifestations and management, albinism, 47 dental anomalies, 5–6 11–27 Costello syndrome, 225, 226 development and behavior problems, 5 musculoskeletal anomalies, 22–26 Down syndrome, 366 diagnostic criteria, 1–2 neurological anomalies, 17–20 Wolf–Hirschhorn syndrome, diagnostic testing, 4 respiratory anomalies, 20–21 270, 275 differential diagnosis, 4 Acrocallosal syndrome, differential diagnosis, Aicardi syndrome, differential diagnosis, deletion fetal anticonvulsant syndrome, 428 Greig cephalopolysyndactyly 1p36 syndrome, 255 Noonan syndrome, 654 syndrome, 710 Airway obstruction: etiology, pathogenesis, and genetics, 3–4 Acrofacial dysostoses, Nager syndrome, 809 Robin sequence, 807, 808 genital abnormalities, 6–7 Action myoclonus‐renal failure syndrome, 343 Stickler syndrome, 921 growth and feeding problems, 4–5 ACVRL1 gene mutation, hereditary hemorrhagic Treacher Collins syndrome, 931 incidence, 1 telangiectasia, 476 trisomy 13 and 18 syndromes, 952 manifestations and management, 4–7 ADAMTS2 gene, Ehlers–Danlos syndromes, 397 Alagille syndrome, 31–44 musculoskeletal anomalies, 6 Adaptive function: cardiovascular anomalies, 38–40 neurological anomalies, 6 Down syndrome, 363 development and behavior problems, 36 ophthalmologic anomalies, 5 fetal alcohol spectrum disorders, 413 diagnostic criteria, 32–34 Abnormal spontaneous brainstem activation, 801 fetal anticonvulsant syndrome, 431 diagnostic testing, 35 Acanthosis nigricans: 48,XXYY syndrome, 553 differential diagnosis, 35–36 achondroplasia, 11 Smith–Magenis syndrome, 873–874 deletion 22q11.2 syndrome, 298 Costello syndrome, 236 velo‐cardio‐facial syndrome, 300 etiology, pathogenesis, and genetics, 34–36 N‐acetylcysteine, Prader–Willi syndrome, 756 Adrenal insufficiency: genetic counseling, 35 Achondrogenesis type I, differential diagnosis, holoprosencephaly, 498 genitourinary anomalies, 40 osteogenesis imperfecta, 693 Pallister–Hall syndrome, 711 growth and feeding problems, 36 Achondroplasia, 9–30 Prader–Willi syndrome, 750, 751 incidence, 31–32 dental anomalies, 26 Adrenarche: manifestations and management, 36–41 development and behavior problems, 16–17COPYRIGHTEDATR‐X syndrome, 101 MATERIALmusculoskeletal anomalies, 40–41 diagnostic criteria, 9–10 Prader–Willi syndrome, 736 ophthalmologic anomalies, 40 diagnostic testing, 11 Silver–Russell syndrome, 844–845 Albinism, 45–59 differential diagnosis, 11 Smith–Magenis syndrome, 886 dermatologic anomalies, 50–52 ear anomalies, 21 Adrenocorticotropic hormone (ACTH): development and behavior problems, 50 etiology, pathogenesis, and genetics, 10–11 inverted duplicated chromosome 15 diagnostic criteria, 46–47 growth and feeding problems, 12–16 syndrome, 523 diagnostic testing, 47–49 hearing disorders, 21 Pallister–Hall syndrome, 711 differential diagnosis, 50 incidence, 9 Aging, premature: etiology, pathogenesis, and genetics, 47

Cassidy and Allanson’s Management of Genetic Syndromes, Fourth Edition. Edited by John C. Carey, Agatino Battaglia, David Viskochil, and Suzanne B. Cassidy. © 2021 John Wiley & Sons, Inc. Published 2021 by John Wiley & Sons, Inc.

1039

0004944829.INDD 1039 9/25/2020 7:13:41 AM 1040 INDEX

Albinism (cont’d) Angelman syndrome, 61–73 Aortic dilatation: gastrointestinal anomalies, 55 development and behavior problems, 66–69 in deletion 22q11.2 syndrome, 304 hearing disorders, 48 diagnostic criteria, 61 in hereditary hemorrhagic telangiectasia, 475 hematologic disorders, 53–54 diagnostic testing, 64–65 in Marfan syndrome, 577, 579, 581, 589, 593 incidence, 45–46 differential diagnosis, 65–66 in Pallister–Killian syndrome, 727 manifestations and management, 50–55 ATR‐X syndrome, 98, 99 in Sotos syndrome, 909 ophthalmologic anomalies, 52–53 deletion 1p36 syndrome, 255 in Turner syndrome, 981, 983 pulmonic anomalies, 54 deletion 5p syndrome, 283 Apert syndrome: Albright hereditary osteodystrophy, differential deletion 22q13 syndrome, 321 cardiovascular anomalies, 249 diagnosis, Prader–Willi syndrome, 741 inverted duplicated chromosome 15 development and behavior Alcohol consumption, fetal alcohol spectrum syndrome, 518 problems, 247 disorders, 405–424 Mowat–Wilson syndrome, 601 diagnostic criteria, 241–242 Allelic conditions: Rett syndrome, 797 diagnostic testing, 246 ATR‐X syndrome, 94–95 etiology, pathogenesis, and genetics, 61–62 etiology, pathogenesis, and genetics, 245 Juberg–Marsidi syndrome, 102 genetic counseling, 65 genitourinary anomalies, 250 Allelic pleiotropic developmental anomaly growth and feeding problems, 66 otolaryngologic anomalies, 248 syndromes: incidence, 61 skeletal anomalies, 249 Greig cephalopolysyndactyly syndrome, language difficulties, 67 Apneic deaths: 707–716 manifestations and management, 66–70 achondroplasia, 18, 19 Pallister–Hall syndrome, 707–716 musculoskeletal anomalies, 70 Turner syndrome, 982 Alobar holoprosencephaly, 487 neurological anomalies, 69–70 Apolipoprotein E (APOE gene), Down syndrome craniofacial anomalies, 497 ophthalmologic anomalies, 70 and Alzheimer disease, 359 development and behavior problems, Angiofibromas, tuberous sclerosis complex, 968 Arachnodactyly, Marfan syndrome, 588 495–496 Angiomyolipomas, tuberous sclerosis complex, Arachnoid cysts, Phelan–McDermid diagnostic criteria, 488 959, 970, 972 syndrome, 326 diagnostic testing, 494 Angiotensin‐converting enzyme (ACE) inhibitors, ARID1A gene mutations, Coffin–Siris etiology, pathogenesis, and genetics, 492 Marfan syndrome, 589, 593 syndrome, 189 incidence, 487–488 Angiotensin receptor blockers, Loeys–Dietz ARID1B gene mutations, Coffin–Siris syndrome, neurological anomalies, 498–499 syndrome, 566, 571 185, 189 Alopecia: Aniridia: Array comparative genomic hybridization Costello syndrome, 226, 236 aniridia associated keratopathy, 345 (aCGH): Down syndrome, 378 WAGR syndrome, 336, 342 ATR‐X syndrome, 97 incontinentia pigmenti, 509, 510 ANKRD11 gene Cornelia de Lange syndrome, 211 Cohen syndrome, 199 myotonic dystrophy type 1, 622 Anorectal anomalies: Cornelia de Lange syndrome, 212 Pallister–Killian syndrome, 718 Kabuki syndrome, 535 Pallister–Killian syndrome, 722 Turner syndrome, 990 Pallister–Killian syndrome, 727 Arrhythmias: Alstrom syndrome differential diagnosis: VATER/VACTERL association, 1000, 1001 Costello syndrome, 232 Bardet–Biedl syndrome, 112 Anosmia: myotonic dystrophy type 1, 621 Cohen syndrome, 199 Bardet–Biedl syndrome, 118 Noonan syndrome, 658 Alzheimer disease Down syndrome, 359, 365 CHARGE syndrome, 160, 161, 166 Arterial tortuosity syndrome: Amsterdam dwarfism. See Cornelia de Lange holoprosencephaly, 493 differential diagnosis syndrome Antiepileptics/anticonvulsants: Loeys–Dietz syndrome, 568 Amyloid precursor protein (APP) gene: fetal anticonvulsant syndrome, 425, 432 Marfan syndrome, 585 Down syndrome and Alzheimer disease, 365 fragile X syndrome, 450 Arteriohepatic dysplasia. See Alagille syndrome: fragile‐X syndrome, 443 Robin sequence, 811 Arthritis. See also Osteoarthritis: Amyoplasia arthrogryposis, 75, 77, 79–85 Smith–Magenis syndrome, 877 arthrogryposis, 85 Androgen replacement therapy: tuberous sclerosis complex, 967 Stickler syndrome, 922 49,XXXXY syndrome, 559 Antihistamines, Alagille syndrome, 37 Arthrogryposis, 75–91 Klinefelter syndrome, 550 Anti‐hypertensives: development and behavior problems, 84–85 Anemia: Loeys‐Dietz syndrome, 571 diagnostic criteria, 75–76 ATR‐X syndrome, 93, 101 Marfan syndrome, 593 diagnostic testing, 77 Cohen syndrome, 202 Anti‐RANK ligand antibody, osteogenesis differential diagnosis, 79 Cornelia de Lange syndrome, 217, 219 imperfecta, 697 ear anomalies, 88 Denys–Drash syndrome, 343 Anxiety: etiology, pathogenesis, and genetics, 77 Down syndrome, 379 Costello syndrome, 232 growth and feeding problems, 79–84 hereditary hemorrhagic telangiectasia, 478 Down syndrome, 364 hearing disorders, 88 Noonan syndrome, 660 fetal alcohol spectrum disorders, 415 incidence, 75 Proteus syndrome, 769 fragile X syndrome, 445 manifestations and management, 79–88 VATER/VACTERL association, 997 Klinefelter syndrome, 556 musculoskeletal anomalies, 85–87 Anesthesia risks: Noonan syndrome, 657 neurological anomalies, 87 achondroplasia, 26 Prader–Willi syndrome, 745 ophthalmologic anomalies, 87 myotonic dystrophy type 1, 624 Williams syndrome, 1026 respiratory anomalies, 87–88 Prader–Willi syndrome, 756 Aortic coarctation: Aryl hydrocarbon receptor nuclear translocator Rubinstein–Taybi syndrome, 832 neurofibromatosis type 1, 645 (ARNT), von Hippel–Lindau Treacher Collins syndrome, 933 Turner syndrome, 981 syndrome, 1006

0004944829.INDD 1040 9/25/2020 7:13:41 AM INDEX 1041

Assisted reproductive technology: Costello syndrome, 232 Stickler syndrome, 918 Beckwith–Wiedemann syndrome, 131 deletion 5p syndrome, 284 Back pain: Turner syndrome, 984–985 Down syndrome, 364 Loeys–Dietz syndrome, 570 Asthenic body habitus, Marfan syndrome, 587 fetal valproate syndrome, 431 Marfan syndrome, 587, 588, 591 ASXL1 gene mutations, Bohring–Opitz fragile X syndrome, 447 osteogenesis imperfecta, 694 syndrome, 212 inverted duplicated chromosome 15 syndrome, Sotos syndrome, 910 Ataxia: 517, 520–521 Bannayan–Riley–Ruvalcaba syndrome: Angelman syndrome, 64, 66 Kabuki syndrome, 532 development and behavior problems, 782 Bardet–Biedl syndrome, 118 Klinefelter syndrome, 545 diagnostic criteria, 776–777 deletion 22q11.2 syndrome, 304 myotonic dystrophy type 1, 618 diagnostic testing, 779 fragile X syndrome, 443, 445, 450 neurofibromatosis type 1, 632, 637 differential diagnosis, hereditary hemorrhagic Gorlin syndrome, 464 Noonan syndrome, 656 telangiectasia, 478 inverted duplicated chromosome 15 oculo‐auriculo‐vertebral spectrum, 674 and PTEN harmartoma tumor syndrome, 775 syndrome, 517 Pallister–Killian syndrome, 726 Bardet–Biedl syndrome, 107–123 velo‐cardio‐facial syndrome, 304 Phelan–McDermid syndrome, 317, 318, cardiovascular anomalies, 117 Williams syndrome, 1028 321, 323 dental anomalies, 118 Atherosclerosis, Turner syndrome, 982 Prader–Willi syndrome, 744 development and behavior problems, 113–114 ATR‐X syndrome, 93–105 PTEN hamartoma tumor syndrome, 786 diagnostic criteria, 108 asplenia, 103 Smith–Lemli–Opitz syndrome, 856 diagnostic testing, 112 cancer risk, 103 Smith–Magenis syndrome, 871, 875 differential diagnosis, 112 cardiovascular anomalies, 102 Sotos syndrome, 901, 906 Cohen syndrome, 199 dermatologic anomalies, 102 tuberous sclerosis complex, 965 Klinefelter syndrome, 542 development and behavior problems, 98–99 WAGR syndrome, 341 ear anomalies, 117–118 diagnostic criteria, 93–94 Williams syndrome, 1026 endocrine anomalies, 117 diagnostic testing, 96–98 Autoimmune disease: etiology, pathogenesis, and genetics, 108–112 differential diagnosis, 98 deletion 22q11.2 syndrome, 305 gastrointestinal anomalies, 118 Coffin–Lowry syndrome, 175 Down syndrome, 373, 378, 379, 380 genetic counseling, 111–112 Mowat–Wilson syndrome, 601 Klinefelter syndrome, 551, 552 genitourinary anomalies, 115–117 ear anomalies, 102 Noonan syndrome, 664 growth and feeding problems, 112–113 etiology, pathogenesis, and genetics, 94–96 Autonomic dysfunction: hearing disorders, 117–118 gastrointestinal anomalies, 100 Mowat–Wilson syndrome, 604 incidence, 107–108 genitourinary anomalies, 101–102 Prader–Willi syndrome, 749 manifestations and management, 112–118 growth and feeding problems, 98 Rett syndrome, 801 musculoskeletal anomalies, 115 hearing disorders, 102 Sotos syndrome, 907 neurological anomalies, 118 hematologic anomalies, 101 Autosomal dominant disorders: ophthalmologic anomalies, 114 incidence, 93 achondroplasia, 10 Barrett esophagus, Cornelia de Lange manifestations and management, 98–103 Alagille syndrome, 31 syndrome, 217 musculoskeletal anomalies, 102 brachymorphism‐onychodysplasia‐ Basal cell carcinomas, Gorlin syndrome, neurological anomalies, 100–101 dysphalangism syndrome, 186 465–466 ophthalmologic anomalies, 103 campomelic dysplasia, 693 Basilar invagination, osteogenesis imperfecta, 698 Attention deficit/hyperactivity disorder (ADHD): cherubism, 663 Bazex syndrome, differential diagnosis, Gorlin Aarskog syndrome, 5 Ehlers–Danlos syndromes, 392, 393, 394, 397, syndrome, 463 albinism, 50 402, 585 BBS1 mutations, Bardet–Biedl syndrome, 108, 109 deletion 5p syndrome, 284 holoprosencephaly, 492 BBS8 mutations, Bardet–Biedl syndrome, 111 deletion 22q11.2 syndrome, 301 Loeys–Dietz syndrome, 563, 585 BBS10 mutations, Bardet–Biedl syndrome, 108 Down syndrome, 364 Marfan syndrome, 577 B‐cells, Down syndrome, 379 47,XXY syndrome, 540, 544–545 Mowat–Wilson syndrome, 598 Beals syndrome, differential diagnosis: 48,XXYY syndrome, 553 myotonic dystrophy type 1, 616 Loeys–Dietz syndrome, 568 49,XXXXY syndrome, 556 neurofibromatosis type 1, 629 Marfan syndrome, 584 fragile X syndrome, 445 Nicolaides–Baraitser syndrome, 186 Beckwith–Wiedemann syndrome, 125–145 Klinefelter syndrome, 544–545 Noonan syndrome, 651 assisted reproductive technology offspring, 131 myotonic dystrophy type 1, 618 Pallister–Hall syndrome, 854 cardiovascular anomalies, 135 neurofibromatosis type 1, 632 PTEN hamartoma tumor syndrome, 775 chromosome 11p15, 130–131 Prader–Willi syndrome, 744 Stickler syndrome, 915, 918 clinical and molecular findings, 131 Smith–Magenis syndrome, 875 von Hippel–Lindau syndrome, 1007 craniofacial anomalies, 136 tuberous sclerosis complex, 965 Autosomal recessive disorders: development and behavior problems, 134–135 Turner syndrome, 986 diagnostic criteria, 126–127 Williams syndrome, 1026, 1027 Bardet–Biedl syndrome, 108–112 diagnostic testing, 132–133 Auriculo‐condylar syndrome, differential brittle cornea syndrome, 399 differential diagnosis, 133 diagnosis, oculo‐auriculo‐vertebral Cohen syndrome, 195–206 Costello syndrome, 228 spectrum, 673 Ehlers–Danlos syndromes, 400 Down syndrome, 361 Autism spectrum disorder (ASD): Goldberg– Shprintzen syndrome, 601 Gorlin syndrome, 463 cardio‐facio‐cutaneous syndrome, 150 homocystinuria, 586 Pallister–Killian syndrome, 724 Cohen syndrome, 200 ocular albinism, 46 endocrine anomalies, 135–136 Cornelia de Lange syndrome, 215 Smith–Lemli–Opitz syndrome, 852 etiology, pathogenesis, and genetics, 127–128

0004944829.INDD 1041 9/25/2020 7:13:41 AM 1042 INDEX

Beckwith–Wiedemann syndrome (cont’d) Sotos syndrome, 905–907 neurofibromatosis type 1, 643 gastrointestinal anomalies, 136–137 Stickler syndrome, 920 Wilms tumor, 343 genitourinary anomalies, 137 Treacher Collins syndrome, 930–931 BMP4 gene mutation, Stickler syndrome, 918 growth and feeding problems, 134 trisomy 13 and 18 syndromes, 946–947 Body composition: incidence, 125–126 tuberous sclerosis complex, 964–965 Prader–Willi syndrome, 742, 747, 750, 756 manifestations and management, 133–140 Turner syndrome, 985–987 Turner syndrome, 981, 987 molecular alterations, 128–131 VATER/VACTERL association, 998–999 Body mass index (BMI): neoplasia incidence, 137–139 von Hippel–Lindau syndrome, 1009–1010 achondroplasia, 12 nonchromosome methylation defects, 131–132 Williams syndrome, 1025–1028 Bardet–Biedl syndrome, 112 pregnancy and perinatal period, 139–140 Wolf–Hirschhorn syndrome, 270–271 Prader–Willi syndrome, 747 recurrence risks, 132 WT1‐related disorders, 344–345 Smith–Magenis syndrome, 872 unknown molecular etiology, 131 Benzodiazepines: Turner syndrome, 987 Wilms tumor, 138, 343 Phelan–McDermid syndrome, 325 Bohring–Opitz syndrome, differential diagnosis, Behavioral problems: Smith–Magenis syndrome, 877 Cornelia de Lange syndrome, 212 Aarskog syndrome, 5 Bernard–Soulier syndrome, deletion 22q11.2 Bone anomalies: achondroplasia, 16–17 syndrome, 306: arthrogryposis, 80 Alagille syndrome, 36 Beta‐blockers: Sotos syndrome, 910 albinism, 50 cardio‐facio‐cutaneous syndrome, 151 Bone cysts, tuberous sclerosis complex, 972 Angelman syndrome, 67 fragile X syndrome, 451 Bone dysplasias. See Musculoskeletal anomalies ATR‐X syndrome, 98–99 Loeys–Dietz syndrome, 571, 572 Börjeson–Forssman–Lehmann syndrome, Bardet–Biedl syndrome, 113–114 Marfan syndrome, 589 differential diagnosis: Beckwith–Wiedemann syndrome, 134–135 Rett syndrome, 803 Coffin–Lowry syndrome, 175 cardio‐facio‐cutaneous syndrome, 150 Williams syndrome, 1032 Coffin–Siris syndrome, 186 CHARGE syndrome, 161–162 Bevacizumab, hereditary hemorrhagic Botulinum toxin type A (Botox) injection: Coffin–Lowry syndrome, 177–178 telangiectasia, 479 ATR‐X syndrome, 100 Coffin–Siris syndrome, 187 Biallelic expression, Angelman syndrome, 61 Rett syndrome, 802, 803 Cohen syndrome, 200–201 Bicoronal synostosis, craniosynostosis Brachmann–de Lange syndrome. See Cornelia de Cornelia de Lange syndrome, 213–215 syndromes, 241, 242, 243 Lange syndrome Costello syndrome, 232 Bile duct anomalies: Brachymorphism‐onychodysplasia‐ craniosynostosis syndromes, 247 Alagille syndrome, 31, 32, 37 dysphalangism syndrome, differential deletion 1p36 syndrome, 256–257 Bardet–Biedl syndrome, 118 diagnosis, Coffin–Siris syndrome, 186 deletion 5p syndrome, 283–284 Down syndrome, 375 BRAF mutations, cardio‐facio‐cutaneous deletion 22q11.2 syndrome, 300–303 von Hippel–Lindau syndrome, 1014 syndrome, 148, 149, 153 Down syndrome, 363–366 Bilevel positive airway pressure (BiPAP), Brain anomalies: 49,XXXXY syndrome, 556 achondroplasia, 21 alobar holoprosencephaly, 487 fetal alcohol spectrum disorders, 413–415 Biliary atresia: deletion 1p36 syndrome, 257 fetal anticonvulsant syndrome, 435 differential diagnosis, Alagille syndrome, fragile X syndrome, 449 fragile X syndrome, 447–449 32, 35 hereditary hemorrhagic telangiectasia, 481 Gorlin syndrome, 464 trisomy 18 syndrome, 951 holoprosencephaly, 487–503 Greig cephalopolysyndactyly syndrome, 713 Biliary diversion, Alagille syndrome, 37 Klinefelter syndrome, 545 hereditary hemorrhagic telangiectasia, 478 Birt–Hogg–Dubé syndrome, differential Rett syndrome, 799 incontinentia pigmenti, 509 diagnosis: Smith–Lemli–Opitz syndrome, 857 inverted duplicated chromosome 15 syndrome, Smith–Magenis syndrome, 869 Smith–Magenis syndrome, 882 519–522 von Hippel–Lindau syndrome, 1008 syntelencephaly, 487 Kabuki syndrome, 532–533 Bisphosphonates: trisomy 13 and 18 syndromes, 947 Klinefelter syndrome, 543–547 Ehlers–Danlos syndromes, 400 tuberous sclerosis complex, 958, 965–966 Loeys–Dietz syndrome, 569 Klinefelter syndrome, 550 Williams syndrome, 1028 Marfan syndrome, 587 osteogenesis imperfecta, 695, 697, 698 Wolf–Hirschhorn syndrome, 272 Mowat–Wilson syndrome, 602–603 Prader–Willi syndrome, 755 Brainstem anomalies, Rett syndrome, 800, 801 myotonic dystrophy type 1, 618 Bladder anomalies: Branchio‐oto‐renal (BOR) syndrome, differential neurofibromatosis type 1, 637–638 cardio‐facio‐cutaneous syndrome, 152 diagnosis: Noonan syndrome, 656–657 Costello syndrome, 231, 235 Kabuki syndrome, 531 oculo‐auriculo‐vertebral spectrum, 674–675 Wolf–Hirschhorn syndrome, 276 oculo‐auriculo‐vertebral spectrum, 673 osteogenesis imperfecta, 695 Bladder exstrophy‐epispadias complex (BEEC) BRD4 mutations, Cornelia de Lange Pallister–Hall syndrome, 710 spectrum, deletion 1p36 syndrome, 260 syndrome, 210 Pallister–Killian syndrome, 725–726 Blaschko’s lines, incontinentia pigmenti, Breast anomalies: Phelan–McDermid syndrome, 322–325 508, 509 incontinentia pigmenti, 512 Prader–Willi syndrome, 739, 744–745 Bleeding disorders: PTEN hamartoma tumor syndrome, 782–783 Proteus syndrome, 767 Hermansky–Pudlak syndrome, 48–49 Breast cancer, PTEN hamartoma tumor PTEN hamartoma tumor syndrome, 782 Noonan syndrome, 659 syndrome, 782–783, 785 Robin sequence, 815–816 Blepharitis: Breastfeeding, fetal anticonvulsant Rubinstein–Taybi syndrome, 826–832 Cornelia de Lange syndrome, 218 syndrome, 434 Silver–Russell syndrome, 845 Down syndrome, 373 Brittle cornea syndrome. See Ehlers–Danlos Smith–Lemli–Opitz syndrome, 856–857 Blindness. See Vision impairment: syndromes Smith–Magenis syndrome, 872–878 Bloom syndrome, differential diagnosis: Bronchomalacia, Coffin–Siris syndrome, 190

0004944829.INDD 1042 9/25/2020 7:13:41 AM INDEX 1043

Bruising, Noonan syndrome, 659 ATR‐X syndrome, 102 CDKL5 mutations, inverted duplicated Brushfield spots, Down syndrome, 357 Bardet–Biedl syndrome, 117 chromosome 15 syndrome, 518 Bruxism: Beckwith–Wiedemann syndrome, 135 CDKL5 syndrome, differential diagnosis, Rett Cornelia de Lange syndrome, 216 cardio‐facio‐cutaneous syndrome, 151 syndrome, 795, 797 Down syndrome, 377 CHARGE syndrome, 163–164 CDKN1C mutations, Beckwith–Wiedemann Rett syndrome, 802, 803 Coffin–Lowry syndrome, 180 syndrome, 129 “Bull’s eye maculopathy,” Cohen syndrome, 201 Coffin–Siris syndrome, 189 CdLS spectrum disorder. See Cornelia de Lange Butterfly vertebrae: Cohen syndrome, 203 syndrome Alagille syndrome, 33, 40, 41 Cornelia de Lange syndrome, 218 Celiac disease: deletion 22q11.2 syndrome, 292, 298, 307 Costello syndrome, 226, 232 Down syndrome, 375, 376 craniosynostosis syndromes, 249 Turner syndrome, 988 Cachexia, Alagille syndrome, 36 deletion 1p36 syndrome, 258 Cellulitis, Phelan–McDermid syndrome, 330 Café‐au‐lait spots: deletion 5p syndrome, 285 Central apnea, trisomy 13 and 18 syndromes, 947 cardio‐facio‐cutaneous syndrome, 152 deletion 22q11.2 syndrome, 303–304 Central nervous system anomalies: deletion 22q11.2 syndrome, 330 Down syndrome, 357, 368–370 fetal alcohol spectrum disorders, 411 Gorlin syndrome, 465 Ehlers–Danlos syndromes, 391 holoprosencephaly, 489 neurofibromatosis type 1, 630, 634, 635, 637 fetal alcohol spectrum disorders, 416–417 myotonic dystrophy type 1, 615 Noonan syndrome, 663 fetal anticonvulsant syndrome, 436 neurofibromatosis type 1, 639–640 Calcium: fragile X syndrome, 451 Smith–Lemli–Opitz syndrome, 857 osteogenesis imperfecta, 701 Gorlin syndrome, 469–470 Smith–Magenis syndrome, 882 Prader–Willi syndrome, 755 Kabuki syndrome, 533–534 Central sleep apnea syndrome: Williams syndrome, 1029 Loeys–Dietz syndrome, 570–572 myotonic dystrophy type 1, 620 Callosal anomalies: Marfan syndrome, 588–590 Prader‐Willi syndrome, 753 Coffin–Lowry syndrome, 178 Mowat–Wilson syndrome, 604 Cerebellar tumors, von Hippel–Lindau syndrome, holoprosencephaly, 487 myotonic dystrophy type 1, 621–622 1010 Campomelic dysplasia, differential diagnosis, neurofibromatosis type 1, 645 Cerebral autosomal‐dominant arteriopathy with osteogenesis imperfecta, 693 Noonan syndrome, 657–658 subcortical infarcts and Camptodactyly, arthrogryposis, 75 oculo‐auriculo‐vertebral spectrum, 678 leukoencephalopathy (CADASIL) Carbamazepine, Smith–Magenis syndrome, 877 osteogenesis imperfecta, 700 syndrome, Alagille syndrome, 39 Carbamazepine embryopathy, fetal anticonvulsant Pallister–Killian syndrome, 727–728 Cerebral palsy, differential diagnosis: syndrome, 431–432 Phelan–McDermid syndrome, 328 Angelman syndrome, 65, 66 Cardiac disease, Alagille syndrome, 32, 38 Proteus syndrome, 771 Phelan–McDermid syndrome, 321 Cardiac fibromas, Gorlin syndrome, 469 Rett syndrome, 803 Cerebriform connective tissue nevus, Proteus Cardiac hypertrophy, Costello syndrome, 232 Rubinstein–Taybi syndrome, 830 syndrome, 763–764 Cardiac rhabdomyomas, tuberous sclerosis Smith–Lemli–Opitz syndrome, 858 Cerebro‐oculo‐facial‐skeletal syndrome, Robin complex, 959, 964, 969 Smith–Magenis syndrome, 885 sequence, 809 Cardio‐facio‐cutaneous syndrome, 147–155 Sotos syndrome, 908–909 Cerebro‐oculo‐facial syndrome, cardiovascular anomalies, 151 Stickler syndrome, 923 arthrogryposis, 75 dermatologic anomalies, 151–152 trisomy 13 and 18 syndromes, 948–949 Ceroid storage disease. See albinism development and behavior problems, 150 tuberous sclerosis complex, 969–970 Cervical spine: diagnostic criteria, 147–148 Turner syndrome, 981–983 Aarskog syndrome, 6 diagnostic testing, 149 VATER/VACTERL association, 999 achondroplasia, 20 differential diagnosis, 149 WAGR syndrome, 346 Down syndrome, 374 Costello syndrome, 230 Williams syndrome, 1030–1031 Cervicomedullary junction constriction, neurofibromatosis type 1, 635 Wolf–Hirschhorn syndrome, 272–273 achondroplasia, 18–20 Noonan syndrome, 653, 654–655 WT1‐related disorders, 346 CFC syndrome. See Cardio‐facio‐cutaneous etiology, pathogenesis, and genetics, 148 Carney syndrome, differential diagnosis, syndrome gastrointestinal anomalies, 150–151 neurofibromatosis type 1, 634 Charcot–Marie–Tooth disease, differential genitourinary anomalies, 152 Carrier testing, Cohen syndrome, 199 diagnosis, Denys–Drash syndrome, 343 growth and feeding problems, 150 Carter neurocognitive assessment, CHARGE syndrome, 157–170 hematologic anomalies, 153 holoprosencephaly, 496 cardiovascular anomalies, 163–164 incidence, 147 Cataracts: development and behavior problems, 161–162 Kabuki syndrome, 533–534 arthrogryposis, 87 diagnostic criteria, 158–159 manifestations and management, 149–153 cardio‐facio‐cutaneous syndrome, 152 diagnostic testing, 160 musculoskeletal anomalies, 152–153 Down syndrome, 373 differential diagnosis, 160–161 neoplasia incidence, 153 myotonic dystrophy type 1, 622 deletion 22q11.2 syndrome, 298 neurological anomalies, 151 Rubinstein–Taybi syndrome, 829 Kabuki syndrome, 531 ophthalmologic anomalies, 152 Smith–Lemli–Opitz syndrome, 858 trisomy 18 syndrome, 941 pregnancy, 149 Stickler syndrome, 921 ear anomalies, 165–166 retinitis pigmentosa, 659 trisomy 18 syndrome, 949 etiology, pathogenesis, and genetics, 159–160 Cardiomyopathy: Williams syndrome, 1032 genitourinary anomalies, 166 Hermansky–Pudlak syndrome, 55 Cat‐like cry, deletion 5p syndrome, 281 growth and feeding problems, 161 Sotos syndrome, 909 Cayler cardio‐facial syndrome, 22q11 deletion hearing disorders, 165–166 Cardiovascular anomalies: syndrome, 291 immunologic conditions, 166–167 Alagille syndrome, 32, 38–40 CBP mutations, Rubinstein–Taybi syndrome, 825 incidence, 157–158

0004944829.INDD 1043 9/25/2020 7:13:41 AM 1044 INDEX

CHARGE syndrome (cont’d) Cirrhosis: craniofacial anomalies, 189 manifestations and management, 161–167 Alagille syndrome, 37 development and behavior problems, 187 mortality, 157–158 Turner syndrome, 988 diagnostic criteria, 185 ophthalmologic anomalies, 162–163 Cleft lip and palate: differential diagnosis, 186–187 respiratory anomalies, 164–165 Apert syndrome, 246 Cornelia de Lange syndrome, 212 CHD4 mutations, Pallister–Killian CHARGE syndrome, 164 etiology, pathogenesis, and genetics, 186 syndrome, 721 Cornelia de Lange syndrome, 216 gastrointestinal anomalies, 191 CHD7 mutations: deletion 22q11.2 syndrome, 292, 302–303 genitourinary anomalies, 191 CHARGE syndrome, 158, 159–160, 161 fetal anticonvulsant syndrome, 432–433, 436 growth and feeding problems, 187 Kallmann syndrome, 160 holoprosencephaly, 495 hearing disorders, 191 Chediak–Higashi syndrome, 46 incontinentia pigmenti, 512 immunologic conditions, 191 Chest deformities: Kabuki syndrome, 535 incidence, 185 ATR‐X syndrome, 102 oculo‐auriculo‐vertebral spectrum, 675 manifestations and management, 187–192 Marfan syndrome, 587 Pallister–Hall syndrome, 712 musculoskeletal anomalies, 189 Childhood apraxia of speech, 49,XXXXY Robin sequence, 808, 814, 818–819 neoplasia incidence, 191–192 syndrome, 556 Smith–Lemli–Opitz syndrome, 857, 858 neurological anomalies, 189 Child maltreatment, differential diagnosis, Stickler syndrome, 920, 921, 922 ophthalmologic anomalies, 191 osteogenesis imperfecta, 693 Treacher Collins syndrome, 931, 932 respiratory anomalies, 190 Choanal atresia: trisomy 13 syndrome, 941–942 Cognitive function. See also Mental retardation CHARGE syndrome, 157, 158, 164 Clinodactyly, Silver–Russell syndrome, 846 Aarskog syndrome, 5 Treacher Collins syndrome, 932 Clonidine, Phelan–McDermid syndrome, 325 achondroplasia, 16 Cholelithiasis, myotonic dystrophy Cloverleaf skull, craniosynostosis syndromes, Angelman syndrome, 66–67 type 1, 620 243, 246, 249 Bardet–Biedl syndrome, 113 Cholestasis, Alagille syndrome, 35, 36, 37 CLOVE syndrome, differential diagnosis, Proteus Coffin–Lowry syndrome, 178 Cholesterol: syndrome, 766 deletion 5p syndrome, 282 Down syndrome, 366 Clubfeet. See also Foot anomalies Down syndrome, 364 holoprosencephaly, 490 arthrogryposis, 75 holoprosencephaly, 499 Cholesterol‐directed therapies, Smith–Lemli– Ehlers–Danlos syndromes, 394, 401 Klinefelter syndrome, 553 Opitz syndrome, 854–855 fragile X syndrome, 452 Prader–Willi syndrome, 744 Chondrodysplasias. See Musculoskeletal myotonic dystrophy type 1, 623 Smith–Lemli–Opitz syndrome, 856 anomalies oculo‐auriculo‐vertebral spectrum, 678 Smith–Magenis syndrome, 873 Chondrogenesis type I, differential diagnosis, velo‐cardio‐facial syndrome, 292 Sotos syndrome, 905 osteogenesis imperfecta, 693 Coagulation disorders: Williams syndrome, 1025–1026 CHOPS syndrome, differential diagnosis, differential diagnosis, Ehlers–Danlos WT1‐related disorders, 341 Cornelia de Lange syndrome, 212 syndromes, 394 Cohen syndrome, 195–206 Chorioangiomas, Noonan syndrome, 661 Hermansky–Pudlak syndrome, 54 cardiovascular anomalies, 203 Choroid plexus cysts, trisomy 18 syndrome, 940 Noonan syndrome, 659–660 dental anomalies, 204 Chromosome analysis: vascular EDS, 394 development and behavior problems, 200–201 Angelman syndrome, 64 Coenzyme Q10, Prader–Willi syndrome, diagnostic criteria, 195–198 craniosynostosis syndromes, 246 749, 750 diagnostic testing, 199 deletion 1p36 syndrome, 254 Coffin–Lowry syndrome, 171–184 differential diagnosis, 199–200 deletion 5p syndrome, 283 cardiovascular anomalies, 180 deletion 1p36 syndrome, 255 deletion 22q13 syndrome, 317, 321 dental anomalies, 181 endocrine anomalies, 202 Down syndrome, 360 development and behavior problems, 177–178 etiology, pathogenesis, and genetics, Gorlin syndrome, 462 diagnostic criteria, 171–172 198–199 incontinentia pigmenti, 510 diagnostic testing, 174–175 growth and feeding problems, 200 inverted duplicated chromosome 15 differential diagnosis, 175 hematologic anomalies, 202–203 syndrome, 518 ATR‐X syndrome, 98 immunologic conditions, 202 Klinefelter syndrome, 541 fetal anticonvulsant syndrome, 428 incidence, 195 Noonan syndrome, 661 Williams syndrome, 1024 manifestations and management, 200–204 oculo‐auriculo‐vertebral spectrum, 673 ear anomalies, 180 musculoskeletal anomalies, 203–204 Phelan–McDermid syndrome, 317 etiology, pathogenesis, and genetics, 172–174 neurological anomalies, 202 Prader–Willi syndrome, 736, 740, 741 gastrointestinal anomalies, 181 ophthalmologic anomalies, 201–202 Silver–Russell syndrome, 841 growth and feeding problems, 175 respiratory anomalies, 203 Smith–Lemli–Opitz syndrome, 854, 859 hand anomalies, 172 Cohesin complex, Cornelia de Lange Smith–Magenis syndrome, 864, 871 hearing disorders, 180 syndrome, 210 trisomy 13 syndrome, 943 incidence, 171 COL1A2 gene mutation, cardiac‐valvular trisomy 18 syndrome, 938, 940 manifestations and management, 175–182 EDS, 393 Turner syndrome, 977 musculoskeletal anomalies, 181 COL2A1 gene mutation, Stickler syndrome, WAGR syndrome, 336 neoplasia incidence, 181–182 917, 918 Williams syndrome, 1023 neurological anomalies, 178–179 COL9A2/COL9A3 gene mutation, Stickler Wolf–Hirschhorn syndrome, 267 ophthalmologic anomalies, 179 syndrome, 918 Chylothorax, Noonan syndrome, 661 respiratory anomalies, 180 COL11A1 gene mutation: “Cigarette paper” scars, Ehlers–Danlos Coffin–Siris syndrome, 185–194 Marshall syndrome, 919–920 syndromes, 391 cardiovascular anomalies, 189 Stickler syndrome, 918, 919–920

0004944829.INDD 1044 9/25/2020 7:13:42 AM INDEX 1045

COL12A1 gene mutation, myopathic EDS, 401 fragile X syndrome, 444 Costello syndrome, 225–240 Collagen anomalies: Kabuki syndrome, 531, 533 cardiovascular anomalies, 232–233 Ehlers–Danlos syndromes, 391, 392 Loeys–Dietz syndrome, 563, 567, 568, dermatologic anomalies, 236 Marfan syndrome, 585 571, 573 development and behavior problems, 232 osteogenesis imperfecta, 683 Marfan syndrome, 582, 586 diagnostic criteria, 225–226 Stickler syndrome, 915, 917–918 Stickler syndrome, 915 diagnostic testing, 226–228 Collagenopathy, type I, differential diagnosis, Williams syndrome, 1022 differential diagnosis, 228–230 Silver–Russell syndrome, 843 Conotruncal anomalies: Beckwith–Wiedemann syndrome, 133 Coloboma: CHARGE syndrome, 163 cardio‐facio‐cutaneous syndrome, 149 CHARGE syndrome, 157, 158, 159, 162, 163 deletion 22q11.2 syndrome, 291 neurofibromatosis type 1, 635 deletion 1p36 syndrome, 259 Smith–Lemli–Opitz syndrome, 858 endocrine anomalies, 235 Gorlin syndrome, 469 Constipation: etiology, pathogenesis, and genetics, 226 holoprosencephaly, 492, 500 ATR‐X syndrome, 100 growth and feeding problems, 231 Kabuki syndrome, 531 cardio‐facio‐cutaneous syndrome, 150–151 incidence, 225 Mowat–Wilson syndrome, 605 Coffin–Siris syndrome, 191 manifestations and management, 230–236 oculo‐auriculo‐vertebral spectrum, 671, deletion 1p36 syndrome, 260 musculoskeletal anomalies, 233–234 673, 677 deletion 5p syndrome, 286 neoplasia incidence, 235–236 Rubinstein–Taybi syndrome, 829 deletion 22q11.2 syndrome, 298 neurological anomalies, 234–235 Treacher Collins syndrome, 927, 930, 932 holoprosencephaly, 500 ophthalmologic anomalies, 235 trisomy 13 syndrome, 949 Loeys–Dietz syndrome, 573 respiratory anomalies, 233 velo‐cardio‐facial syndrome, 306 Phelan–McDermid syndrome, 329 Cowden syndrome. See also PTEN hamartoma Wolf–Hirschhorn syndrome, 274 Rett syndrome, 803 tumor syndrome Colonic hypoganglionosis, ATR‐X Rubinstein–Taybi syndrome, 828, 829, 831 dermatologic anomalies, 785 syndrome, 100 Silver–Russell syndrome, 844 development and behavior problems, 782 Common variable immunodeficiency: Smith–Magenis syndrome, 885 diagnostic criteria, 775–776 Smith–Magenis syndrome, 869 Sotos syndrome, 911 diagnostic testing, 779 Wolf–Hirschhorn syndrome, 275 trisomy 13 and 18 syndromes, 951 differential diagnosis Conductive hearing loss. See also Hearing Williams syndrome, 1031 Gorlin syndrome, 463 disorders Continuous positive airway pressure (CPAP): Proteus syndrome, 766 Cornelia de Lange syndrome, 216 achondroplasia, 20, 21 etiology, pathogenesis, and genetics, 778 deletion 5p syndrome, 285 Down syndrome, 377 incidence, 775 Down syndrome, 371 fragile X syndrome, 451 CPLX1 gene, Wolf–Hirschhorn syndrome, 268 fragile X syndrome, 451 Loeys–Dietz syndrome, 573 Cranial nerve anomalies: Kabuki syndrome, 534 myotonic dystrophy type 1, 621 CHARGE syndrome, 161 Marfan syndrome, 585 Prader–Willi syndrome, 753, 754 oculo‐auriculo‐vertebral spectrum, 677 Mowat–Wilson syndrome, 605 Rett syndrome, 801 Cranio‐cerebello‐cardiac (3C) syndrome, oculo‐auriculo‐vertebral spectrum, 676, 677 Treacher Collins syndrome, 932 differential diagnosis, Noonan osteogenesis imperfecta, 698 COP9 gene mutation, Smith–Magenis syndrome, 655 Pallister–Killian syndrome, 729 syndrome, 869 Craniofacial anomalies. See also Facial Proteus syndrome, 770 Cornelia de Lange syndrome, 207–223 anomalies; Microcephaly Robin sequence, 815 cardiovascular anomalies, 218 Beckwith–Wiedemann syndrome, 136 Smith–Magenis syndrome, 867, 881 craniofacial anomalies, 216 carbamazepine embryopathy, 431 Sotos syndrome, 908 dermatologic anomalies, 220 cardio‐facio‐cutaneous syndrome, 147 Stickler syndrome, 918, 922 development and behavior problems, Coffin–Lowry syndrome, 171, 172 Treacher Collins syndrome, 933 213–215 Coffin–Siris syndrome, 189 Turner syndrome, 989 diagnostic criteria, 207–210 Cornelia de Lange syndrome, 216 velo‐cardio‐facial syndrome, 307 diagnostic testing, 211–212 craniosynostosis syndromes, 247–248 Congenital contractural arachnodactyly. See differential diagnosis, 212–213 deletion 5p syndrome, 284–285 Beals syndrome Coffin–Siris syndrome, 187 deletion 22q11.2 syndrome, 302–303 Congenital contractures: Rubinstein–Taybi syndrome, 826 Down syndrome, 383 arthrogryposis, 75, 77, 79, 85, 87 ear anomalies, 215–216 Ehlers–Danlos syndromes, 394, 397, 400 Ehlers–Danlos syndromes, 400, 401 etiology, pathogenesis, and genetics, 210–211 fetal anticonvulsant syndrome, 436–437 myotonic dystrophy type 1, 622 gastrointestinal anomalies, 218 fragile X syndrome, 450–451 osteogenesis imperfecta, 690 genitourinary anomalies, 218–219 Gorlin syndrome, 464 Congenital diaphragmatic hernia, Pallister– growth and feeding problems, 213 holoprosencephaly, 489, 497 Killian syndrome, 718–719, 727 hearing disorders, 215–216 Kabuki syndrome, 535 Congenital heart defects. See Cardiovascular hematologic disorders, 219–220 Loeys–Dietz syndrome, 570 anomalies immunologic conditions, 219–220 myotonic dystrophy type 1, 619 Congenital heart disease. See Cardiovascular incidence, 207 oculo‐auriculo‐vertebral spectrum, 675–676 anomalies manifestations and management, 213–220 Phelan–McDermid syndrome, 318 Connective tissue disorders: musculoskeletal anomalies, 216–217 Rett syndrome, 800 arthrogryposis, 77 neurological anomalies, 219 Robin sequence, 817–819 Costello syndrome, 225 ophthalmologic anomalies, 218 Silver–Russell syndrome, 845 Ehlers–Danlos syndromes, 389, 392, 395, Corpus callosum abnormalities, Smith–Lemli– Smith–Lemli–Opitz syndrome, 852 396, 397 Opitz syndrome, 857 Smith–Magenis syndrome, 884

0004944829.INDD 1045 9/25/2020 7:13:42 AM 1046 INDEX

Craniofacial anomalies (cont’d) Smith–Lemli–Opitz syndrome, 859, 860 diagnostic testing, 282–283 Stickler syndrome, 921–922 velo‐cardio‐facial syndrome, 306 differential diagnosis, 283 Treacher Collins syndrome, 931–932 Wolf–Hirschhorn syndrome, 273 ear anomalies, 285–286 trisomy 13 syndrome, 941, 942 CTNND2 gene, deletion 5p syndrome, 282 etiology, pathogenesis, and Williams syndrome, 1023 Curaҫao criteria, hereditary hemorrhagic genetics, 282 Wolf–Hirschhorn syndrome, 266, 267 telangiectasia, 477 gastrointestinal anomalies, 286–287 Craniofrontonasal syndrome, differential Cutis laxa: genetic counseling, 282 diagnosis, craniosynostosis deletion 1p36 syndrome, 261 genitourinary anomalies, 285 syndromes, 246 differential diagnosis, Loeys–Dietz growth and feeding problems, 283 Craniosynostosis syndromes, 241–251. See also syndrome, 568 hearing disorders, 285–286 Apert syndrome; Crouzon syndrome; Cutis marmorata: incidence, 281 Muenke syndrome; Pfeiffer syndrome; Cornelia de Lange syndrome, 220 manifestations and management, 283–287 Saethre–Chotzen syndrome Down syndrome, 358, 378 musculoskeletal anomalies, 286 cardiovascular anomalies, 249 Cutis verticis gyrata, Cornelia de Lange neurological anomalies, 285 craniofacial anomalies, 247–248 syndrome, 220 ophthalmologic anomalies, 286 development and behavior problems, 247 Cyanosis, CHARGE syndrome, 163 respiratory anomalies, 287 diagnostic criteria, 241–246 Cyclopia, holoprosencephaly, 497 Deletion 22q11.2 syndrome, 291–316 diagnostic testing, 246 CYFIP mutation, fragile X syndrome, 445 cardiovascular anomalies, 303–304 differential diagnosis, 246 Cylindromatosis, differential diagnosis, Gorlin craniofacial anomalies, 302–303 deletion 22q11.2 syndrome, 298 syndrome, 463 development and behavior problems, 300–302 etiology, pathogenesis, and genetics, 245–246 Cystic hygromas: diagnostic criteria, 292 genitourinary anomalies, 250 Noonan syndrome, 661 diagnostic testing, 295–298 growth and feeding problems, 246–247 Turner syndrome, 983, 984 differential diagnosis, 298 incidence, 241 Cystic kidney disease: Alagille syndrome, 35 manifestations and management, 246–250 Bardet–Biedl syndrome, 115 deletion 5p syndrome, 283 musculoskeletal anomalies, 249 tuberous sclerosis complex, 970 Kabuki syndrome, 531 neurological anomalies, 249 Cystic neuroendocrine tumors, 1014 Smith–Magenis syndrome, 871 ophthalmologic anomalies, 248–249 Cytosolic serine hydroxymethyltransferase ear anomalies, 307 otolaryngologic anomalies, 248 (cSHMT), Smith–Magenis syndrome, 869 endocrine anomalies, 306 CREB3LI gene mutation, osteogenesis etiology, pathogenesis, and genetics, 292–295 imperfecta, 691 Deafness. See Hearing disorders: genetic counseling, 294–295 CREB‐binding protein, Rubinstein–Taybi Deafness, onychodystrophy, osteodystrophy, genitourinary anomalies, 306 syndrome, 825 mental retardation, and seizures (DOORS) growth and feeding problems, 298–300 CREST syndrome, differential diagnosis, syndrome, differential diagnosis, hearing disorders, 307 hereditary hemorrhagic Coffin–Siris syndrome, 187 immunologic conditions, 305–306 telangiectasia, 478 Deletion 1p36 syndrome, 253–264 incidence, 291–292 Crohn’s disease, Turner syndrome, 988 adulthood, 261 manifestations and management, 298–308 Crouzon syndrome. See also Craniosynostosis cardiovascular anomalies, 258 musculoskeletal anomalies, 307–308 syndromes dermatologic anomalies, 261 neuromuscular anomalies, 304–305 development and behavior problems, 247 development and behavior problems, 256–257 ophthalmologic anomalies, 306–307 diagnostic criteria, 242–243 diagnostic criteria, 253–254 psychiatric problems, 300–302 diagnostic testing, 246 diagnostic testing, 255 respiratory anomalies, 303 etiology, pathogenesis, and genetics, 245 differential diagnosis, 255–256 and Robin sequence, 809, 810, 813 growth and feeding problems, 246 Cohen syndrome, 199 Deletion 22q13 syndrome. See Phelan– Crowe’s sign, neurofibromatosis type 1, 630 ear anomalies, 259 McDermid syndrome Cryptorchidism: endocrine anomalies, 260–261 Denosumab, osteogenesis imperfecta, 697 Aarskog syndrome, 6 etiology, pathogenesis, and genetics, 254–255 Dental anomalies: ATR‐X syndrome, 94, 102 gastrointestinal anomalies, 260 Aarskog syndrome, 5–6 Bardet–Biedl syndrome, 116 genitourinary anomalies, 260 achondroplasia, 26 cardio‐facio‐cutaneous syndrome, 152 growth and feeding problems, 256 Bardet–Biedl syndrome, 118 CHARGE syndrome, 166 hearing disorders, 259 Coffin–Lowry syndrome, 181 Coffin–Siris syndrome, 191 incidence, 253 Cohen syndrome, 204 Cornelia de Lange syndrome, 218 manifestations and management, 256–261 Cornelia de Lange syndrome, 216 craniosynostosis syndromes, 250 musculoskeletal anomalies, 259–260 deletion 5p syndrome, 284 deletion 1p36 syndrome, 260 neoplasia incidence, 261 Down syndrome, 377–378 deletion 5p syndrome, 285 neurological anomalies, 257–258 fetal alcohol spectrum disorders, 416 Denys–Drash syndrome, 336, 340, 346, 347 ophthalmologic anomalies, 259 Gorlin syndrome, 467–468 Down syndrome, 370, 382, 383 respiratory anomalies, 258–259 incontinentia pigmenti, 512 fetal anticonvulsant syndrome, 437 Deletion 4p. See Wolf–Hirschhorn syndrome Kabuki syndrome, 535 Kabuki syndrome, 536 Deletion 5p syndrome, 281–289 myotonic dystrophy type 1, 619 Klinefelter syndrome, 540, 554, 557 aging and life expectancy, 287 osteogenesis imperfecta, 699 Noonan syndrome, 662 cardiovascular anomalies, 285 Pallister–Hall syndrome, 713 Pallister–Killian syndrome, 720, 728 craniofacial anomalies, 284–285 Pallister–Killian syndrome, 730 Prader–Willi syndrome, 751 development and behavior problems, 283–284 Phelan–McDermid syndrome, 328 Rubinstein–Taybi syndrome, 831 diagnostic criteria, 281 Prader–Willi syndrome, 754

0004944829.INDD 1046 9/25/2020 7:13:42 AM INDEX 1047

Proteus syndrome, 772 Angelman syndrome, 66–69 Diabetes mellitus: Rett syndrome, 802–803 arthrogryposis, 84–85 Bardet–Biedl syndrome, 117 Rubinstein–Taybi syndrome, 830 ATR‐X syndrome, 98–99 Cohen syndrome, 202 Silver–Russell syndrome, 845 Bardet–Biedl syndrome, 113–114 holoprosencephaly, 490 Smith–Magenis syndrome, 884 Beckwith–Wiedemann syndrome, 134–135 Klinefelter syndrome, 549, 552 Sotos syndrome, 908 cardio‐facio‐cutaneous syndrome, 150 Prader–Willi syndrome, 751, 752 Treacher Collins syndrome, 931, 932 CHARGE syndrome, 161–162 Turner syndrome, 987 tuberous sclerosis complex, 972 Coffin–Lowry syndrome, 177–178 Williams syndrome, 1029, 1030 Turner syndrome, 989 Coffin–Siris syndrome, 188 Diabetic embryopathy, Robin sequence, 810 Williams syndrome, 1033–1034 Cohen syndrome, 200–201 Diaphragmatic hernia, WT1‐related disorders, 341 Wolf–Hirschhorn syndrome, 274 Cornelia de Lange syndrome, 209, 213–215 Diarrhea, Phelan–McDermid syndrome, 329 Denys–Drash syndrome: Costello syndrome, 232 DICER1 syndrome, Wilms tumor, 343 development and behavior problems, 344–345 craniosynostosis syndromes, 247 Diet: diagnostic criteria, 336–337 deletion 1p36 syndrome, 256–257 Alagille syndrome, 36 diagnostic testing, 341–342 deletion 5p syndrome, 283–284 Angelman syndrome, 70 differential diagnosis, 342–343 deletion 22q11.2 syndrome, 300–303 DiGeorge syndrome. See Deletion 22q11.2 ear anomalies, 345 Down syndrome, 363–366 syndrome etiology, pathogenesis, and genetics, 339 49,XXXXY syndrome, 556 Disintegrative infantile psychosis, Rett genitourinary anomalies, 346–348 fetal alcohol spectrum disorders, 413–415 syndrome, 797 growth and feeding problems, 343–344 fetal anticonvulsant syndrome, 435 Dislocated hips: hearing disorders, 345 fragile X syndrome, 447–449 arthrogryposis, 75, 87 incidence, 335 Gorlin syndrome, 464 Smith–Lemli–Opitz syndrome, 860 manifestations and management, 343–349 Greig cephalopolysyndactyly syndrome, 713 Disomy: musculoskeletal anomalies, 345 hereditary hemorrhagic telangiectasia, 478 Angelman syndrome, 62, 64, 65 neoplasia incidence, 348–349 incontinentia pigmenti, 509 Beckwith–Wiedemann syndrome, 127, neurological anomalies, 344–345 inverted duplicated chromosome 15 syndrome, 130–131, 132 ophthalmologic anomalies, 345–346 519–522 Cohen syndrome, 199 pulmonary anomalies, 346 Kabuki syndrome, 532–533 Prader–Willi syndrome, 735, 739, 740 Dermatologic anomalies: Klinefelter syndrome, 543–547 Distal arthrogryposis type 1, differential albinism, 50–52 Loeys–Dietz syndrome, 569 diagnosis, trisomy 18 syndrome, 941 ATR‐X syndrome, 102 Marfan syndrome, 587 Distal digital hypoplasia, fetal anticonvulsant cardio‐facio‐cutaneous syndrome, 151–152 Mowat–Wilson syndrome, 602–603 syndrome, 437 Cohen syndrome, 203 myotonic dystrophy type 1, 618 Distraction osteogenesis, Treacher Collins Cornelia de Lange syndrome, 220 neurofibromatosis type 1, 637–638 syndrome, 932 Costello syndrome, 226, 236 Noonan syndrome, 656–657 Diverticulus, Williams syndrome, 1031 deletion 1p36 syndrome, 261 oculo‐auriculo‐vertebral spectrum, 674–675 DNAH5 (dynein axonemal heavy chain 5) gene, Down syndrome, 378 osteogenesis imperfecta, 695 deletion 5p syndrome, 287 Ehlers–Danlos syndromes, 397 Pallister–Hall syndrome, 710 DNA methylation: Gorlin syndrome, 464–467 Pallister–Killian syndrome, 725–726 Angelman syndrome, 62, 64, 65 incontinentia pigmenti, 509–510 Phelan–McDermid syndrome, 322–325 ATR‐X syndrome, 94 inverted duplicated chromosome 15 syndrome, Prader–Willi syndrome, 744 Beckwith–Wiedemann syndrome, 127, 128, 524–525 Proteus syndrome, 767 129, 130, 132 Klinefelter syndrome, 552 PTEN hamartoma tumor syndrome, 782 fetal alcohol spectrum disorders, 409 Loeys–Dietz syndrome, 573 Robin sequence, 815–816 Prader–Willi syndrome, 740, 741 Marfan syndrome, 592 Rubinstein–Taybi syndrome, 826–832 Silver–Russell syndrome, 841 myotonic dystrophy type 1, 622 Silver–Russell syndrome, 845 Sotos syndrome, 899 Noonan syndrome, 663 Smith–Lemli–Opitz syndrome, 856–857 DNA polymorphisms, Angelman syndrome, 64 Pallister–Killian syndrome, 728 Smith–Magenis syndrome, 865, Dolichocephaly: Phelan–McDermid syndrome, 329–330 872–878 craniosynostosis syndromes, 241 Prader–Willi syndrome, 755–756 Sotos syndrome, 905–907 oculo‐auriculo‐vertebral spectrum, 675 Proteus syndrome, 770–771 Stickler syndrome, 920 Sotos syndrome, 896 Rubinstein–Taybi syndrome, 830–831 Treacher Collins syndrome, 930–931 Dolichostenomelia, Marfan syndrome, 586 Smith–Lemli–Opitz syndrome, 860 trisomy 13 and 18 syndromes, 946–947 Down syndrome, 355–385 Smith–Magenis syndrome, 887–888 tuberous sclerosis complex, 964–965 and Alzheimer disease, 359, 365, 380 tuberous sclerosis complex, 968–969 Turner syndrome, 985–987 cardiovascular anomalies, 368–370 Turner syndrome, 990 VATER/VACTERL association, 998–999 comorbid conditions, 364–365 Williams syndrome, 1032 von Hippel–Lindau syndrome, 1009–1010 craniofacial anomalies, 383 Wolf–Hirschhorn syndrome, 275 Williams syndrome, 1025–1028 dental anomalies, 377–378 Dermatosporaxis Ehlers‐Danlos syndrome, Wolf–Hirschhorn syndrome, 270–271 dermatologic anomalies, 378 397–398 WT1‐related disorders, 344–345 development and behavior problems, 363–366 Development difficulties: DFNA6 gene mutation, Wolf–Hirschhorn diagnostic criteria, 356–358 Aarskog syndrome, 5 syndrome, 268 diagnostic testing, 359–361 achondroplasia, 16–17 DHCR7 gene mutation, Smith–Lemli–Opitz differential diagnosis, 361 Alagille syndrome, 35, 36 syndrome, 852, 853 Pallister–Killian syndrome, 722 albinism, 50 Diabetes insipidus, holoprosencephaly, 497, 501 Smith–Magenis syndrome, 871

0004944829.INDD 1047 9/25/2020 7:13:42 AM 1048 INDEX

Down syndrome (cont’d) Stickler syndrome, 921, 922 incidence, 389 ear anomalies, 371–372 Treacher Collins syndrome, 932–933 kyphoscoliotic EDS endocrine anomalies, 370–371 trisomy 13 and 18 syndromes, 951 diagnostic criteria, 398 etiology, pathogenesis, and genetics, 358–359 Turner syndrome, 989 diagnostic testing, 398 family adjustment, 367–368 Williams syndrome, 1032 differential diagnosis, 398 gastrointestinal anomalies, 375–376 Wolf–Hirschhorn syndrome, 273–274 etiology, pathogenesis, and genetics, 398 genetic counseling, 360–361 WT1‐related disorders, 345 manifestations and management, 398–399 growth and feeding problems, 361–363 Eating disorders: musculocontractural EDS hearing disorders, 371–372 Prader–Willi syndrome, 737, 746, 747 diagnostic criteria, 400–401 immunologic conditions, 379–381 Smith–Magenis syndrome, 867 diagnostic testing, 401 incidence, 355–356 Ectodermal dysplasia: differential diagnosis, 401 life expectancy, 355–356 incontinentia pigmenti, 508 etiology, pathogenesis, and genetics, 401 manifestations and management, 361–384 Phelan–McDermid syndrome, 329 manifestations and management, 401 mortality rate, 356 Ectopia lentis, Marfan syndrome, 578, 581, myopathic EDS musculoskeletal anomalies, 373–375 586, 590 diagnostic criteria, 401 neoplasia incidence, 381–383 Ectopic calcification, Gorlin syndrome, 471 diagnostic testing, 401 neurological anomalies, 380–381 Edwards syndrome. See Trisomy 18 syndrome differential diagnosis, 401 ophthalmologic anomalies, 372–373 Ehlers–Danlos syndromes, 389–403 etiology, pathogenesis, and genetics, 401 pulmonary hypertension, 369 arthrochalsia EDS periodontal EDS sexual maturation, 370–371 diagnostic criteria, 396–397 diagnostic criteria, 401–402 sleep abnormalities, 376–377 differential diagnosis, 397 diagnostic testing, 402 urogenital anomalies, 383–384 etiology, pathogenesis, and genetics, 397 differential diagnosis, 402 Drooling, ATR‐X syndrome, 100 manifestations and management, 397 etiology, pathogenesis, and genetics, 402 Duane retraction “syndrome”: brittle cornea syndrome manifestations and management, 402 Bardet–Biedl syndrome, 114 diagnostic criteria, 399 spondylodysplastic EDS oculo‐auriculo‐vertebral spectrum, 677 diagnostic testing, 399 diagnostic criteria, 399–400 Dubowitz syndrome, differential diagnosis, fetal differential diagnosis, 399 diagnostic testing, 400 alcohol spectrum disorders, 411 etiology, pathogenesis, and genetics, 399 differential diagnosis, 400 Duplication 3q syndrome, differential diagnosis, manifestations and management, 399 etiology, pathogenesis, and genetics, 400 Cornelia de Lange syndrome, 212 cardiac‐valvular EDS manifestations and management, 400 Dural ectasia, Marfan syndrome, 578 diagnostic criteria, 393 vascular EDS Dwarfing disorders, achondroplasia, 26 diagnostic testing, 393 diagnostic criteria, 394 Dysgerminoma, WAGR and Frasier differential diagnosis, 393 diagnostic testing, 394 syndrome, 349 etiology, pathogenesis, and genetics, 393 differential diagnosis, 394–395 Dysphagia: manifestations and management, 393 etiology, pathogenesis, and genetics, 394 CHARGE syndrome, 159 classical type manifestations and management, 395 myotonic dystrophy type 1, 617, 620 diagnostic criteria, 390–392 Elastin (ELN) gene mutations, Williams Prader–Willi syndrome, 754 diagnostic testing, 392 syndrome, 1022–1023, 1030 Dystonia, holoprosencephaly, 496 differential diagnosis, 392 Elbow hypermobility: etiology, pathogenesis, and genetics, 392 achondroplasia, 25 E6‐associated protein (E6AP), Angelman manifestations and management, 392 Cohen syndrome, 203 syndrome, 63 classic‐like EDS Ehlers–Danlos syndromes, 389 Ears, anomalies of: diagnostic criteria, 392–393 Elephant man disease. See Proteus syndrome: achondroplasia, 21 diagnostic testing, 393 Ellis–van Creveld syndrome, differential arthrogryposis, 88 differential diagnosis, 393 diagnosis, Pallister–Hall syndrome, 710 ATR‐X syndrome, 102 etiology, pathogenesis, and genetics, 393 Encopresis, Smith–Magenis syndrome, 874, 885 Bardet–Biedl syndrome, 117–118 manifestations and management, 393 Endocrine anomalies: CHARGE syndrome, 158–159, 165–166 dermatosporaxis EDS Alagille syndrome, 36 Coffin–Lowry syndrome, 180 diagnostic criteria, 397 Bardet–Biedl syndrome, 117 Cornelia de Lange syndrome, 215–216 diagnostic testing, 397 Beckwith–Wiedemann syndrome, 135–136 deletion 1p36 syndrome, 259 differential diagnosis, 397–398 Cohen syndrome, 202 deletion 5p syndrome, 285–286 etiology, pathogenesis, and genetics, 397 Costello syndrome, 235 deletion 22q11.2 syndrome, 307 manifestations and management, 398 deletion 1p36 syndrome, 260–261 Down syndrome, 371–372 diagnostic criteria, 389–390 deletion 22q11.2 syndrome, 306 fetal alcohol spectrum disorders, 416 differential diagnosis Down syndrome, 370–371 holoprosencephaly, 500 Kabuki syndrome, 531 49,XXXXY syndrome, 557 Kabuki syndrome, 534–535 Loeys–Dietz syndrome, 568 fragile X syndrome, 453 Mowat–Wilson syndrome, 605 Marfan syndrome, 585 holoprosencephaly, 497–498 myotonic dystrophy type 1, 622 Sotos syndrome, 901 inverted duplicated chromosome 15 Noonan syndrome, 663–664 hypermobile EDS syndrome, 524 oculo‐auriculo‐vertebral spectrum, 676–677 diagnostic criteria, 395 Kabuki syndrome, 534 osteogenesis imperfecta, 698–699 diagnostic testing, 395 Mowat–Wilson syndrome, 605 Pallister–Killian syndrome, 729–730 differential diagnosis, 395–396 myotonic dystrophy type 1, 623 Phelan–McDermid syndrome, 327 etiology, pathogenesis, and genetics, 395 Pallister–Hall syndrome, 711–712 Rett syndrome, 804 manifestations and management, 396 Prader–Willi syndrome, 750–752

0004944829.INDD 1048 9/25/2020 7:13:42 AM INDEX 1049

Smith–Magenis syndrome, 886–887 Coffin–Siris syndrome, 185 Rett syndrome, 792 Turner syndrome, 987–988 Cohen syndrome, 197, 198 Sotos syndrome, 907 Williams syndrome, 1029–1030 Cornelia de Lange syndrome, 208 Feeding difficulties: Endoglin (ENG) gene mutation, hereditary Costello syndrome, 226 achondroplasia, 12–16 hemorrhagic telangiectasia, 476 craniosynostosis syndromes, 241 Alagille syndrome, 36 Endolymphatic sac tumors, von Hippel–Lindau deletion 1p36 syndrome, 253, 256 Angelman syndrome, 66 syndrome, 1011, 1014 deletion 22q11.2 syndrome, 292 arthrogryposis, 84 Endometrial cancer, PTEN hamartoma tumor Down syndrome, 383 ATR‐X syndrome, 98 syndrome, 784 Ehlers–Danlos syndromes, vascular‐type Bardet–Biedl syndrome, 112–113 Enuresis: Ehlers‐Danlos syndrome, 241 Beckwith–Wiedemann syndrome, 134 fragile X syndrome, 452 fetal alcohol spectrum disorders, 410 cardio‐facio‐cutaneous syndrome, 150 Smith–Magenis syndrome, 874, 885 fetal hydantoin syndrome, 428 CHARGE syndrome, 161 Williams syndrome, 1033 fetal valproate syndrome, 429 Coffin–Lowry syndrome, 175 EP300 gene mutations, Rubinstein–Taybi Gorlin syndrome, 462, 464 Coffin–Siris syndrome, 188 syndrome, 826 holoprosencephaly, 489, 497 Cohen syndrome, 200 Epilepsy. See also Seizure disorders Kabuki syndrome, 529 Cornelia de Lange syndrome, 213 fetal alcohol spectrum disorders, 418 Mowat–Wilson syndrome, 599 Costello syndrome, 231 fetal anticonvulsant syndrome, 425 Noonan syndrome, 651 craniosynostosis syndromes, 246–247 inverted duplicated chromosome 15 syndrome, oculo‐auriculo‐vertebral spectrum, 671, deletion 1p36 syndrome, 256 515, 522 675, 677 deletion 5p syndrome, 283 Pallister–Killian syndrome, 718 Pallister–Killian syndrome, 718 deletion 22q11.2 syndrome, 298–300 Rett syndrome, 800, 801 Phelan–McDermid syndrome, 318 Denys–Drash syndrome, 343–344 tuberous sclerosis complex, 966 Prader–Willi syndrome, 737 Down syndrome, 361–363 Wolf–Hirschhorn syndrome, 268 Rubinstein–Taybi syndrome, 823–824 49,XXXXY syndrome, 558 Epileptic encephalopathy, infant and childhood, Smith–Lemli–Opitz syndrome, 852 fetal alcohol spectrum disorders, 413 Rett syndrome, 797 Smith–Magenis syndrome, 865 fetal anticonvulsant syndrome, Epiphysiodesis: Sotos syndrome, 895–897 434–435 Beckwith–Wiedemann syndrome, 134 Treacher Collins syndrome, 927, 931–932 fragile X syndrome, 447 Proteus syndrome, 767 trisomy 13 syndrome, 942 Gorlin syndrome, 463 Episodic gastric pseudovolvulus, ATR‐X Williams syndrome, 1021 hereditary hemorrhagic telangiectasia, 478 syndrome, 100 Wolf–Hirschhorn syndrome, 265, 268, 270 holoprosencephaly, 494–495 Epistaxis, hereditary hemorrhagic telangiectasia, Facial–genital–digital syndrome. See Aarskog incontinentia pigmenti, 509 478–479 syndrome inverted duplicated chromosome 15 Epithelial follicular neoplasias, differential Faciogenital dysplasia. See Aarskog syndrome syndrome, 519 diagnosis, PTEN hamartoma tumor Factor XI deficiency, Noonan syndrome, 660 Kabuki syndrome, 532 syndrome, 781 Factor XII deficiency, Noonan syndrome, 660 Klinefelter syndrome, 542–543 Escobar syndrome, arthrogryposis, 87 Failure‐to‐thrive: Loeys–Dietz syndrome, 569 Esophageal atresia, VATER/VACTERL achondroplasia, 20 Marfan syndrome, 586–587 association, 1000 Alagille syndrome, 36 Mowat–Wilson syndrome, 601–602 Esotropia: Angelman syndrome, 66 myotonic dystrophy type 1, 617 arthrogryposis, 87 Cohen syndrome, 200 neurofibromatosis type 1, 636–637 cardio‐facio‐cutaneous syndrome, 152 Down syndrome, 362 Noonan syndrome, 655–656 Down syndrome, 373 fetal alcohol spectrum disorders, 413 oculo‐auriculo‐vertebral spectrum, 674 Estrogen treatment: holoprosencephaly, 494–495 osteogenesis imperfecta, 694–695 Prader–Willi syndrome, 752 incontinentia pigmenti, 509 Pallister–Hall syndrome, 710 Turner syndrome, 984, 988 Loeys–Dietz syndrome, 569 Pallister–Killian syndrome, 724–725 Exotropia, cardio‐facio‐cutaneous syndrome, 152 Prader–Willi syndrome, 742 Phelan–McDermid syndrome, 322 Extended limb lengthening, and Silver–Russell syndrome, 843 Prader–Willi syndrome, 742–744 achondroplasia, 12 Smith–Magenis syndrome, 871 Proteus syndrome, 766–767 Extrahepatic disorders, differential diagnosis, Falx cerebri calcification, Gorlin syndrome, PTEN hamartoma tumor syndrome, 782 Alagille syndrome, 35 460, 472 Rett syndrome, 798–799 Eye anomalies. See Ophthalmologic anomalies Familial adenomatous polyposis, differential Robin sequence, 814–815 Eye contact, Rett syndrome, 799 diagnosis, PTEN hamartoma tumor Rubinstein–Taybi syndrome, 826–827 syndrome, 781 Silver–Russell syndrome, 843–844 Facial angiofibroma, differential diagnosis, Familial cholestatic liver disease, Alagille Smith–Lemli–Opitz syndrome, 855–856 tuberous sclerosis complex, 963 syndrome, 31 Smith–Magenis syndrome, 871–872 Facial angiofibromas, tuberous sclerosis complex, Fanconi anemia: Sotos syndrome, 901–905 958, 968 differential diagnosis, VATER/VACTERL Stickler syndrome, 920 Facial anomalies: association, 997 Treacher Collins syndrome, 930 Aarskog syndrome, 1–2 Wilms tumor, 343 trisomy 13 and 18 syndromes, 945–946 achondroplasia, 26 FBN1 gene mutations, Marfan syndrome, 577, tuberous sclerosis complex, 964 Alagille syndrome, 32 578, 580 Turner syndrome, 980–981 cardio‐facio‐cutaneous syndrome, 147 FBN2 gene mutations, Loeys–Dietz VATER/VACTERL association, 998 CHARGE syndrome, 159 syndrome, 568 von Hippel–Lindau syndrome, 1009 Coffin–Lowry syndrome, 171, 172 Febrile convulsions: WAGR syndrome, 343–344

0004944829.INDD 1049 9/25/2020 7:13:42 AM 1050 INDEX

Feeding difficulties: (cont’d) hematologic anomalies, 438 Williams syndrome, 1021, 1023 Williams syndrome, 1024–1025 manifestations and management, 434 Wolf–Hirschhorn syndrome, 269 Wolf–Hirschhorn syndrome, 270 musculoskeletal anomalies, 437–438 FMR1 gene mutation: WT1‐related disorders, 343–344 neoplasia incidence, 438 fragile X syndrome, 445 Fertility problems: neurological anomalies, 436 Klinefelter syndrome, 542 Klinefelter syndrome, 548–549 ophthalmologic anomalies, 437 FMRP protein, fragile X syndrome, 444 myotonic dystrophy type 1, 623 Fetal hydantoin syndrome, 428–429, 434 Follicle‐stimulating hormone, Klinefelter Noonan syndrome, 662 Fetal valproate syndrome, 429–431 syndrome, 548 Prader–Willi syndrome, 751 Α‐fetoprotein (AFP), Beckwith–Wiedemann Folliculin gene (FLCN), Smith–Magenis Sotos syndrome, 900 syndrome, 139 syndrome, 869 Turner syndrome, 984–985 FGD1 gene, Aarskog syndrome, 1, 3, 4 Food allergies, Loeys–Dietz syndrome, 573 Fetal akinesia deformation sequence: FGFRL1 gene, Wolf–Hirschhorn syndrome, 268 Food aversion, Rett syndrome, 798 arthrogryposis, 76 FG syndrome, differential diagnosis, Williams Food‐seeking behavior: differential diagnosis, trisomy 18 syndrome, syndrome, 1024 Prader–Willi syndrome, 737 941 Fibrillin‐1 (FBN1) gene, Marfan syndrome, Smith–Magenis syndrome, 872 Fetal alcohol spectrum disorders, 405–424 577, 580 Foot anomalies. See also Clubfeet cardiovascular anomalies, 416–417 Fibroblast growth factor receptor 1 (FGFR1) ATR‐X syndrome, 102 CoFASP Consensus Clinical Diagnostic mutation, holoprosencephaly, 492, 493 Cornelia de Lange syndrome, 209 Guidelines, 406 Fibroblast growth factor receptor 2 (FGFR2) Costello syndrome, 234 dental anomalies, 416 mutation, Apert syndrome, 245 craniosynostosis syndromes, 243 development and behavior problems, 413–415 Fibroblast growth factor receptor 3 (FGFR3) deletion 1p36 syndrome, 260 diagnostic criteria, 406 mutation: Ehlers–Danlos syndromes, 392, 393, 401 diagnostic testing, 409–411 achondroplasia, 10–11, 26 inverted duplicated chromosome 15 syndrome, differential diagnosis, 411 craniosynostosis syndromes, 243 524 Cornelia de Lange syndrome, 212 thanatophoric dysplasia, 246 Marfan syndrome, 588 fetal anticonvulsant syndrome, 428 Fibromas: myotonic dystrophy type 1, 622 ear anomalies, 416 Gorlin syndrome, 460, 462, 469, 470, 471 Pallister–Killian syndrome, 713 etiology, pathogenesis, and genetics, 406–409 myotonic dystrophy type 1, 622 Rett syndrome, 802 gastrointestinal and hepatic anomalies, 417 neurofibromatosis type 1, 635 Silver–Russell syndrome, 845 genitourinary anomalies, 417 PTEN hamartoma tumor syndrome, 776, 785 Smith–Lemli–Opitz syndrome, 860 growth and feeding problems, 413 tuberous sclerosis complex, 958, 968, 969, 972 Sotos syndrome, 910, 911 hearing disorders, 416 Fibrous cephalic plaques, tuberous sclerosis trisomy 18 syndrome, 952 incidence and prevalence, 405–406 complex, 968 Wolf–Hirschhorn syndrome, 274 manifestations and management, 413–419 Fingernails: Foramen magnum, achondroplasia, 18 musculoskeletal anomalies, 417 Phelan–McDermid syndrome, 329 46,XY/47,XXY mosaicism, 552 neurological anomalies, 417–418 tuberous sclerosis complex, 958 48,XXXY syndrome, 553–556 ophthalmologic anomalies, 415–416 Flat feet, Loeys–Dietz syndrome, 570 48,XXYY syndrome, 552–553 societal implications and prevention, 418–419 FLCN gene mutations, Birt–Hogg–Dube 49,XXXXY syndrome, 556–559 Fetal alcohol syndrome: syndrome, 869 development and behavior problems, 557 cardiovascular anomalies, 416 FLNA mutation carriers, differential diagnosis, endocrine anomalies, 557 dental anomalies, 416 Loeys–Dietz syndrome, 569 immunologic conditions, 557 development and behavior problems, 415 Floating Harbor syndrome: musculoskeletal anomalies, 557 differential diagnosis, Williams differential diagnosis, Cornelia de Lange neurological anomalies, 556–557 syndrome, 1024 syndrome, 212, 213 Foveal hypoplasia, in albinism, 50, 52 ear anomalies, 416 Fluorescence in situ hybridization (FISH): FOXG1 gene mutation, Rett syndrome, 794 gastrointestinal and hepatic anomalies, 417 Alagille syndrome, 35 Fragile X‐associated primary ovarian hearing disorders, 416 Angelman syndrome, 65 insufficiency (FXPOI), 453 incidence and prevalence, 405 deletion 1p36 syndrome, 255 Fragile X‐associated tremor/ataxia syndrome renal anomalies, 417 Denys–Drash syndrome, 342 (FXTAS), 445, 450 Robin sequence, 810 Down syndrome, 360 Fragile X syndrome, 443–457 societal implications and prevention, 418 holoprosencephaly, 492 cardiovascular anomalies, 451 Fetal aminopterin syndrome, Robin inverted duplicated chromosome 15 syndrome, craniofacial anomalies, 450–451 sequence, 811 518 development and behavior problems, 447–449 Fetal anticonvulsant syndrome, 425–442 Klinefelter syndrome, 541 diagnostic criteria, 444 cardiovascular anomalies, 436 Pallister–Killian syndrome, 722 diagnostic testing, 446 craniofacial anomalies, 436–437 Phelan–McDermid syndrome, 317, 321 differential diagnosis, 446 development and behavior Prader–Willi syndrome, 740 Coffin–Lowry syndrome, 175 problems, 435 Robin sequence, 813 Klinefelter syndrome, 541–542 diagnostic criteria, 426 Rubinstein–Taybi syndrome, 825, 826 Smith–Magenis syndrome, 871 diagnostic testing, 427–428 Smith–Magenis syndrome, 863, 870 Sotos syndrome, 901 differential diagnosis, 428–434 trisomy 13 syndrome, 943 Williams syndrome, 1024 etiology, pathogenesis, and genetics, 426–427 trisomy 18 syndrome, 940 endocrine anomalies, 453 gastrointestinal anomalies, 437 Turner syndrome, 978 etiology, pathogenesis, and genetics, 444–446 genitourinary anomalies, 437 velo‐cardio‐facial syndrome, 291, 295 genetic counseling, 445–446 growth and feeding problems, 434–435 WAGR syndrome, 342 genitourinary anomalies, 452

0004944829.INDD 1050 9/25/2020 7:13:42 AM INDEX 1051

growth and feeding problems, 447 Coffin–Siris syndrome, 191 tuberous sclerosis complex, 962–963 manifestations and management, 446 Cornelia de Lange syndrome, 218 WT1‐related disorders, 342 musculoskeletal anomalies, 452–453 deletion 1p36 syndrome, 260 Genetic heterogeneity: neurological anomalies, 449–450 Down syndrome, 375–376 Aarskog syndrome, 1, 4 ophthalmologic anomalies, 450 fetal alcohol spectrum disorders, 417 Bardet–Biedl syndrome, 108 Frasier syndrome, 335 fetal anticonvulsant syndrome, 437 Beckwith–Wiedemann syndrome, 127 diagnostic criteria, 336–337 Gorlin syndrome, 471 Coffin–Lowry syndrome, 174 diagnostic testing, 341–342 hereditary hemorrhagic telangiectasia, Cohen syndrome, 196 differential diagnosis, 342–343 482–483 Ehlers–Danlos syndromes, 398, 399, 400 etiology, pathogenesis, and genetics, 339 holoprosencephaly, 500 Loeys–Dietz syndrome, 567 genitourinary anomalies, 346 Kabuki syndrome, 535–536 Stickler syndrome, 918, 919 incidence, 335 Mowat–Wilson syndrome, 603 Genitourinary anomalies: manifestations and management, 343–349 myotonic dystrophy type 1, 619–620 Aarskog syndrome, 2 neoplasia incidence, 348 Pallister–Hall syndrome, 712 Alagille syndrome, 40 Freeman‐Sheldon syndrome, differential Pallister–Killian syndrome, 727 ATR‐X syndrome, 101–102 diagnosis, musculocontractural EDS, 401 Phelan–McDermid syndrome, 329 Bardet–Biedl syndrome, 115–117 FRMD7 gene mutations, albinism, 49 Proteus syndrome, 769 Beckwith–Wiedemann syndrome, 137 Fryns syndrome, differential diagnosis: PTEN hamartoma tumor syndrome, 784, 785 cardio‐facio‐cutaneous syndrome, 152 Cornelia de Lange syndrome, 212 Rett syndrome, 803 CHARGE syndrome, 158, 166 Pallister–Killian syndrome, 724 Rubinstein–Taybi syndrome, 828–829 Coffin–Siris syndrome, 191 Silver–Russell syndrome, 844 Cornelia de Lange syndrome, 218–219 Gabapentin, Phelan–McDermid syndrome, 325 Smith–Lemli–Opitz syndrome, 858–859 craniosynostosis syndromes, 250 GABRB3 gene, inverted duplicated chromosome Smith–Magenis syndrome, 885 deletion 1p36 syndrome, 260 15 syndrome, 517 Sotos syndrome, 911 deletion 5p syndrome, 285 Gait disorders: Turner syndrome, 988–989 deletion 22q11.2 syndrome, 306 achondroplasia, 24 VATER/VACTERL association, 1000–1001 Down syndrome, 383–384 Angelman syndrome, 69 von Hippel–Lindau syndrome, 1014–1015 fetal alcohol spectrum disorders, 417 Down syndrome, 373 Williams syndrome, 1025, 1031 fetal anticonvulsant syndrome, 437 Mowat–Wilson syndrome, 604 Wolf–Hirschhorn syndrome, 275 fragile X syndrome, 452 Williams syndrome, 1033 GATA1 mutations, Down syndrome, 381 Gorlin syndrome, 470–471 Galloway–Mowat syndrome, differential diagnosis, GATA6 mutations, Pallister–Killian Kabuki syndrome, 536 WT1‐related disorders, 343 syndrome, 721 Mowat–Wilson syndrome, 604–605 Gamma‐glutamyl transferase, Alagille Generalized essential telangiectasia, differential Noonan syndrome, 662 syndrome, 35 diagnosis, hereditary hemorrhagic oculo‐auriculo‐vertebral spectrum, 678 Gastroenterology: telangiectasia, 478 osteogenesis imperfecta, 701 cardio‐facio‐cutaneous syndrome, 150–151 Generalized hypertrichosis, Cornelia de Lange Pallister–Hall syndrome, 712 deletion 5p syndrome, 286–287 syndrome, 220 Pallister–Killian syndrome, 728 Wolf–Hirschhorn syndrome, 275 Generalized hypotonia. See Hypotonia Phelan–McDermid syndrome, 330–331 Gastroesophageal reflux: Generalized overgrowth disorders, differential Prader–Willi syndrome, 750 ATR‐X syndrome, 100 diagnosis, Sotos syndrome, 901 Proteus syndrome, 770 CHARGE syndrome, 158 Genetic counseling: Rubinstein–Taybi syndrome, 831 Coffin–Siris syndrome, 191 Alagille syndrome, 35 Smith–Lemli–Opitz syndrome, Cornelia de Lange syndrome, 213, 218–219 Angelman syndrome, 65 859–860 deletion 1p36 syndrome, 256 ATR‐X syndrome, 97–98 Smith–Magenis syndrome, 885–886 inverted duplicated chromosome 15 syndrome, Bardet–Biedl syndrome, 111–112 Sotos syndrome, 909 519 deletion 5p syndrome, 282 trisomy 13 and 18 syndromes, 949–950 Mowat–Wilson syndrome, 603 deletion 22q11.2 syndrome, 294–295 tuberous sclerosis complex, 970–971 Pallister–Killian syndrome, 725 Down syndrome, 360–361 Turner syndrome, 987 Phelan–McDermid syndrome, 329 49,XXXXY syndrome, 557 VATER/VACTERL association, 1002 Rett syndrome, 798, 803 fragile X syndrome, 445–446 von Hippel–Lindau syndrome, 1015 Rubinstein–Taybi syndrome, 828, 829 Gorlin syndrome, 462 WAGR syndrome, 340 Silver–Russell syndrome, 844 holoprosencephaly, 494 Williams syndrome, 1032–1033 Smith–Lemli–Opitz syndrome, 855 Loeys–Dietz syndrome, 574 Wolf–Hirschhorn syndrome, 273 Smith–Magenis syndrome, 872 Mowat–Wilson syndrome, 600–601 WT1‐related disorders, 342, 346–348 Treacher Collins syndrome, 930 myotonic dystrophy type 1, 616–617 Genotype–phenotype correlations: trisomy 13 and 18 syndromes, 945, 946, 950 neurofibromatosis type 1, 633–634 Angelman syndrome, 64 Williams syndrome, 1031 Noonan syndrome, 654 ATR‐X syndrome, 95–96 Wolf–Hirschhorn syndrome, 270 oculo‐auriculo‐vertebral spectrum, 673 deletion 1p36 syndrome, 254 Gastrointestinal anomalies: osteogenesis imperfecta, 684, 692–693 Greig cephalopolysyndactyly syndrome, 709 Alagille syndrome, 36–38 Pallister–Killian syndrome, 721 Loeys–Dietz syndrome, 566 albinism, 55 Prader–Willi syndrome, 740 neurofibromatosis type 1, 633 ATR‐X syndrome, 100 Rett syndrome, 797 Noonan syndrome, 653 Bardet–Biedl syndrome, 118 Smith–Magenis syndrome, 870 osteogenesis imperfecta, 692 Beckwith–Wiedemann syndrome, 136–137 Sotos syndrome, 901 Smith–Lemli–Opitz syndrome, 852 Coffin–Lowry syndrome, 181 Stickler syndrome, 919 Sotos syndrome, 900

0004944829.INDD 1051 9/25/2020 7:13:42 AM 1052 INDEX

Genotype–phenotype correlations: (cont’d) diagnostic testing, 709–710 Rett syndrome, 798–799 tuberous sclerosis complex, 962 differential diagnosis, 710 Robin sequence, 814–815 velo‐cardio‐facial syndrome, 293 etiology, pathogenesis, and genetics, 708–709 Rubinstein–Taybi syndrome, 826–827 von Hippel–Lindau syndrome, 1005 incidence, 707 Silver–Russell syndrome, 842, 843–844 Wolf–Hirschhorn syndrome, 269 manifestations and management, 713–714 Smith–Lemli–Opitz syndrome, 855–856 WT1‐related disorders, 339 musculoskeletal anomalies, 714 Smith–Magenis syndrome, 871–872, 886 Genu valgus, Prader–Willi syndrome, 737 neurological anomalies, 713–714 Sotos syndrome, 901–905 Germ cell tumors: Growth hormone therapy: Stickler syndrome, 920 Beckwith–Wiedemann syndrome, 139 achondroplasia, 12 Treacher Collins syndrome, 930 Down syndrome, 382 Costello syndrome, 231 trisomy 13 and 18 syndromes, 945–946 Klinefelter syndrome, 551 Down syndrome, 364 tuberous sclerosis complex, 964 Pallister–Killian syndrome, 730 neurofibromatosis type 1, 636 Turner syndrome, 980–981 Rubinstein–Taybi syndrome, 832 Prader–Willi syndrome, 738–739, 742, 743, VATER/VACTERL association, 998 Ghent criteria, Marfan syndrome, 579 750, 753–754 von Hippel–Lindau syndrome, 1009 Gillespie syndrome, differential diagnosis, Silver–Russell syndrome, 843 WAGR syndrome, 343–344 WAGR syndrome, 342 Smith–Magenis syndrome, 880 Williams syndrome, 1024–1025 Gingival fibromas, tuberous sclerosis Turner syndrome, 980 Wolf–Hirschhorn syndrome, 270 complex, 972 Growth problems: WT1‐related disorders, 343–344 Glaucoma: Aarskog syndrome, 4–5 GTF2I gene mutation, Williams syndrome, 1023 aniridia, 345 achondroplasia, 12–16 Gynecomastia, Klinefelter syndrome, 548, 551 Marfan syndrome, 590 Alagille syndrome, 36 Phelan–McDermid syndrome, 327 albinism, 50 Hadju–Cheney syndrome, differential diagnosis, Rubinstein–Taybi syndrome, 829 Angelman syndrome, 66 Alagille syndrome, 36 Wolf–Hirschhorn syndrome, 274 arthrogryposis, 79–84 Hair anomalies, incontinentia pigmenti, 510 WT1‐related disorders, 345 ATR‐X syndrome, 98 Hair color: GLI3 gene mutation: Bardet–Biedl syndrome, 112–113 albinism, 51 Greig cephalopolysyndactyly syndrome, 709 Beckwith–Wiedemann syndrome, 134 Smith–Magenis syndrome, 887 Pallister–Hall syndrome, 707 cardio‐facio‐cutaneous syndrome, 150 Hairy elbow syndrome. See Wiedemann–Steiner Glioblastoma multiforme, Gorlin syndrome, 469 CHARGE syndrome, 158, 161 syndrome Glossoptosis, Robin sequence, 808 Coffin–Lowry syndrome, 175 Hamartomatous syndromes, differential Goldberg–Shprintzen syndrome, differential Coffin–Siris syndrome, 188 diagnosis, neurofibromatosis diagnosis, Mowat–Wilson syndrome, 601 Cohen syndrome, 200 type 1, 635 Goldenhar syndrome. See Oculo‐auriculo‐ Cornelia de Lange syndrome, 208–209, 213 Hand anomalies. See also Thumb anomalies vertebral spectrum Costello syndrome, 231 Aarskog syndrome, 2, 6 Goltz focal dermal hypoplasia, craniosynostosis syndromes, 246–247 Coffin–Lowry syndrome, 172 differential diagnosis, incontinentia deletion 1p36 syndrome, 256, 260 Cornelia de Lange syndrome, 209 pigmenti, 509 deletion 5p syndrome, 283 Costello syndrome, 233 Gonadoblastoma: deletion 22q11.2 syndrome, 298–300, 306 craniosynostosis syndromes, 241 Turner syndrome, 978, 990 Denys–Drash syndrome, 343–344 deletion 22q11.2 syndrome, 292 WT1‐related disorders, 343, 349 Down syndrome, 361–363 Down syndrome, 357 Gorlin syndrome, 459–474 fetal alcohol spectrum disorders, 411, 413 holoprosencephaly, 493 cardiovascular anomalies, 469–470 fetal anticonvulsant syndrome, 434–435 Kabuki syndrome, 530 craniofacial anomalies, 464 fragile X syndrome, 447 Marfan syndrome, 588 dental anomalies, 467–468 Gorlin syndrome, 463 Mowat–Wilson syndrome, 605 dermatologic anomalies, 464–467 hereditary hemorrhagic telangiectasia, 478 Pallister–Hall syndrome, 712 development and behavior problems, 464 holoprosencephaly, 494–495 Phelan–McDermid syndrome, 328 diagnostic criteria, 459–460 incontinentia pigmenti, 509 Proteus syndrome, 764 diagnostic testing, 462 inverted duplicated chromosome 15 syndrome, Rett syndrome, 799, 800 differential diagnosis, 462–463 519 Rubinstein–Taybi syndrome, 831 etiology, pathogenesis, and genetics, 460–462 Kabuki syndrome, 532 Silver–Russell syndrome, 845 gastrointestinal anomalies, 471 Klinefelter syndrome, 542–543 Smith–Lemli–Opitz syndrome, 860 genetic counseling, 462 Loeys–Dietz syndrome, 569 Smith–Magenis syndrome, 885 genitourinary anomalies, 470–471 Marfan syndrome, 586–587 trisomy 13 and 18 syndromes, 951 growth and feeding problems, 463 Mowat–Wilson syndrome, 601–602 Wolf–Hirschhorn syndrome, 274 incidence, 459 myotonic dystrophy type 1, 617 Hand‐licking, Smith–Magenis syndrome, 867 manifestations and management, 463–472 neurofibromatosis type 1, 636–637 Haploinsufficiency: musculoskeletal anomalies, 470 Noonan syndrome, 655–656 Alagille syndrome, 34 neoplasia incidence, 468–469 oculo‐auriculo‐vertebral spectrum, 674 craniosynostosis syndromes, 246 ophthalmologic anomalies, 469 osteogenesis imperfecta, 694–695 deletion 1p36 syndrome, 255 GPR143 gene mutations, albinism, 49 Pallister–Hall syndrome, 710 Denys–Drash syndrome, 339 “Greek warrior helmet appearance of the nose,” Pallister–Killian syndrome, 724–725 Ehlers–Danlos syndromes, 392, 393, 394 Wolf–Hirschhorn syndrome, 266 Phelan–McDermid syndrome, 322 Greig cephalopolysyndactyly syndrome, 709 Greig cephalopolysyndactyly syndrome, 707–716 Prader–Willi syndrome, 742–744 Loeys–Dietz syndrome, 566 development and behavior, 713 Proteus syndrome, 766–767 Marfan syndrome, 581 diagnostic criteria, 708 PTEN hamartoma tumor syndrome, 782 Mowat–Wilson syndrome, 598

0004944829.INDD 1052 9/25/2020 7:13:42 AM INDEX 1053

Pallister–Killian syndrome, 721 diagnostic criteria, 127 development and behavior problems, 495–497 Phelan–McDermid syndrome, 317, 320 diagnostic testing, 132–133 diagnostic criteria, 488–489 Rett syndrome, 797 differential diagnosis, 133 diagnostic testing, 493–494 Smith–Magenis syndrome, 863, 867, 869, 870 Proteus syndrome, 766 differential diagnosis, 494 Treacher Collins syndrome, 929 etiology, pathogenesis, and genetics, 131, 132 Pallister–Hall syndrome, 710 Turner syndrome, 978 α‐fetoprotein (AFP), 139 trisomy 13 syndrome, 943 velo‐cardio‐facial syndrome, 293 incidence, 125–126 ear anomalies, 500 Wolf–Hirschhorn syndrome, 268 neoplasia incidence, 137–139 endocrine anomalies, 497–498 Hearing disorders: Pallister–Killian syndrome, 725 etiology, pathogenesis, and genetics, 489–493 achondroplasia, 21 Hemihypertrophy. See Hemihyperplasia gastrointestinal anomalies, 500 Alagille syndrome, 35 Hemoglobin H, ATR‐X syndrome, 96 genetic counseling, 494 albinism, 48 Hepatic anomalies: growth and feeding problems, 494–495 arthrogryposis, 88 Alagille syndrome, 32 hearing disorders, 500 ATR‐X syndrome, 102 fetal alcohol spectrum disorders, 417 immunologic conditions, 500–501 Bardet–Biedl syndrome, 117–118 tuberous sclerosis complex, 972 incidence, 487–488 CHARGE syndrome, 158, 162, 165–166 Wolf–Hirschhorn syndrome, 276 manifestations and management, 494–501 Coffin–Lowry syndrome, 177, 180 Hepatoblastoma: neurological anomalies, 498–500 Coffin–Siris syndrome, 191 Beckwith–Wiedemann syndrome, 138 ophthalmologic anomalies, 500 Cornelia de Lange syndrome, 215–216 trisomy 18 syndrome, 950 Smith–Lemli–Opitz syndrome, 857 deletion 1p36 syndrome, 259 Hepatomegaly, Alagille syndrome, 37 trisomy 13 syndrome, 942, 943, 947 deletion 5p syndrome, 285–286 Hereditary benign telangiectasia, 478 Holt–Oram syndrome, differential diagnosis, deletion 22q11.2 syndrome, 307 Hereditary hemorrhagic telangiectasia, 475–486 Pallister–Hall syndrome, 710 Down syndrome, 371–372 development and behavior problems, 478 Holzgreve syndrome, differential diagnosis, fetal alcohol spectrum disorders, 416 diagnostic criteria, 475 Pallister–Hall syndrome, 710 holoprosencephaly, 500 diagnostic testing, 477 Homocystinuria, differential diagnosis, Marfan Kabuki syndrome, 534–535 differential diagnosis, 477–478 syndrome, 586 Mowat–Wilson syndrome, 605 etiology, pathogenesis, and genetics, 476–477 Homozygous achondroplasia, 11, 26 Muenke syndrome, 248 gastrointestinal anomalies, 482–483 Hormone replacement therapy: myotonic dystrophy type 1, 622 growth and feeding problems, 478 Prader–Willi syndrome, 752 Noonan syndrome, 663–664 immunologic conditions, 484 Turner syndrome, 984 oculo‐auriculo‐vertebral spectrum, 676–677 incidence, 475 HPS1 gene, Hermansky–Pudlak syndrome, 49 osteogenesis imperfecta, 698–699 manifestations and management, 478–484 HRAS gene mutations, Costello syndrome, 226 Pallister–Killian syndrome, 729–730 neurological anomalies, 481–482 Hugging behavior, Smith–Magenis syndrome, Phelan–McDermid syndrome, 327 ophthalmologic anomalies, 483–484 867, 874 Proteus syndrome, 770 otorhinolaryngologic anomalies, 478–479 Human chorionic gonadotropin: Rett syndrome, 804 respiratory anomalies, 479–481 Prader–Willi syndrome, 751 Smith–Magenis syndrome, 867, 870, 873, 881 Hereditary progressive arthroophthalmopathy. See trisomy 18 syndrome, 941 Sotos syndrome, 908 Stickler syndrome: Hydrocephalus: Stickler syndrome, 918, 921, 922 Hermansky–Pudlak syndrome, 45 achondroplasia, 17–18 Treacher Collins syndrome, 933 dermatologic anomalies, 51–52 Greig cephalopolysyndactyly syndrome, trisomy 13 and 18 syndromes, 951 diagnostic criteria, 47 713, 714 Turner syndrome, 989 diagnostic testing, 49 Hyperactivity: Williams syndrome, 1032 etiology, pathogenesis, and genetics, 47 Aarskog syndrome, 5 Wolf–Hirschhorn syndrome, 268–269, gastrointestinal anomalies, 55 Angelman syndrome, 67–68 273–274 hematologic anomalies, 53–54 deletion 5p syndrome, 284 WT1‐related disorders, 345 incidence, 46 fragile X syndrome, 447 Heart defects. See Cardiovascular anomalies ophthalmologic anomalies, 53 Hyperacusis: Helicobacter pylori infection, Down pulmonary anomalies, 54 deletion 5p syndrome, 286 syndrome, 375 Hernias: Smith–Magenis syndrome, 881 Helsmoortel–Van der Aa syndrome, differential Marfan syndrome, 592 Hypercalcemia, Williams syndrome, 1029, 1031 diagnosis, deletion 1p36 syndrome, 256 Proteus syndrome, 770 Hypercalciuria, Williams syndrome, 1029 Hemangioblastomas, von Hippel–Lindau Williams syndrome, 1032 Hypercholesterolemia: syndrome, 1006, 1007–1008, 1010, Herpes, differential diagnosis, incontinentia Alagille syndrome, 32, 37 1012–1013 pigmenti, 509 Smith–Magenis syndrome, 870, 885 Hematologic disorders: Hip dysplasia: Hyperextensible joints. See Joint laxity albinism, 53–54 Prader–Willi syndrome, 755 Hypergammaglobulinemia, deletion 22q11.2 ATR‐X syndrome, 101 Smith–Lemli–Opitz syndrome, 860 syndrome, 305 cardio‐facio‐cutaneous syndrome, 153 Hirschsprung disease: Hypergonadotropic hypogonadism, Klinefelter Cornelia de Lange syndrome, 219–220 ATR‐X syndrome, 100 syndrome, 547–548 fetal anticonvulsant syndrome, 438 Down syndrome, 376 Hyperlipidemia: Noonan syndrome, 659–661 Mowat–Wilson syndrome, 597, 601, 603 Bardet–Biedl syndrome, 117 trisomy 13 and 18 syndromes, 950 Rubinstein–Taybi syndrome, 828 Beckwith–Wiedemann syndrome, 135 Hemihyperplasia, 125 Smith–Lemli–Opitz syndrome, 855, 859 Hyperlordosis, achondroplasia, 25 Beckwith–Wiedemann syndrome, 134 Holoprosencephaly, 487–503 Hypermenorrhagia, Rubinstein–Taybi development and behavior problems, 135 craniofacial anomalies, 497 syndrome, 831

0004944829.INDD 1053 9/25/2020 7:13:42 AM 1054 INDEX

Hypermetrorrhagia, Rubinstein–Taybi Hypoplasia: Immunoglobulin: syndrome, 831 cerebellar vermis, Bardet–Biedl syndrome, 118 deletion 22q11.2 syndrome, 305 Hyperopia: genital, Prader–Willi syndrome, 736 Smith–Magenis syndrome, 887 Phelan–McDermid syndrome, 327 Hypospadias: Immunologic conditions: Prader–Willi syndrome, 738 Rubinstein–Taybi syndrome, 831 CHARGE syndrome, 166–167 Turner syndrome, 989 Smith–Lemli–Opitz syndrome, 859, 860 Coffin–Siris syndrome, 191 Williams syndrome, 1032 Hypothalamic hamartoma, Pallister–Hall Cohen syndrome, 202 Hyperphagia: syndrome, 711 Cornelia de Lange syndrome, 219–220 Bardet–Biedl syndrome, 112 Hypothalamic‐pituitary function, CHARGE deletion 22q11.2 syndrome, 305–306 Prader–Willi syndrome, 746–749 syndrome, 166 Down syndrome, 379–381 Hyperphosphatasia with mental retardation‐1. See Hypothyroidism: 49,XXXXY syndrome, 557 Mabry syndrome Bardet–Biedl syndrome, 117 hereditary hemorrhagic telangiectasia, 484 Hyperreflexia, Cornelia de Lange syndrome, 219 Beckwith–Wiedemann syndrome, 135 holoprosencephaly, 500–501 Hypertension: deletion 1p36 syndrome, 260 incontinentia pigmenti, 512 Bardet–Biedl syndrome, 116 deletion 22q11.2 syndrome, 298, 306 Kabuki syndrome, 536 fragile X syndrome, 451 differential diagnosis, Down syndrome, 361 Klinefelter syndrome, 551–552 neurofibromatosis type 1, 645 Down syndrome, 371 Loeys–Dietz syndrome, 573 Phelan–McDermid syndrome, 328 Klinefelter syndrome, 549 Mowat–Wilson syndrome, 605–606 Turner syndrome, 983 Noonan syndrome, 664 Phelan–McDermid syndrome, 330 Williams syndrome, 1030 Phelan–McDermid syndrome, 323, 325 Rubinstein–Taybi syndrome, 828 Hyperthyroidism, deletion 22q11.2 Prader–Willi syndrome, 743 Smith–Magenis syndrome, 887 syndrome, 298 Williams syndrome, 1029, 1030 Turner syndrome, 987 Hypertonia: Hypotonia: Wolf–Hirschhorn syndrome, 275 Cornelia de Lange syndrome, 219 achondroplasia, 16 Imprinting: deletion 5p syndrome, 285 Angelman syndrome, 65 Angelman syndrome, 61, 62, 64 Pallister–Killian syndrome, 718 arthrogryposis, 75 Beckwith–Wiedemann syndrome, 127, trisomy 13 and 18 syndromes, 947 ATR‐X syndrome, 98 131–132 Williams syndrome, 1028 cardio‐facio‐cutaneous syndrome, 147 Prader–Willi syndrome, 739, 740 Hypertriglyceridemia, Alagille syndrome, 37 Coffin–Siris syndrome, 185 Silver–Russell syndrome, 839 Hypertrophic cardiomyopathy: Cohen syndrome, 202 Incontinence: cardio‐facio‐cutaneous syndrome, 151 Costello syndrome, 232 Mowat–Wilson syndrome, 603 Noonan syndrome, 657 deletion 1p36 syndrome, 258 myotonic dystrophy type 1, 620 Hypocalcemia: deletion 5p syndrome, 285, 286 Phelan–McDermid syndrome, 323 Beckwith–Wiedemann syndrome, 135 deletion 22q11.2 syndrome, 302 Incontinentia pigmenti, 505–514 deletion 22q11.2 syndrome, 306 Down syndrome, 356, 361 breast anomalies, 512 Hypocholesterolemia, Smith–Lemli–Opitz Ehlers–Danlos syndromes, 398 dental anomalies, 512 syndrome, 853 47,XXY syndrome, 543 dermatologic anomalies, 509–510 Hypochondroplasia, differential diagnosis, fragile X syndrome, 447 development and behavior problems, 509 achondroplasia, 11 inverted duplicated chromosome 15 syndrome, diagnostic criteria, 505–506 Hypogammaglobulinemia, deletion 22q11.2 518, 522 diagnostic testing, 508 syndrome, 305 myotonic dystrophy type 1, 612 differential diagnosis, 508–509 Hypogenitalism: Pallister–Killian syndrome, 718, etiology, pathogenesis, and genetics, 505–508 Bardet–Biedl syndrome, 107, 108, 116 726–727 growth and feeding problems, 509 Smith–Lemli–Opitz syndrome, 851, 854 Phelan–McDermid syndrome, 325 hair and nails, anomalies of, 510 Hypoglycemia: Prader–Willi syndrome, 742, 749 incidence, 505 Beckwith–Wiedemann syndrome, 136 Rett syndrome, 791 manifestations and management, 509–512 Costello syndrome, 235 Rubinstein–Taybi syndrome, 831 neurological anomalies, 511–512 Silver–Russell syndrome, 846 Silver–Russell syndrome, 844 ophthalmologic anomalies, 510–511 Sotos syndrome, 904 Smith–Magenis syndrome, 883 Induced pluripotent stem cells (IPSCs), Hypogonadism: Sotos syndrome, 905, 907 Angelman syndrome, 64 CHARGE syndrome, 166 trisomy 13 and 18 syndromes, 947 Infantile hypotonia. See Hypotonia Prader–Willi syndrome, 736, 750–751 Williams syndrome, 1028 Infantile neuronal ceroid lipofuscinosis (Batten Hypomelanosis of Ito, differential diagnosis, Wolf–Hirschhorn syndrome, 272 disease), differential diagnosis, Rett inverted duplicated chromosome 15 Hypoxemia, achondroplasia, 20 syndrome, 797 syndrome, 518 Hypoxia‐inducible factor, von Hippel–Lindau Inflammatory bowel disease, Turner Hypomelanotic macules, tuberous sclerosis syndrome, 1006 syndrome, 988 complex, 958 ING4 gene, Pallister–Killian syndrome, 720, 721 Hypoparathyroidism, deletion 22q11.2 Idiopathic hypercalcemia. See Williams Insulin‐like growth factor‐1 (IGF‐1): syndrome, 306 syndrome Beckwith–Wiedemann syndrome, 129 Hypophosphatasia, differential diagnosis, IGF2 gene mutation, Beckwith–Wiedemann Phelan–McDermid syndrome, 325 osteogenesis imperfecta, 693–694 syndrome, 133 Insulin therapy, Phelan–McDermid Hypopigmentation: IGFBP2 gene, Pallister–Killian syndrome, 721 syndrome, 325 albinism, 46 IKBKG gene, incontinentia pigmenti, 505, Integumentary. See Dermatologic anomalies Angelman syndrome, 64 507–508 Intellectual disabilities: tuberous sclerosis complex, 963, 968 Ilizarov technique, Proteus syndrome, 768 Aarskog syndrome, 5

0004944829.INDD 1054 9/25/2020 7:13:42 AM INDEX 1055

Apert syndrome, 247 IQ levels. See Cognitive function ear anomalies, 534–535 ATR‐X syndrome, 93 Ischemic heart disease, Turner syndrome, 982 endocrine anomalies, 534 CHARGE syndrome, 162 Isochromosome 12p, Pallister–Killian syndrome, etiology, pathogenesis, and genetics, 530–531 Coffin–Lowry syndrome, 171 718, 720 gastrointestinal anomalies, 535–536 Cohen syndrome, 195 Isodicentric 15 syndrome. See Inverted duplicated genitourinary anomalies, 536 Cornelia de Lange syndrome, 215 chromosome 15 syndrome growth and feeding problems, 532 deletion 1p36 syndrome, 257 Isolated hemihyperplasia. See Hemihyperplasia hearing disorders, 534–535 deletion 5p syndrome, 283 immunologic conditions, 536 Down syndrome, 363 Jackson–Weiss syndrome, craniosynostosis incidence, 529 fragile‐X syndrome, 443 syndromes, 243 manifestations and management, 532–536 inverted duplicated chromosome 15 syndrome, Jaffe–Campanacci syndrome, differential musculoskeletal anomalies, 536 515 diagnosis, neurofibromatosis neurological anomalies, 533 Kabuki syndrome, 529 type 1, 635 ophthalmologic anomalies, 534 Mowat–Wilson syndrome, 597 JAG1 gene mutation, Alagille syndrome, 31, 34, Kallmann syndrome: neurofibromatosis type 1, 637 35, 38 CHD7 mutations, 160 oculo‐auriculo‐vertebral spectrum, 674 Jaundice: differential diagnosis, Klinefelter Prader–Willi syndrome, 735 Alagille syndrome, 36 syndrome, 541 Rett syndrome, 791, 799 fetal alcohol spectrum disorders, 417 KDM6A gene mutations, Kabuki syndrome, Smith–Lemli–Opitz syndrome, 856 Sotos syndrome, 897, 904 530, 531 Smith–Magenis syndrome, 865, 872 Jaw anomalies: Keloids, Rubinstein–Taybi syndrome, 830, 831 tuberous sclerosis complex, 964 achondroplasia, 26 Keratoconus: Turner syndrome, 985 arthrogryposis, 85, 87 Angelman syndrome, 70 WAGR syndrome, 344 Gorlin syndrome, 467 Down syndrome, 373 Williams syndrome, 1022 Joint hypermobility. See Joint laxity Klinefelter syndrome, 539–562 Wolf–Hirschhorn syndrome, 271 Joint laxity: dermatologic anomalies, 552 Intention tremor, Sotos syndrome, 907 Aarskog syndrome, 6 development and behavior problems, 543–547 Interstitial pulmonary fibrosis, Hermansky– achondroplasia, 25 diagnostic criteria, 540 Pudlak syndrome, 54 Bardet–Biedl syndrome, 115 diagnostic testing, 541 Intracrancial anomalies, Cohen syndrome, 202 Cohen syndrome, 199, 202, 203 differential diagnosis, 541–542 Intracranial bleeding: Costello syndrome, 233 Sotos syndrome, 901 Alagille syndrome, 38–39 Ehlers–Danlos syndromes, 389, 390, 398 endocrine anomalies, 547–550 hereditary hemorrhagic telangiectasia, 481 fragile X syndrome, 452 etiology, pathogenesis, and genetics, 541 Intracranial hypotension syndrome, Marfan Kabuki syndrome, 533, 536 growth and feeding problems, syndrome, 591 Loeys–Dietz syndrome, 563 542–543 Intracranial lesions, tuberous sclerosis complex, Marfan syndrome, 587 immunologic conditions, 551–552 965–966 Pallister–Killian syndrome, 728 incidence, 539–540 Intracranial tumors, von Hippel–Lindau Rubinstein–Taybi syndrome, 831 incontinentia pigmenti, 507, 508 syndrome, 1010 Sotos syndrome, 910 language difficulties, 544 Intrahepatic cholestasis, Alagille syndrome, 31 Stickler syndrome, 922 manifestations and management, 542–559 Intrauterine growth retardation: Williams syndrome, 1033 musculoskeletal anomalies, 550–551 Cornelia de Lange syndrome, 212 Joubert syndrome: neoplasia incidence, 551 Marfan syndrome, 592 differential diagnosis, Bardet–Biedl neurological anomalies, 545–547 Silver–Russell syndrome, 837, 843 syndrome, 112 pulmonary anomalies, 552 trisomy 18 syndrome, 940 and Smith–Magenis syndrome, 882 Klippel–Trenaunay syndrome, Proteus velo‐cardio‐facial syndrome, 304 Juberg–Marsidi syndrome, differential diagnosis, syndrome, 766 Intrauterine movement, arthrogryposis and ATR‐X syndrome, 102 KMT2A gene mutations, Cornelia de Lange decrease in, 76 Juvenile myelomonocytic leukemia: syndrome, 212 Inverted duplicated chromosome 15 syndrome, neurofibromatosis type 1, 640 KMT2D gene mutations, Kabuki syndrome, 515–528 Noonan syndrome, 660 530, 531 dermatologic anomalies, 524–525 Juvenile polyposis: Knee instability, achondroplasia, 23–24 development and behavior problems, 519–522 differential diagnosis, PTEN hamartoma tumor KRAS mutations: diagnostic criteria, 515–516 syndrome, 781 cardio‐facio‐cutaneous syndrome, 148 diagnostic testing, 518 hereditary hemorrhagic telangiectasia, Noonan syndrome, 653 differential diagnosis, 518–519 476, 483 Kyphoscoliosis: endocrine anomalies, 524 Bardet–Biedl syndrome, 115. See also scoliosis etiology, pathogenesis, and genetics, 516–517 Kabuki syndrome, 529–538 Coffin–Lowry syndrome, 172, 179, 180, 181 growth and feeding problems, 519 cardiovascular anomalies, 533–534 Cohen syndrome, 203 incidence, 515 craniofacial anomalies, 535 Costello syndrome, 234 major malformations, 523–524 dental anomalies, 535 Ehlers–Danlos syndromes, 398 manifestations and management, 519–525 development and behavior problems, 532–533 Gorlin syndrome, 470 musculoskeletal anomalies, 524 diagnostic criteria, 529–530 Sotos syndrome, 910 neurological anomalies, 522–523 diagnostic testing, 531 Kyphosis: ophthalmologic anomalies, 524 differential diagnosis, 531–532 achondroplasia, 22–23 psychiatric problems, 519–522 deletion 22q11.2 syndrome, 298 arthrogryposis, 85 respiratory anomalies, 524 Williams syndrome, 1024 ATR‐X syndrome, 102

0004944829.INDD 1055 9/25/2020 7:13:43 AM 1056 INDEX

Kyphosis: (cont’d) inverted duplicated chromosome 15 syndrome, Marfan syndrome, 585 Kabuki syndrome, 536 520, 522 etiology, pathogenesis, and genetics, 564–566 Marfan syndrome, 588 Phelan–McDermid syndrome, 326 genetic counseling, 574 Prader–Willi syndrome, 738 Lentigines: growth and feeding problems, 569 Rett syndrome, 802 albinism, 51 immunologic conditions, 573 Noonan syndrome, 663 incidence, 563 LAMB2 mutations, Pierson syndrome, 342 LEOPARD syndrome: manifestations and management, 569–574 Lamotrigine, fetal anticonvulsant syndrome, 433 differential diagnosis musculoskeletal anomalies, 569–570 Language difficulties: Aarskog syndrome, 4 neurological anomalies, 572 achondroplasia, 17 Noonan syndrome, 654 ophthalmologic anomalies, 572 Angelman syndrome, 67 LETM1 gene, Wolf–Hirschhorn syndrome, 268 pregnancy, 573–574 Costello syndrome, 232 Leukemia, Down syndrome, 381–382 respiratory anomalies, 572–573 deletion 22q11.2 syndrome, 300 Levetiracetam: Long bone bowing, neurofibromatosis type 1, Down syndrome, 363 fetal anticonvulsant syndrome, 434 643, 644 fragile X syndrome, 447 Smith–Magenis syndrome, 884 Lordosis, Phelan–McDermid syndrome, 329 holoprosencephaly, 496 Lhermitte–Duclos disease, Cowden syndrome, Losartan, Marfan syndrome, 589 inverted duplicated chromosome 15 syndrome, 785–786 LOXL3 gene mutations, Stickler syndrome, 918 520 “Lick and flip” behavior, Smith–Magenis Lujan–Fryns syndrome, differential diagnosis, Kabuki syndrome, 532 syndrome, 867 Marfan syndrome, 586 Klinefelter syndrome, 544 Li–Fraumeni syndrome, Wilms tumor, 343 Lumbosacral spinal stenosis, achondroplasia, 23 Mowat–Wilson syndrome, 602 Limb anomalies. See also Hand anomalies Lung transplantation, tuberous sclerosis myotonic dystrophy type 1, 618 cardio‐facio‐cutaneous syndrome, 152 complex, 972 Noonan syndrome, 657 CHARGE syndrome, 159 Luteinizing hormone, Klinefelter syndrome, 548 Phelan–McDermid syndrome, 323 Coffin–Siris syndrome, 190 Lymphangioleiomyomatosis, tuberous sclerosis Prader–Willi syndrome, 736, 744 Cornelia de Lange syndrome, 216–217 complex, 959, 971, 972 Smith–Magenis syndrome, 873 craniosynostosis syndromes, 241 Lymphatic disorders: Sotos syndrome, 905 deletion 1p36 syndrome, 259 Noonan syndrome, 661–662 Turner syndrome, 986 fetal anticonvulsant syndrome, 437 Turner syndrome, 983–984 Large for gestational age: Grieg cephalopolysyndactyly syndrome, 714 Lymphedema: Beckwith‐Wiedemann syndrome, 134 Pallister–Hall syndrome, 712–713 Noonan syndrome, 661 fetal anticonvulsant syndrome, 434 Pallister–Killian syndrome, 718 Phelan–McDermid syndrome, 328, 329 Sotos syndrome, 901 Rett syndrome, 802 Sotos syndrome, 909 Larsen syndrome, differential diagnosis, Kabuki Silver–Russell syndrome, 845–846 Turner syndrome, 980, 983, 984 syndrome, 531 trisomy 13 and 18 syndromes, 951 Lymphoreticular malignancy, Sotos Laryngomalacia: VATER/VACTERL association, 999, 1000 syndrome, 910 CHARGE syndrome, 164 Wolf–Hirschhorn syndrome, 274 Coffin–Siris syndrome, 190 WT1‐related disorders, 345 Mabry syndrome, differential diagnosis, Laser photocoagulation: Lim kinase 1 (LIMK1) gene mutation, Williams Coffin–Siris syndrome, 187 hereditary hemorrhagic telangiectasia, 478 syndrome, 1023 McCune–Albright syndrome, differential Stickler syndrome, 921 Lipodermoids, oculo‐auriculo‐vertebral diagnosis, neurofibromatosis type 1, von Hippel–Lindau syndrome, 1013 spectrum, 677 634, 635 Laughter, spontaneous, Angelman syndrome, Lithium: McKusick–Kaufman syndrome, differential 61, 67 Phelan–McDermid syndrome, 325 diagnosis: Laurence–Moon syndrome. See Bardet–Biedl Smith–Magenis syndrome, 877 Bardet–Biedl syndrome, 112 syndrome Little People of America, Medical Advisory Pallister–Hall syndrome, 710 Learning disabilities. See also Cognitive function; Board, achondroplasia, 12 Macrocephaly: Intellectual disabilities; Mental retardation Liver disease: achondroplasia, 17 achondroplasia, 17 Alagille syndrome, 31 Bardet–Biedl syndrome, 108 Bardet–Biedl syndrome, 113 hereditary hemorrhagic telangiectasia, 482 Costello syndrome, 228 CHARGE syndrome, 161 Smith–Lemli–Opitz syndrome, 855 Gorlin syndrome, 464 Cohen syndrome, 197 Turner syndrome, 988–989 Greig cephalopolysyndactyly syndrome, 707 deletion 22q11.2 syndrome, 301 Liver transplants, Alagille syndrome, inverted duplicated chromosome 15 syndrome, Down syndrome, 373 37, 38 523 holoprosencephaly, 495–496 Lobar holoprosencephaly, 487 PTEN hamartoma tumor syndrome, 780, 786 Klinefelter syndrome, 544 diagnostic criteria, 488 tuberous sclerosis complex, 964 myotonic dystrophy type 1, 618 incidence, 488 Macroglossia, Beckwith–Wiedemann syndrome, neurofibromatosis type 1, 637 Loeys–Dietz syndrome, 563–576 134, 136 Noonan syndrome, 656 cardiovascular anomalies, 570–572 Macroorchidism, fragile X syndrome, 452 Sotos syndrome, 906 craniofacial anomalies, 570 Maculopathy, Bardet–Biedl syndrome, 114 tuberous sclerosis complex, 964 dermatologic anomalies, 573 Maffucci syndrome, differential diagnosis, Turner syndrome, 986 development and behavior problems, 569 hemihyperplasia, 766 Legius syndrome, differential diagnosis, diagnostic criteria, 563–564 Male pseudohermaphrodites, ATR‐X neurofibromatosis type 1, 634–635 diagnostic testing, 566–567 syndrome, 101 Leg ulceration, Klinefelter syndrome, 552 differential diagnosis, 567–568 Male X chromosome aneuploidy, 552–559 Lennox–Gestaut syndrome: Ehlers–Danlos syndromes, 398 46,XY/47,XXY mosaicism, 552

0004944829.INDD 1056 9/25/2020 7:13:43 AM INDEX 1057

48,XXXY syndrome, 553–556 Melatonin: Smith–Lemli–Opitz syndrome, 857 48,XXYY syndrome, 552–553 inverted duplicated chromosome 15 syndrome, Microhamartomatous rectal polyps, tuberous 49,XXXXY syndrome, 556–559 522 sclerosis complex, 972 Malignancy. See Neoplasia Rett syndrome, 799 Microphthalmia, CHARGE syndrome, 163 Malignant hyperthermia: Smith–Magenis syndrome, 879–880 Microstomia, Cornelia de Lange syndrome, 216 arthrogryposis, 87 tuberous sclerosis complex, 965 Miller syndrome, differential diagnosis: Noonan syndrome, 659 Williams syndrome, 1026, 1028 Robin sequence, 809 Malignant peripheral nerve sheath tumors, Meningiomas, Proteus syndrome, 771 Treacher Collins syndrome, 930 neurofibromatosis type 1, 638–639 Menopause, premature, fragile X syndrome, 453 Milroy disease, differential diagnosis, Turner Mandibulofacial dysostoses syndromes, 809, 929 Mental retardation. See also Cognitive function; syndrome, 980 Marfan syndrome, 577–596 Intellectual disabilities; Learning Minocycline, fragile X syndrome, 445, 446 cardiovascular anomalies, 588–590 disabilities Mitochondrial myopathy, Prader–Willi dermatologic anomalies, 592 Alagille syndrome, 32, 36 syndrome, 749 development and behavior problems, 587 ATR‐X syndrome, 93–105 Mitral valve prolapse: diagnostic criteria, 577–580 Bardet–Biedl syndrome, 108 fragile X syndrome, 451 diagnostic testing, 582–583 Coffin–Lowry syndrome, 174 Sotos syndrome, 909 differential diagnosis, 583–586 Cohen syndrome, 200 Stickler syndrome, 916, 923 Ehlers–Danlos syndromes, 398 trisomy 13 and 18 syndromes, 943 Modafinil: Loeys–Dietz syndrome, 567 WAGR syndrome, 344 myotonic dystrophy type 1, 618, 619 Sotos syndrome, 901 Metabolic disorders, differential diagnosis, Smith–Magenis syndrome, 879 etiology, pathogenesis, and genetics, 580–582 Alagille syndrome, 35 Mosaic genome‐wide paternal uniparental growth and feeding problems, 586–587 Metastatic disease, von Hippel–Lindau isodisomy, differential diagnosis, incidence, 577 syndrome, 1013 Beckwith–Wiedemann syndrome, 133 manifestations and management, 586–593 Metatarsus adduction, Aarskog syndrome, 6 Mosaicism: musculoskeletal anomalies, 587–588 Metformin, fragile X syndrome, 446 Alagille syndrome, 34 neonatal, 583–584 Methionine amino peptidase 2 (METAP2) Down syndrome, 358 neurological anomalies, 591 inhibitor, Prader–Willi syndrome, 747 46,XY/47,XXY, 552 ophthalmologic anomalies, 590–591 Methotrexate, Robin sequence, 811 WT1‐related disorders, 341 pregnancy management, 592–593 Methylation‐specific multiplex ligation‐ Mosaic overgrowth disorders, Proteus syndrome, respiratory anomalies, 591–592 dependent probe amplification (MS‐ 763–773 Marshall syndrome, differential diagnosis, MLPA), Prader–Willi syndrome, 740–741 Mosaic trisomy 12p, Pallister–Killian syndrome, Stickler syndrome, 919 Methylation‐specific polymerase chain reaction, 722, 724 Maternal age: Beckwith–Wiedemann syndrome, 132 Motor development problems: Down syndrome, 355, 358, 359, 360 Methylene tetrahydrofolate reductase gene achondroplasia, 17, 24 inverted duplicated chromosome 15 syndrome, (MTHFR) polymorphisms, trisomy 18 Coffin–Lowry syndrome, 181 516, 517 syndrome, 939 48,XXXY syndrome, 554 Klinefelter syndrome, 541 Metopic synostosis, differential diagnosis, Phelan–McDermid syndrome, 323–324 Pallister–Killian syndrome, 720, 722 craniosynostosis syndromes, 246 Sotos syndrome, 905 Prader–Willi syndrome, 740 Microcephaly. See also Craniofacial anomalies Williams syndrome, 1026 trisomy 18 syndrome, 939, 940 Angelman syndrome, 69 Mowat–Wilson syndrome, 597–609 Meacham syndrome, 335 ATR‐X syndrome, 100 cardiovascular anomalies, 604 cardiovascular anomalies, 346 Coffin–Lowry syndrome, 172 development and behavior problems, 602–603 diagnostic criteria, 337, 338 Cohen syndrome, 202 diagnostic criteria, 598 diagnostic testing, 341–342 holoprosencephaly, 498 diagnostic testing, 599–600 differential diagnosis, 342–343 Mowat–Wilson syndrome, 601 differential diagnosis, 601 etiology, pathogenesis, and genetics, 339–341 Silver–Russell syndrome, 842 Angelman syndrome, 66 genitourinary anomalies, 346–347 Smith–Lemli–Opitz syndrome, 857 ear anomalies, 605 incidence, 335 Wolf–Hirschhorn syndrome, 266 endocrine anomalies, 605 pulmonary anomalies, 346 Microdeletion: etiology, pathogenesis, and genetics, 598 Meckel–Gruber syndrome, differential diagnosis, Angelman syndrome, 64 gastrointestinal anomalies, 603 trisomy 13 syndrome, 943 Beckwith–Wiedemann syndrome, 132 genetic counseling, 600–601 Meckel’s diverticulum, trisomy 18 syndrome, 951 Coffin–Siris syndrome, 187 genitourinary anomalies, 604–605 Meckel syndrome, differential diagnosis, craniosynostosis syndromes, 246 growth and feeding problems, 601–602 Smith–Lemli–Opitz syndrome, 854 deletion 22q11.2 syndrome, 291 hearing disorders, 605 MECP2 gene mutation, Rett syndrome, 791, 795, holoprosencephaly, 492 immunologic conditions, 605–606 796 neurofibromatosis type 1, 637 incidence, 597–598 Medroxy‐progesterone, tuberous sclerosis Prader–Willi syndrome, 735 manifestations and management, 601–606 complex, 972 Robin sequence, 810 musculoskeletal anomalies, 605 Medulloblastoma, Gorlin syndrome, 468 Rubinstein–Taybi syndrome, 825 neurological anomalies, 603–604 Meige disease, differential diagnosis, Turner Wolf–Hirschhorn syndrome, 269 ophthalmologic anomalies, 605 syndrome, 980 Micrognathia: Moyamoya disease, and Smith–Magenis MEK1/ MED2 mutations: CHARGE syndrome, 164 syndrome, 882 cardio‐facio‐cutaneous syndrome, 148, 149 Cornelia de Lange syndrome, 212, 216 MSX1 gene, Wolf–Hirschhorn syndrome, 269 Costello syndrome, 227 Robin sequence, 808, 810, 814, 817–818 MTOR inhibitors, tuberous sclerosis complex, Melanin anomalies, albinism, 45, 47 Silver–Russell syndrome, 845 967, 972

0004944829.INDD 1057 9/25/2020 7:13:43 AM 1058 INDEX

Mucocutaneous lesions, PTEN hamartoma tumor Prader–Willi syndrome, 754–755 hearing disorders, 622 syndrome, 785 Proteus syndrome, 767–768 incidence, 611 Mucopolysaccharidosis MPSIII (Sanfillippo Rett syndrome, 802 manifestations and management, 616–624 syndrome), differential diagnosis, Sotos Rubinstein–Taybi syndrome, 831–832 musculoskeletal anomalies, 622–623 syndrome, 901 Silver–Russell syndrome, 845–846 neurological anomalies, 618–619 Muenke syndrome: Smith–Lemli–Opitz syndrome, 860 neuromuscular weakness, 618 development and behavior problems, 247 Smith–Magenis syndrome, 885 ophthalmologic anomalies, 622 diagnostic criteria, 243 Sotos syndrome, 910–911 pregnancy and delivery, 623–624 diagnostic testing, 246 Stickler syndrome, 922–923 respiratory anomalies, 620–621 etiology, pathogenesis, and genetics, 245 trisomy 13 and 18 syndromes, 951–952 Myotonic dystrophy type 2, differential growth and feeding problems, 246–247 VATER/VACTERL association, 999–1000 diagnosis, myotonic dystrophy hearing disorders, 248 Williams syndrome, 1033 type 1, 616 Multifocal micronodular pneumocyte Wolf–Hirschhorn syndrome, 274–275 Myringotomy: hyperplasia, tuberous sclerosis WT1‐related disorders, 345 achondroplasia, 21 complex, 971 Music: oculo‐auriculo‐vertebral spectrum, 677 Multi‐locus imprinting disorder, Beckwith– cardio‐facio‐cutaneous syndrome, 150 Wiedemann syndrome, 131 fragile X syndrome, 448, 452 Nager syndrome: Multiple lentingines syndrome, differential inverted duplicated chromosome 15 syndrome, differential diagnosis, Treacher Collins diagnosis, neurofibromatosis 521 syndrome, 929–930 type 1, 635 Mowat–Wilson syndrome, 602 Robin sequence, 809 Multiplex ligation‐dependent probe amplification Phelan–McDermid syndrome, 324, 325 Nail dystrophy, incontinentia pigmenti, 510 (MLPA), WAGR syndrome, 321, 342 Rett syndrome, 800 Nail‐patella syndrome, differential diagnosis, Muscular dystrophy, myotonic dystrophy Williams syndrome, 1028 WT1‐related disorders, 342 type 1, 611 Myeloproliferative disorder, Noonan Neonatal hypotonia. See Hypotonia Musculoskeletal anomalies: syndrome, 660 Neoplasia: Aarskog syndrome, 6 MYO15A gene mutation, Smith–Magenis ATR‐X syndrome, 103 achondroplasia, 9, 22–26 syndrome, 870 Bannayan–Riley–Ruvalcaba syndrome, 777 Alagille syndrome, 33, 40–41 Myopathy: Beckwith–Wiedemann syndrome, 137–139 Angelman syndrome, 70 deletion 1p36 syndrome, 259 cardio‐facio‐cutaneous syndrome, 153 arthrogryposis, 85–87 differential diagnosis Coffin–Lowry syndrome, 181–182 ATR‐X syndrome, 102 Angelman syndrome, 65 Coffin–Siris syndrome, 191–192 Bardet–Biedl syndrome, 115 Costello syndrome, 230, 234 Costello syndrome, 227–228, 235–236 cardio‐facio‐cutaneous syndrome, 152–153 Noonan syndrome, 659 deletion 1p36 syndrome, 261 Coffin–Lowry syndrome, 181 Myopia: Down syndrome, 381–383 Coffin–Siris syndrome, 190 ATR‐X syndrome, 103 fetal anticonvulsant syndrome, 438 Cohen syndrome, 203–204 cardio‐facio‐cutaneous syndrome, 152 Gorlin syndrome, 468–469 Cornelia de Lange syndrome, 216–217 Cohen syndrome, 201 Klinefelter syndrome, 551 Costello syndrome, 233–234 Cornelia de Lange syndrome, 218 neurofibromatosis type 1, 638–642 craniosynostosis syndromes, 249 Loeys–Dietz syndrome, 572 Noonan syndrome, 659–661 deletion 1p36 syndrome, 259–260 Marfan syndrome, 590, 591 Pallister–Killian syndrome, 730 deletion 5p syndrome, 286 Phelan–McDermid syndrome, 327 Proteus syndrome, 771–772 deletion 22q11.2 syndrome, 307–308 Prader–Willi syndrome, 738 PTEN hamartoma tumor syndrome, 782–783 Down syndrome, 373–375 Smith–Magenis syndrome, 885 Rubinstein–Taybi syndrome, 832 fetal alcohol spectrum disorders, 417 Stickler syndrome, 920–921 Sotos syndrome, 910 fetal anticonvulsant syndrome, 437–438 Turner syndrome, 989 trisomy 13 and 18 syndromes, 950 49,XXXXY syndrome, 557 Myotonic dystrophy type 1, 611–627 Turner syndrome, 981, 990 fragile X syndrome, 452–453 anesthesia risks, 624 von Hippel–Lindau syndrome, 1009, Gorlin syndrome, 470 cardiovascular anomalies, 621–622 1010–1014 Greig cephalopolysyndactyly syndrome, 714 dental anomalies, 619 Wolf–Hirschhorn syndrome, 275–276 incontinentia pigmenti, 512 dermatologic anomalies, 622 WT1‐related disorders, 341 inverted duplicated chromosome 15 syndrome, development and behavior problems, 618 Nephropathy, WT1‐related disorders, 347–348 524 diagnostic criteria, 611–615 Nephrotic syndrome, differential diagnosis, Kabuki syndrome, 536 adult onset, 614–615 WT1‐related disorders, 342–343 Klinefelter syndrome, 550–551 childhood, 613 Netchine–Harbison clinical scoring system, Loeys–Dietz syndrome, 569–570 congenital, 612–613 Silver–Russell syndrome, 838 Marfan syndrome, 587–588 late‐onset, 615 Neuroblastoma: Mowat–Wilson syndrome, 605 subtypes, 611–612 Beckwith–Wiedemann syndrome, 137 myotonic dystrophy type 1, 622–623 diagnostic testing, 615, 617 Costello syndrome, 235–236 neurofibromatosis type 1, 642–644 differential diagnosis, 615–616 deletion 1p36 syndrome, 261 Noonan syndrome, 662–663 ear anomalies, 622 fetal anticonvulsant syndrome, 438 oculo‐auriculo‐vertebral spectrum, 678 endocrine anomalies, 623 Sotos syndrome, 910 osteogenesis imperfecta, 695–698 etiology, pathogenesis, and genetics, 615 Turner syndrome, 990 Pallister–Hall syndrome, 712–713 gastrointestinal anomalies, 619–620 Neurofibromatosis type 1, 629–649 Pallister–Killian syndrome, 728–729 genetic counseling, 616–617 cardiovascular anomalies, 645 Phelan–McDermid syndrome, 328–329 growth and feeding problems, 617 development and behavior problems, 637–638

0004944829.INDD 1058 9/25/2020 7:13:43 AM INDEX 1059

diagnostic criteria, 629–632 Williams syndrome, 1028–1029 albinism, 48, 50, 52 diagnostic testing, 634 Wolf–Hirschhorn syndrome, 271–272 Bardet–Biedl syndrome, 114 differential diagnosis, 634–635 WT1‐related disorders, 344–345 cardio‐facio‐cutaneous syndrome, 152 etiology, pathogenesis, and genetics, 632–634 Neutropenia, Cohen syndrome, 202, 203 CHARGE syndrome, 163 genetic counseling, 633–634 Nevi: oculocutaneous albinism, 47 growth and feeding problems, 636–637 Gorlin syndrome, 465–466 incidence, 629 Turner syndrome, 990 OA1 gene. See GPR143 gene mutations manifestations and management, 635–645 Nevoid basal cell carcinoma syndrome. See Obesity: musculoskeletal anomalies, 642–644 Gorlin syndrome achondroplasia, 12 neoplasia incidence, 638–642 Nevus anemicus, differential diagnosis, tuberous Angelman syndrome, 66 Neurofibromatosis type 2: sclerosis complex, 963 arthrogryposis, 84 differential diagnosis, neurofibromatosis type Next generation sequencing: Bardet–Biedl syndrome, 112 1, 635 Mowat–Wilson syndrome, 599 Coffin–Lowry syndrome, 175 Phelan–McDermid syndrome, 320 WT1‐related disorders, 342 Down syndrome, 362 Neurofibromin, neurofibromatosis type 1, NF1 gene mutations, neurofibromatosis 48,XXXY syndrome, 556 632, 633 type 1, 630 osteogenesis imperfecta, 694 Neurological anomalies: Nicolaides–Baraitser syndrome, differential Prader–Willi syndrome, 735, 736–737, Aarskog syndrome, 6 diagnosis: 746–749 achondroplasia, 17–20 Coffin–Siris syndrome, 187 Smith–Magenis syndrome, 871–872 Angelman syndrome, 69 Cornelia de Lange syndrome, 212, 213 Turner syndrome, 987 arthrogryposis, 87 NIPBL gene mutation, Cornelia de Lange WAGR syndrome, 344 ATR‐X syndrome, 100–101 syndrome, 210–211, 215 Obsessive‐compulsive disorder: Bardet–Biedl syndrome, 118 Nociception, impairment, Rett syndrome, CHARGE syndrome, 162 cardio‐facio‐cutaneous syndrome, 151 800–801 Cornelia de Lange syndrome, 214 Coffin–Lowry syndrome, 178–179 Noonan syndrome, 651–669 deletion 5p syndrome, 284 Coffin–Siris syndrome, 188–190 cardiovascular anomalies, 657–658 Down syndrome, 364 Cohen syndrome, 202 dermatologic anomalies, 663 fragile X syndrome, 447, 449 Cornelia de Lange syndrome, 219 development and behavior problems, 656–657 Prader–Willi syndrome, 744 Costello syndrome, 234–235 diagnostic criteria, 651–653 Smith–Magenis syndrome, 875 craniosynostosis syndromes, 249 diagnostic testing, 654 Turner syndrome, 986 deletion 1p36 syndrome, 257–258 differential diagnosis, 654–655 WAGR syndrome, 344 deletion 5p syndrome, 285 Aarskog syndrome, 4 Obstructive cardiomyopathy: deletion 22q11.2 syndrome, 304–305 cardio‐facio‐cutaneous syndrome, 149 cardio‐facio‐cutaneous syndrome, 151 Down syndrome, 380–381 Costello syndrome, 230 Noonan syndrome, 658 fetal alcohol spectrum disorders, 417–418, 436 fetal anticonvulsant syndrome, 428 Obstructive sleep apnea, 179 49,XXXXY syndrome, 556–557 neurofibromatosis type 1, 635 achondroplasia, 20, 21 fragile X syndrome, 449–450 Smith–Lemli–Opitz syndrome, 854 deletion 22q11.2 syndrome, 302 Greig cephalopolysyndactyly syndrome, Turner syndrome, 980 Down syndrome, 376 713–714 Williams syndrome, 1024 myotonic dystrophy type 1, 620 hereditary hemorrhagic telangiectasia, ear anomalies, 663–664 oculo‐auriculo‐vertebral spectrum, 679 481–482 etiology, pathogenesis, and genetics, 653–654 Prader–Willi syndrome, 746, 754 holoprosencephaly, 498–500 genetic counseling, 654 Robin sequence, 816–817 incontinentia pigmenti, 511–512 genitourinary anomalies, 662 Rubinstein–Taybi syndrome, 829, 830 inverted duplicated chromosome 15 syndrome, growth and feeding problems, 655–656 Treacher Collins syndrome, 931, 932 522–523 hearing disorders, 663–664 trisomy 13 and 18 syndromes, 952 Kabuki syndrome, 533 hematologic anomalies, 659–661 OCA2 gene mutations, Angelman syndrome, 49, Loeys–Dietz syndrome, 572 immunologic conditions, 664 64 Marfan syndrome, 591 incidence, 651 Occipitoatlantoaxial instability, Down syndrome, Mowat–Wilson syndrome, 603–604 lymphatic anomalies, 661–662 373–374 myotonic dystrophy type 1, 618 manifestations and management, 655–664 Ocular albinism, 45 Noonan syndrome, 658–659 musculoskeletal anomalies, 662–663 diagnostic criteria, 46 oculo‐auriculo‐vertebral spectrum, 677–678 neoplasia incidence, 659–661 differential diagnosis, 50 osteogenesis imperfecta, 698 neurological anomalies, 658–659 incidence, 46 Pallister–Hall syndrome, 711 ophthalmologic anomalies, 659 prenatal diagnosis, 49 Pallister–Killian syndrome, 726–727 Nose, Greek warrior helmet appearance, Oculo‐auriculo‐vertebral spectrum, 671–681 Phelan–McDermid syndrome, 325–327 Wolf–Hirschhorn syndrome, 266 cardiovascular anomalies, 678 Prader–Willi syndrome, 749–750 Nose bleeds, Prader–Willi syndrome, 755 craniofacial anomalies, 675–676 Proteus syndrome, 769 NOTCH2 mutations, Alagille syndrome, 31, 35 development and behavior problems, PTEN hamartoma tumor syndrome, 785–786 NSD1 gene mutation, Sotos syndrome, 895, 898, 674–675 Rett syndrome, 800–801 899, 910 diagnostic criteria, 671–672 Smith–Lemli–Opitz syndrome, 857 NSD2 gene mutation, Wolf–Hirschhorn diagnostic testing, 673 Smith–Magenis syndrome, 882–884 syndrome, 267–268 differential diagnosis, 673–674 Sotos syndrome, 907 Nyctalopia (night blindness). See Vision deletion 5p syndrome, 283 trisomy 13 and 18 syndromes, 947–948 impairment deletion 22q11.2 syndrome, 298 tuberous sclerosis complex, 965–968 Nystagmus: Treacher Collins syndrome, 930

0004944829.INDD 1059 9/25/2020 7:13:43 AM 1060 INDEX

Oculo‐auriculo‐vertebral spectrum (cont’d) myotonic dystrophy type 1, 622 cardio‐facio‐cutaneous syndrome, 152 ear anomalies, 676–677 Noonan syndrome, 659 osteogenesis imperfecta, 684 etiology, pathogenesis, and genetics, 672–673 oculo‐auriculo‐vertebral spectrum, 677 Prader–Willi syndrome, 755 genetic counseling, 673 osteogenesis imperfecta, 700–701 Osteoporosis: genitourinary anomalies, 678 Pallister–Hall syndrome, 713 arthrogryposis, 86 growth and feeding problems, 674 Pallister–Killian syndrome, 729 differential diagnosis, osteogenesis hearing disorders, 676–677 Phelan–McDermid syndrome, 327–328 imperfecta, 694 incidence, 671 Prader–Willi syndrome, 752 Klinefelter syndrome, 549 manifestations and management, 674–679 Proteus syndrome, 770 Prader–Willi syndrome, 755 musculoskeletal anomalies, 678 Rett syndrome, 803–804 Turner syndrome, 988 neurological anomalies, 677–678 Rubinstein–Taybi syndrome, 829 Osteotomy, Proteus syndrome, 767 ophthalmologic anomalies, 677 Smith–Lemli–Opitz syndrome, 858 Otitis media: respiratory anomalies, 678–679 Smith–Magenis syndrome, 884–885 arthrogryposis, 88 Robin sequence, 811 Sotos syndrome, 908 CHARGE syndrome, 165 severity classification, 672 Stickler syndrome, 920–921 Down syndrome, 372 Oculocutaneous albinism, 45 Treacher Collins syndrome, 932 fragile X syndrome, 451 dermatologic anomalies, 50–51 trisomy 13 and 18 syndromes, 949 Kabuki syndrome, 534–535 development and behavior problems, 50 tuberous sclerosis complex, 969 Mowat–Wilson syndrome, 605 diagnostic criteria, 46–47 Turner syndrome, 989 Noonan syndrome, 663, 664 diagnostic testing, 49 WAGR syndrome, 345 osteogenesis imperfecta, 699 differential diagnosis, 50 Williams syndrome, 1031–1032 Smith–Magenis syndrome, 867, 881, 887 etiology, pathogenesis, and genetics, 47 Wolf–Hirschhorn syndrome, 274 Sotos syndrome, 908 incidence, 45 WT1‐related disorders, 345–346 Stickler syndrome, 921, 922 types of, 45–46 Opitz G/BBB syndrome, deletion 22q11.2 Turner syndrome, 989 Okihiro syndrome, differential diagnosis, oculo‐ syndrome, 291, 304 Williams syndrome, 1032 auriculo‐vertebral spectrum, 673–674 Opitz G syndrome, differential diagnosis, Otolaryngologic anomalies. See also Ears, Olfaction, Bardet–Biedl syndrome, 118 Mowat–Wilson syndrome, 601 anomalies of Oliver–McFarlane syndrome, differential Optic nerve atrophy, cardio‐facio‐cutaneous craniosynostosis syndromes, 248 diagnosis, Bardet–Biedl syndrome, 107 syndrome, 152 hereditary hemorrhagic telangiectasia, Oncologic conditions. See Neoplasia Oral‐facial‐digital syndromes, differential 478–479 Onychotillomania (nail yanking), Smith–Magenis diagnosis, Pallister–Hall syndrome, 710 Pallister–Hall syndrome, 712 syndrome, 867, 874 Oral insertion behavior, Smith–Magenis Proteus syndrome, 770 Ophthalmologic anomalies: syndrome, 874 Smith–Magenis syndrome, 881–882 Aarskog syndrome, 5 Oral sensorimotor dysfunction, Smith–Magenis Sotos syndrome, 907–908 Alagille syndrome, 40 syndrome, 872, 881 Otorhinolaryngologic anomalies, hereditary albinism, 46, 52–53 Osler–Weber–Rendu disease. See Hereditary hemorrhagic telangiectasia, 478–479 Angelman syndrome, 70 hemorrhagic telangiectasia Ovarian cystadenomas, Proteus syndrome, 770 arthrogryposis, 87 Osteoarthritis, Stickler syndrome, 922 Ovarian fibromas, Gorlin syndrome, 470 ATR‐X syndrome, 103 Osteochondrodystrophies. See Musculoskeletal Overfriendliness, Williams syndrome, 1026 Bardet–Biedl syndrome, 114 anomalies Overgrowth disorders: cardio‐facio‐cutaneous syndrome, 152 Osteogenesis imperfecta, 683–705 Beckwith–Wiedemann syndrome, 125, 840 CHARGE syndrome, 162–163 adult health, 701 Proteus syndrome, 763 Coffin–Lowry syndrome, 179 cardiovascular anomalies, 700 Smith–Magenis syndrome, 871 Cohen syndrome, 201–202 classification, 683 Sotos syndrome, 896, 897 Cornelia de Lange syndrome, 218 dental anomalies, 699 Oxcarbazepine, fetal anticonvulsant Costello syndrome, 235 development and behavior problems, 695 syndrome, 434 craniosynostosis syndromes, 248–249 diagnostic criteria, 684–691 Oxytocin, Prader–Willi syndrome, 742 deletion 1p36 syndrome, 259 diagnostic testing, 693 deletion 5p syndrome, 286 differential diagnosis, 693–694 Pain perception and management: deletion 22q11.2 syndrome, 306–307 hypermobile Ehlers‐Danlos syndrome, 396 Noonan syndrome, 663 Down syndrome, 372–373 Silver–Russell syndrome, 843 osteogenesis imperfecta, 698 fetal alcohol spectrum disorders, 415–416 ear anomalies, 698–699 Prader–Willi syndrome, 749–750 fetal anticonvulsant syndrome, 437 etiology, pathogenesis, and genetics, 691–693 Smith–Magenis syndrome, 883 fragile X syndrome, 450 genetic counseling, 684, 692–693 Palivizumab, Down syndrome, 379 Gorlin syndrome, 469 growth and feeding problems, 694–695 Pallister–Hall syndrome, 707–716 hereditary hemorrhagic telangiectasia, hearing disorders, 698–699 dental anomalies, 713 483–484 incidence and prevalence, 684 development and behavior problems, 710 holoprosencephaly, 500 manifestations and management, 694–701 diagnostic criteria, 707–708 incontinentia pigmenti, 510–511 musculoskeletal anomalies, 695–698 diagnostic testing, 709–710 inverted duplicated chromosome 15 syndrome, neurological anomalies, 698 differential diagnosis, 710 524 ophthalmologic anomalies, 700–701 Smith–Lemli–Opitz syndrome, 854 Kabuki syndrome, 534 pulmonary anomalies, 699–700 endocrine anomalies, 711–712 Loeys–Dietz syndrome, 572 renal anomalies, 701 etiology, pathogenesis, and genetics, 708–709 Marfan syndrome, 590–591 Osteopenia: gastrointestinal anomalies, 712 Mowat–Wilson syndrome, 605 arthrogryposis, 86 genitourinary anomalies, 712

0004944829.INDD 1060 9/25/2020 7:13:43 AM INDEX 1061

growth and feeding problems, 710 Peripheral neurofibromatosis. See PIGG gene, Wolf–Hirschhorn syndrome, 268 incidence, 707 Neurofibromatosis type 1 Pigmentary mosaicism, differential diagnosis, manifestations and management, 710–713 Peripheral neuropathy, Smith–Magenis incontinentia pigmenti, 508 musculoskeletal anomalies, 712–713 syndrome, 882–883 Pigmentation anomalies: neurological anomalies, 711 Peripheral pulmonic stenosis, Williams albinism, 45 ophthalmologic anomalies, 713 syndrome, 1030 Cohen syndrome, 197 otolaryngologic anomalies, 712 Perlman syndrome: Pallister–Killian syndrome, 717 respiratory anomalies, 713 differential diagnosis, Beckwith–Wiedemann PIK3CA‐related overgrowth spectrum (PROS), Pallister–Killian syndrome, 717–733 syndrome, 133 differential diagnosis, Proteus syndrome, cardiovascular anomalies, 727–728 Wilms tumor, 343 763, 765–766 dental anomalies, 730 Peutz–Jeghers syndrome, differential diagnosis, Pilomatrixomata, myotonic dystrophy type 1, 622 dermatologic anomalies, 728 PTEN hamartoma tumor syndrome, 781 Pipamperon, Rett syndrome, 799 development and behavior problems, 725–726 Pfeiffer syndrome: Pitt–Hopkins syndrome, differential diagnosis: diagnostic criteria, 718–720 cardiovascular anomalies, 249 ATR‐X syndrome, 98 diagnostic testing, 721–722 development and behavior problems, 247 Mowat–Wilson syndrome, 601 differential diagnosis, 722–724 diagnostic criteria, 243 Rett syndrome, 797 ear anomalies, 729–730 diagnostic testing, 246 Pitt–Rogers–Danks syndrome, differential etiology, pathogenesis, and genetics, 720–721 etiology, pathogenesis, and genetics, 245 diagnosis, Wolf–Hirschhorn gastrointestinal anomalies, 727 genitourinary anomalies, 250 syndrome, 270 genetic counseling, 721 musculoskeletal anomalies, 249 Plexiform neurofibromas, neurofibromatosis genitourinary anomalies, 728 otolaryngologic anomalies, 248 type 1, 638, 642 growth and feeding problems, 724–725 P gene. See OCA2 gene mutations PLOD1 gene mutation, kyphoscoliotic Ehlers‐ hearing disorders, 729–730 Phelan–McDermid syndrome, 317–334 Danlos syndrome, 398 incidence, 717–718 cardiovascular anomalies, 328 PNPLA6 gene mutation, Bardet–Biedl manifestations and management, 724–730 dental anomalies, 328 syndrome, 107 musculoskeletal anomalies, 728–729 dermatologic anomalies, 329–330 Polydactyly: neurological anomalies, 726–727 development and behavior problems, 322–325 Bardet–Biedl syndrome, 110, 115 ophthalmologic anomalies, 729 diagnostic criteria, 317–318 Greig cephalopolysyndactyly syndrome, pulmonary anomalies, 730 diagnostic testing, 321 708, 714 Palmoplantar hyperkeratosis, cardio‐facio‐ differential diagnosis, 321 Pallister–Hall syndrome, 708, 713 cutaneous syndrome, 152 Rett syndrome, 797 Polyembolokoilamania, Smith–Magenis Pamidronate, osteogenesis imperfecta, 697 ear anomalies, 327 syndrome, 867 Pancreatic cystic lesions, von Hippel–Lindau etiology, pathogenesis, and genetics, 318–321 Polyhydramnios: syndrome, 1014, 1015 gastrointestinal anomalies, 329 arthrogryposis, 76 Pancreatic insufficiency, Alagille syndrome, 37 genitourinary anomalies, 330–331 Beckwith–Wiedemann syndrome, 139, 140 Panhypopituitarism, Pallister–Hall syndrome, 711 growth and feeding problems, 322 cardio‐facio‐cutaneous syndrome, 147, 149 Pansynostosis: hearing disorders, 327 CHARGE syndrome, 164 craniosynostosis syndromes, 246, 249 immunologic conditions, 330 Cornelia de Lange syndrome, 212 Crouzon syndrome, 242 incidence, 317 Costello syndrome, 228 Papillary cystadenomas, von Hippel–Lindau manifestations and management, 322–331 deletion 22q11.2 syndrome, 296 syndrome, 1015 musculoskeletal anomalies, 328–329 myotonic dystrophy type 1, 612 Papillomas, Costello syndrome, 236 neurological anomalies, 325–327 Noonan syndrome, 661 Parkinson disease, deletion 22q11.2 ophthalmologic anomalies, 327–328 Pallister–Killian syndrome, 724 syndrome, 304 respiratory anomalies, 330 Robin sequence, 811 Patau syndrome. See Trisomy 13 syndrome Phenobarbital embryopathy, fetal anticonvulsant trisomy 18 syndrome, 940 Patent ductus arteriosus: syndrome, 432 VATER/VACTERL association, 1000 CHARGE syndrome, 163 Phenytoin: velo‐cardio‐facial syndrome, 296 Rubinstein‐Taybi syndrome, 830 fetal anticonvulsant syndrome, 426, 427, 429, Polyvalvular disease, trisomy 13 and 18 Sotos syndrome, 908 432, 435 syndromes, 948 PAX6 gene mutation, WAGR syndrome, 336 Wolf–Hirschhorn syndrome, 272 Ponseti method, arthrogryposis, 86 Pectus excavatum: Pheochromocytoma: Porokeratosis of Mantoux, differential diagnosis, Aarskog syndrome, 6 neurofibromatosis type 1, 645 Gorlin syndrome, 463 Coffin–Lowry syndrome, 181 von Hippel–Lindau syndrome, 1006, 1007, Postaxial polydactyly: Pemphigus vulgaris, deletion 1p36 syndrome, 261 1008–1009, 1011, 1013–1014 Bardet‐Biedl syndrome, 115 PEMT gene mutation, Smith–Magenis syndrome, Phosphatidylethanolamine N‐methyltransferase, Hall‐Pallister syndrome, 707–709 870 Smith–Magenis syndrome, 870 Smith–Lemli–Opitz syndrome, 860 Pena–Shokeir phenotype: Photodynamic therapy, Gorlin syndrome, 467 trisomy 13 syndrome, 951 arthrogryposis, 76 Photophobia: Posterior embryotoxon, Alagille syndrome, differential diagnosis, trisomy 18 syndrome, Rubinstein–Taybi syndrome, 829 32–33, 35–36, 40 941 Smith–Lemli–Opitz syndrome, 860 Posterior laminectomy, achondroplasia, 23 Peptic ulcers, ATR‐X syndrome, 100 trisomy 18 syndrome, 949 Post‐traumatic stress disorder, Smith–Magenis Perinatal care, Beckwith–Wiedemann syndrome, Pidotimod, Down syndrome, 379 syndrome, 875 139–140 Pierre Robin sequence. See Robin sequence Prader–Willi syndrome, 735–761 Perioral blueness, Cornelia de Lange Pierson syndrome, differential diagnosis, anesthesia risks, 756 syndrome, 218 WT1‐related disorders, 342 Angelman syndrome and, 62

0004944829.INDD 1061 9/25/2020 7:13:43 AM 1062 INDEX

Prader–Willi syndrome (cont’d) cardiovascular anomalies, 771 Noonan syndrome, 659 and deletion 22q13 syndrome, 318 dental anomalies, 772 Phelan–McDermid syndrome, 327 dental anomalies, 754 dermatologic anomalies, 770–771 Rubinstein–Taybi syndrome, 829 dermatologic anomalies, 755–756 development and behavior problems, 767 Smith–Lemli–Opitz syndrome, 858 development and behavior problems, 744–746 diagnostic criteria, 763–764, 777 Turner syndrome, 989 diagnostic criteria, 736–739 diagnostic testing, 765 PTPN11 gene mutation, Noonan syndrome, diagnostic testing, 740–741 differential diagnosis, 765–766 4, 653 differential diagnosis, 741 etiology, pathogenesis, and genetics, 764–766 Puberty: Angelman syndrome, 65 gastrointestinal anomalies, 769 CHARGE syndrome, 166 Cohen syndrome, 199 genitourinary anomalies, 770 Cornelia de Lange syndrome, 218 deletion 1p36 syndrome, 255 growth and feeding problems, 766–767 Costello syndrome, 235 inverted duplicated chromosome 15 Happle model, 765 fragile X syndrome, 453 syndrome, 518 incidence, 763 inverted duplicated chromosome 15 syndrome, Klinefelter syndrome, 542 manifestations and management, 766–772 524 Smith–Magenis syndrome, 871 musculoskeletal anomalies, 767–768 neurofibromatosis type 1, 641 endocrine anomalies, 750–752 neoplasia incidence, 771–772 Noonan syndrome, 662 etiology, pathogenesis, and genetics, 739–740 neurological anomalies, 769 Pallister–Hall syndrome, 712 genetic counseling, 740 ophthalmologic anomalies, 770 Pallister–Killian syndrome, 730 growth and feeding problems, 742–744 otolaryngologic anomalies, 770 Prader–Willi syndrome, 750–751 hyperphagia, 112 PTEN hamartoma tumor syndrome, 775 Silver–Russell syndrome, 844–845 incidence, 735–736 respiratory anomalies, 768 Turner syndrome, 984–985 manifestations and management, 741–756 Proximal myotonic dystrophy. See Myotonic Pulmonary anomalies: musculoskeletal anomalies, 754–755 dystrophy type 2 albinism, 54 neuromuscular weakness, 749–750 Pruritus, Alagille syndrome, 36 Klinefelter syndrome, 552 ophthalmologic anomalies, 752 Pseudarthrosis, neurofibromatosis type 1, osteogenesis imperfecta, 699–700 respiratory anomalies, 753–754 643, 644 Pallister–Killian syndrome, 730 sleep abnormalities, 753 Pseudohypoparathyroidism, differential WT1‐related disorders, 346 Pregnancy: diagnosis, Gorlin syndrome, 463 Pulmonary arteriovenous malformation, achondroplasia, 26–27 Psoriasis, Down syndrome, 378 hereditary hemorrhagic telangiectasia, Beckwith–Wiedemann syndrome, 139–140 Psychiatric problems: 479–482 cardio‐facio‐cutaneous syndrome, 149 deletion 22q11.2 syndrome, 300–303 Pulmonary artery stenosis, Alagille syndrome, 32 fetal alcohol spectrum disorders, 418–419 Down syndrome, 366 Pulmonary bullous degeneration, Proteus Loeys–Dietz syndrome, 573–574 fragile X syndrome, 448, 449 syndrome, 768 Marfan syndrome, 592–593 inverted duplicated chromosome 15 syndrome, Pulmonary embolism, Proteus syndrome, 768 myotonic dystrophy type 1, 623–624 519–522 Pulmonary fibrosis, Hermansky–Pudlak osteogenesis imperfecta, 701 Prader–Willi syndrome, 745 syndrome, 48–49, 54 seizure disorders in, 438–439 Smith–Magenis syndrome, 877 Pulmonary hypertension: Turner syndrome and, 981, 982 Psychosocial issues: cardio‐facio‐cutaneous syndrome, 151 Pregnancy‐associated plasma protein‐A: Down syndrome, 362 Down syndrome, 369 Cornelia de Lange syndrome, 211–212 Loeys–Dietz syndrome, 569 incontinentia pigmenti, 512 Down syndrome, 360 Marfan syndrome, 587 Pallister–Killian syndrome, 728 Preimplantation genetic diagnosis, myotonic neurofibromatosis type 1, 632 trisomy 13 and 18 syndromes, 948, 952 dystrophy type 1, 617 oculo‐auriculo‐vertebral spectrum, 674 Pulmonary hypoplasia, arthrogryposis, 76 Premature thelarche, Kabuki syndrome, 534 Turner syndrome, 986 Pulmonary stenosis: Premutation‐associated disorders. See Fragile X velo‐cardio‐facial syndrome, 300 neurofibromatosis type 1, 645 syndrome von Hippel–Lindau syndrome, 1010 Noonan syndrome, 658 Prenatal diagnosis: PTCH gene mutations, Gorlin syndrome, Pulmonary veno‐occlusive disease, Down achondroplasia, 9, 26 460–461 syndrome, 369 alobar holoprosencephaly, 494 PTEN hamartoma tumor syndrome, 775–790 Pyloric stenosis: arthrogryposis, 76 dermatologic anomalies, 785 Coffin–Siris syndrome, 191 Beckwith–Wiedemann syndrome, 140 development and behavior problems, 782 Mowat–Wilson syndrome, 603 deletion 5p syndrome, 283 diagnostic criteria, 777–778 Smith–Lemli–Opitz syndrome, deletion 22q11.2 syndrome, 296 diagnostic testing, 779–781 855, 859 Down syndrome, 355, 359–360, 368 differential diagnosis, 781 trisomy 18 syndrome, 951 incontinentia pigmenti, 508 etiology, pathogenesis, and genetics, 778–779 myotonic dystrophy type 1, 617 growth and feeding problems, 782 Quality of life, Alagille syndrome, 36 Phelan–McDermid syndrome, 321 incidence, 775 Quiet baby syndrome, Klinefelter syndrome, Robin sequence, 811 manifestations and management, 782–786 543–544 Presenilin‐1 (PSEN‐1 gene), Down syndrome and neoplasia incidence, 782–783 Alzheimer disease, 359 neurological anomalies, 785–786 R37X mutation, ATR‐X syndrome, 96 Prosody: vascular anomalies, 786 RAD21 gene mutations, Cornelia de Lange Kabuki syndrome, 532 Ptosis: syndrome, 211 Klinefelter syndrome, 544 Aarskog syndrome, 5 RAF1 mutations, Noonan syndrome, 653 Prostaglandins, CHARGE syndrome, 163–164 Cornelia de Lange syndrome, 218 RAI1, Smith–Magenis syndrome, 867–869 Proteus syndrome, 763–773 fetal alcohol spectrum disorders, 415 Rapamycin, tuberous sclerosis complex, 960, 961

0004944829.INDD 1062 9/25/2020 7:13:43 AM INDEX 1063

Ras genes: Robin sequence, 816–817 Robin sequence, 807–821 cardio‐facio‐cutaneous syndrome, 148 Rubinstein–Taybi syndrome, 828, 829–830 craniofacial anomalies, 817–819, 921 Costello syndrome, 226 Sotos syndrome, 907–908 development and behavior problems, 815–816 neurofibromatosis type 1, 640 trisomy 13 and 18 syndromes, 952 diagnostic criteria, 808 Noonan syndrome, 654 tuberous sclerosis complex, 971–972 diagnostic testing, 811–813 RCAN1 gene, Down syndrome and heart Turner syndrome, 988 differential diagnosis, Stickler syndrome, 920 disease, 369 VATER/VACTERL association, 1001–1002 etiology, pathogenesis, and genetics, 808–811 Reactive airway disease, and WAGR Wolf–Hirschhorn syndrome, 275 growth and feeding problems, 814–815 syndrome, 346 Retinal detachment: incidence, 807–808 Recombinant human parathyroid hormone incontinentia pigmenti, 510–511 manifestations and management, 814–819 analog, osteogenesis imperfecta, 697 Loeys–Dietz syndrome, 572 miscellaneous disorders, 811 Renal angiomyolipomas, differential diagnosis, Marfan syndrome, 590 prenatal management, 814 tuberous sclerosis complex, 964 Rett syndrome, 804 respiratory anomalies, 816–817 Renal anomalies: Smith–Magenis syndrome, 884, 885 single gene disorders, 809 Alagille syndrome, 40 Stickler syndrome, 918, 920, 921 teratogenic disorders, 810–811 ATR‐X syndrome, 101 Retinal dysfunction, Rubinstein–Taybi Rombo syndrome, differential diagnosis, Gorlin Bardet–Biedl syndrome, 108, 111, 115–116 syndrome, 829 syndrome, 463 Beckwith–Wiedemann syndrome, 137 Retinal pigmentation, tuberous sclerosis ROR2 gene mutations, Robinow syndrome, 4 CHARGE syndrome, 166 complex, 969 RPS6KA3 gene mutation, Coffin–Lowry deletion 1p36 syndrome, 260 Retinal tumors: syndrome, 173–174, 182 deletion 5p syndrome, 285 trisomy 13 syndrome, 949 Rubinstein–Taybi syndrome, 823–835 deletion 22q11.2 syndrome, 306 tuberous sclerosis complex, 958, 969 anesthesia risks, 832 Denys–Drash syndrome, 347 von Hippel–Lindau syndrome, 1008, cardiovascular anomalies, 830 fetal alcohol spectrum disorders, 417 1010, 1013 dental anomalies, 830 Hermansky–Pudlak syndrome (HPS), 55 Retinitis pigmentosa, Noonan syndrome, 659 dermatologic anomalies, 830–831 Noonan syndrome, 662 Retinoic acid, holoprosencephaly, 490 diagnostic criteria, 823–824 osteogenesis imperfecta, 701 Retinoic‐acid‐induced‐1 (RAI1) gene mutations, diagnostic testing, 826 Proteus syndrome, 769 Smith–Magenis syndrome, 863, 868 differential diagnosis, 826 Smith–Lemli–Opitz syndrome, 859 Retinoids, Gorlin syndrome, 467 Cornelia de Lange syndrome, 212 Sotos syndrome, 909 Rett syndrome, 791–806 Mowat–Wilson syndrome, 601 tuberous sclerosis complex, 970 cardiovascular anomalies, 803 etiology, pathogenesis, and genetics, 824–826 Turner syndrome, 987 dental anomalies, 802–803 gastrointestinal anomalies, 828–829 VATER/VACTERL association, 1002 development and behavior problems, 799–800 genitourinary anomalies, 831 Williams syndrome, 1032 diagnostic criteria, 791–796 growth and feeding problems, 826–827 Renal cell carcinoma: diagnostic testing, 796–797 immunologic conditions, 828 Bardet–Biedl syndrome, 116 differential diagnosis, 797 incidence, 823 PTEN hamartoma tumor syndrome, 784 Angelman syndrome, 65 manifestations and management, 826–832 tuberous sclerosis complex, 970–971 deletion 1p36 syndrome, 255 musculoskeletal anomalies, 831–832 von Hippel–Lindau syndrome, 1006, 1008, inverted duplicated chromosome 15 neoplasia incidence, 832 1010–1011, 1013 syndrome, 518 ophthalmologic anomalies, 829 Respiratory anomalies: Mowat–Wilson syndrome, 601 respiratory anomalies, 829–830 arthrogryposis, 87–88 ear anomalies, 804 Russell–Silver syndrome. See Silver–Russell CHARGE syndrome, 164–165 etiology, pathogenesis, and genetics, 796 syndrome Coffin–Lowry syndrome, 180 gastrointestinal anomalies, 803 Coffin–Siris syndrome, 190 genetic counseling, 797 Sacral dimples: Cohen syndrome, 203 growth and feeding problems, 798–799 ATR‐X syndrome, 102 Costello syndrome, 233 hearing disorders, 804 Phelan–McDermid syndrome, 326, 327 deletion 1p36 syndrome, 258–259 incidence, 791 SADDAN syndrome, differential diagnosis, deletion 5p syndrome, 287 language difficulties, 318 achondroplasia, 11 deletion 22q11.2 syndrome, 303 manifestations and management, Saethre–Chotzen syndrome: Down syndrome, 379 797–804 craniofacial anomalies, 247 hereditary hemorrhagic telangiectasia, musculoskeletal anomalies, 802 development and behavior problems, 247 479–481 neurological anomalies, 800–801 diagnostic criteria, 243–244 inverted duplicated chromosome 15 syndrome, ophthalmologic anomalies, 803–804 diagnostic testing, 246 524 Rhabdomyosarcomas, neurofibromatosis differential diagnosis, 246 Loeys–Dietz syndrome, 572–573 type 1, 640 Rubinstein–Taybi syndrome, 826 Marfan syndrome, 591–592 Rho GTPase family, Aarskog syndrome, 3 etiology, pathogenesis, and genetics, myotonic dystrophy type 1, 620–621 Rib anomalies: 245–246 oculo‐auriculo‐vertebral spectrum, 678–679 Gorlin syndrome, 470 growth and feeding problems, 246 osteogenesis imperfecta, 699–700 osteogenesis imperfecta, 687 musculoskeletal anomalies, 249 Pallister–Hall syndrome, 713 velo‐cardio‐facial syndrome, 307 ophthalmologic anomalies, 249 Phelan–McDermid syndrome, 330 Ring chromosome 22, Phelan–McDermid Sanger sequencing: Prader–Willi syndrome, 753–754 syndrome, 318–320 craniosynostosis syndromes, 246 Proteus syndrome, 768 Robinow syndrome, differential diagnosis, Ehlers–Danlos syndromes, 393 Rett syndrome, 801 Aarskog syndrome, 4 WT1‐related disorders, 342

0004944829.INDD 1063 9/25/2020 7:13:43 AM 1064 INDEX

Scalp hair: Mowat–Wilson syndrome, 603–604 incidence, 837 Costello syndrome, 236 Noonan syndrome, 658 manifestations and management, 843–847 Noonan syndrome, 663 Pallister–Hall syndrome, 711 musculoskeletal anomalies, 845–846 SCARB2 gene mutations, action myoclonus‐renal Pallister–Killian syndrome, 718, 726–727 Simpson–Golabi–Behmel syndrome: failure syndrome, 343 Phelan–McDermid syndrome, 326 differential diagnosis Schaaf–Yang syndrome, differential diagnosis, Prader–Willi syndrome, 750 Beckwith–Wiedemann syndrome, 133 Prader–Willi syndrome, 741 Proteus syndrome, 769 Costello syndrome, 228 Schimke syndrome, differential diagnosis, Rett syndrome, 792, 800 Wilms tumor, 343 WT1‐related disorders, 342 Smith–Magenis syndrome, 882, 884 Simvastin, Smith–Lemli–Opitz syndrome, Schwalbe’s ring, Alagille syndrome, 32 Sotos syndrome, 907 854–855 Schwannomatosis, Coffin–Siris syndrome, 192 trisomy 13 and 18 syndromes, 947 SIX3 gene mutation, holoprosencephaly, 492–493 Sclerocornea, deletion 22q11.2 syndrome, 306 tuberous sclerosis complex, 958–959, 964, Skeletal anomalies. See Musculoskeletal Sclerosis, skull bones, tuberous sclerosis 966, 967 anomalies complex, 972 Wolf–Hirschhorn syndrome, 268, 271–272 Skin anomalies. See Dermatologic anomalies Sclerostin, osteogenesis imperfecta, 697–698 Selective mutism. See Speech disorders Skin cancer risk. See also Dermatologic Scoliosis. See also kyphoscoliosis Selective serotonin reuptake inhibitors (SSRIs), anomalies Angelman syndrome, 70 fragile X syndrome, 447, 449 albinism, 46, 52 arthrogryposis, 85 Self‐injury: oculocutaneous albinism, 47 ATR‐X syndrome, 102 Cornelia de Lange syndrome, 214 Skin picking, Prader–Willi syndrome, 755, 756 Coffin–Siris syndrome, 190 Smith–Magenis syndrome, 865, 874, 883 SLBP gene, Wolf–Hirschhorn syndrome, 268 deletion 5p syndrome, 286 SEMA5A gene, deletion 5p syndrome, 282 SLC24A5 gene, oculocutaneous albinism, 49 Ehlers–Danlos syndromes, 398 Semilobar holoprosencephaly, 487 SLC45A2 gene, oculocutaneous albinism, 49 fragile X syndrome, 452 development and behavior problems, 496 Sleep abnormalities: inverted duplicated chromosome 15 syndrome, diagnostic criteria, 488 Angelman syndrome, 68 524 diagnostic testing, 494 deletion 5p syndrome, 285, 287 Kabuki syndrome, 536 etiology, pathogenesis, and genetics, 492 Down syndrome, 376–377 Loeys–Dietz syndrome, 570 incidence, 487–488 holoprosencephaly, 499 Marfan syndrome, 587, 588 neurological anomalies, 498–499 inverted duplicated chromosome 15 syndrome, neurofibromatosis type 1, 643, 644 Sertraline, fragile X syndrome, 446 520 osteogenesis imperfecta, 695 Severe metabolic bone disease with osteoporosis, Mowat–Wilson syndrome, 602 Pallister–Killian syndrome, 729 Alagille syndrome, 41 myotonic dystrophy type 1, 619 Phelan–McDermid syndrome, 329 Sex hormone replacement, Prader–Willi Phelan–McDermid syndrome, 323 Prader–Willi syndrome, 738, 744, 755 syndrome, 752 Prader–Willi syndrome, 737, 742, 753 Rett syndrome, 802 Sexual development disorders, WT1‐related Rett syndrome, 799 Silver–Russell syndrome, 845, 846 disorders, 340 Smith–Lemli–Opitz syndrome, 856 Smith–Magenis syndrome, 885 Sexual maturation, Down syndrome, 370–371 Smith–Magenis syndrome, 864, 865, 867, Sotos syndrome, 910, 911 Shagreen patches, tuberous sclerosis complex, 874–875, 878–881 trisomy 18 syndrome, 951, 952 968, 969 Williams syndrome, 1026, 1027 VATER/VACTERL association, 999 SHANK3 gene mutation, Phelan–McDermid Wolf–Hirschhorn syndrome, 271 Wolf–Hirschhorn syndrome, 274 syndrome, 317, 320–321 SMAD2 gene mutations, Loeys–Dietz Screaming spells, Rett syndrome, 799, 800 Short stature: See Growth problems syndrome, 565 SDHx gene mutations, von Hippel–Lindau Prader–Willi syndrome, 742 SMAD4 gene mutation, hereditary hemorrhagic syndrome, 1008 Smith–Magenis syndrome, 871 telangiectasia, 476, 483 Seizure disorders. See also Epilepsy Turner syndrome, 980 Small for gestational age: Angelman syndrome, 65, 69, 70 Shoulder hypermobility, achondroplasia, 25 fetal anticonvulsant syndrome, 427, 434 ATR‐X syndrome, 101 SHOX gene: Marfan syndrome, 592 Coffin–Lowry syndrome, 178 47,XXY, 542 Silver–Russell syndrome, 837, 843 Cohen syndrome, 202 Turner syndrome, 980 Smith–Lemli–Opitz syndrome, 855 Cornelia de Lange syndrome, 219 Shprintzen–Goldberg syndrome, differential SMARCA2 gene mutations, Nicolaides–Baraitser Costello syndrome, 234 diagnosis, Loeys–Dietz syndrome, syndrome, 187 deletion 1p36 syndrome, 257 567–568 SMARCA4 gene mutations, Coffin–Siris deletion 5p syndrome, 285 Silver–Russell syndrome, 837–849 syndrome, 190 deletion 22q11.2 syndrome, 304 adulthood, 846–847 SMARCAL1 gene mutations, Schimke syndrome, Down syndrome, 380 and Beckwith–Wiedmann syndrome, 132 342 fetal alcohol spectrum disorders, 418 congenital anomalies, 846 SMARCB1 gene mutations, Coffin–Siris fetal anticonvulsant syndrome, 435 craniofacial anomalies, 845 syndrome, 191 fragile X syndrome, 450 dental anomalies, 845 SMC1A gene mutation, Cornelia de Lange Gorlin syndrome, 471 development and behavior problems, 845 syndrome, 210, 211 Greig cephalopolysyndactyly syndrome, diagnostic criteria, 837–839 SMC3 gene mutation, Cornelia de Lange 713, 714 diagnostic testing, 841 syndrome, 210, 211 holoprosencephaly, 499 differential diagnosis, 841–843 Smith–Lemli–Opitz syndrome, 490, 851–862 inverted duplicated chromosome 15 syndrome, etiology, pathogenesis, and genetics, 839–841 cardiovascular anomalies, 858 520, 522 gastrointestinal anomalies, 844 craniofacial anomalies, 857–858 Kabuki syndrome, 533 growth and feeding problems, 843–844 dermatologic anomalies, 860 management in pregnancy, 438–439 hypoglycemia, 846 development and behavior problems, 856–857

0004944829.INDD 1064 9/25/2020 7:13:43 AM INDEX 1065

diagnostic criteria, 851–852 gastrointestinal anomalies, 911 SPRED1 gene mutations, café‐au‐lait spots, 634 diagnostic testing, 853–854 genetic counseling, 901 SREBF1 gene mutations, Smith–Magenis differential diagnosis, 854 growth and feeding problems, 901–905 syndrome, 870 deletion 22q11.2 syndrome, 298 incidence, 895 Staphylococcal infection, differential diagnosis, Mowat–Wilson syndrome, 601 lymphedema, 909 incontinentia pigmenti, 509 trisomy 13 syndrome, 943 manifestations and management, 901–911 Startled response, exaggerated, Coffin–Lowry etiology, pathogenesis, and genetics, 852–853 musculoskeletal anomalies, 910–911 syndrome, 178 gastrointestinal anomalies, 858–859 neoplasia incidence, 910 Steinert disease. See Myotonic dystrophy genitourinary anomalies, 859–860 neurological anomalies, 907 type 1 growth and feeding problems, 855–856 ophthalmologic anomalies, 908 Steroid‐resistant nephrotic syndrome, WT1‐ incidence, 851 otolaryngologic anomalies, 907–908 related disorders, 335, 343 manifestations and management, 854–860 renal anomalies, 909 Stickler syndrome, 915–925 musculoskeletal anomalies, 860 respiratory anomalies, 907–908 cardiovascular anomalies, 923 neurological anomalies, 857 Wilms tumor, 343 craniofacial anomalies, 921–922 ophthalmologic anomalies, 858 Sound, hypersensitivity to, Williams development and behavior problems, 920 Smith–Magenis syndrome, 863–893 syndrome, 1032 diagnostic criteria, 915–917 cardiovascular anomalies, 885 Spasmodic upper body squeeze (self‐hug), diagnostic testing, 919 craniofacial anomalies, 884 Smith–Magenis syndrome, 867, 874 differential diagnosis, 919–920 dental anomalies, 884 Spastic paraplegia: hypermobile Ehlers‐Danlos syndrome, 396 dermatologic anomalies, 887–888 ATR‐X syndrome, 101 Marfan syndrome, 585 development and behavior problems, 872–878 differential diagnosis, Phelan–McDermid ear anomalies, 922 diagnostic criteria, 864–867 syndrome, 321 etiology, pathogenesis, and genetics, diagnostic testing, 870–871 SPECC1L gene mutations, Teebi hypertelorism 917–919 differential diagnosis, 871 syndrome, 4 genetic counseling, 919 deletion 1p36 syndrome, 255 Speech disorders: see also Cognitive function growth and feeding problems, 920 Down syndrome, 361 achondroplasia, 21 hearing disorders, 922 Phelan–McDermid syndrome, 321 Angelman syndrome, 65, 66, 67, 68 incidence, 915 Williams syndrome, 1024 Coffin–Siris syndrome, 188 manifestations and management, 920–923 endocrine anomalies, 886–887 Cohen syndrome, 200 musculoskeletal anomalies, 922–923 etiology, pathogenesis, and genetics, 867–870 Cornelia de Lange syndrome, 213–214 ophthalmologic anomalies, 920–921 gastrointestinal anomalies, 885 deletion 5p syndrome, 283–284 and Robin sequence, 809, 813 genetic counseling, 870 deletion 22q11.2 syndrome, 300 Stimulus‐induced drop attacks, Coffin–Lowry genitourinary anomalies, 885–886 48,XXYY syndrome, 553 syndrome, 178–179 growth and feeding problems, 871–872 Greig cephalopolysyndactyly syndrome, 713 Strabismus: immunologic conditions, 887 Mowat–Wilson syndrome, 602 albinism, 52 incidence, 863–864 myotonic dystrophy type 1, 618 Angelman syndrome, 70 manifestations and management, 871–888 oculo‐auriculo‐vertebral spectrum, 674 ATR‐X syndrome, 103 musculoskeletal anomalies, 885 Pallister–Killian syndrome, 725 cardio‐facio‐cutaneous syndrome, 152 neurological anomalies, 882–884 Phelan–McDermid syndrome, 318, 322–323 CHARGE syndrome, 163 ophthalmologic anomalies, 884–885 Prader‐Willi syndrome, 744 deletion 1p36 syndrome, 259 otolaryngologic anomalies, 881–882 Rett syndrome, 799 Gorlin syndrome, 469 sleep abnormalities, 878–881 Robin sequence, 819 incontinentia pigmenti, 511 SNF2 protein family, ATR‐X syndrome, 94 Rubinstein–Taybi syndrome, 826 Loeys–Dietz syndrome, 572 SNORD116 gene mutations, Prader–Willi Silver–Russell syndrome, 845 Marfan syndrome, 590 syndrome, 740 Smith–Magenis syndrome, 873, 881 Phelan–McDermid syndrome, 327 Snoring: Treacher Collins syndrome, 931 Prader–Willi syndrome, 738, 752 achondroplasia, 20 Williams syndrome, 1033 Smith–Magenis syndrome, 885 deletion 5p syndrome, 287 Sphenoid wing dysplasia, neurofibromatosis type Williams syndrome, 1031 SNRPN mutations, Angelman syndrome, 64 1, 642–643, 644 Stridor, Cohen syndrome, 203 SOLAMEN syndrome. See Cowden syndrome Spina bifida: Strokes, Smith–Magenis syndrome, 883 Sonic hedgehog (SHH) gene mutation: ATR‐X syndrome, 102 Subdural hematomata, achondroplasia, 18 Gorlin syndrome, 461 Smith–Magenis syndrome, 885 Subependymal giant cell astrocytoma, tuberous holoprosencephaly, 492 Spine anomalies: sclerosis complex, 966, 967 Smith–Lemli–Opitz syndrome, 853 achondroplasia, 23 Subependymal nodules, tuberous sclerosis SOS1 gene mutations, Noonan syndrome, 653 deletion 22q11.2 syndrome, 292 complex, 966 Sotos syndrome, 895–913 Loeys–Dietz syndrome, 569 Sudden death, Williams syndrome, 1030 cardiovascular anomalies, 908–909 neurofibromatosis type 1, 644 Sudden infant death syndrome (SIDS): dental anomalies, 908 Proteus syndrome, 767 achondroplasia, 18 development and behavior problems, 905–907 VATER/VACTERL association, 999–1000 Robin sequence, 816 diagnostic criteria, 895–897 Spleen, absent: SUFU gene mutations, Gorlin syndrome, 462 diagnostic testing, 899–901 ATR‐X syndrome, 103 Sun exposure: differential diagnosis, 901 Mowat–Wilson syndrome, 605 albinism, 52 Beckwith–Wiedemann syndrome, 133 Splenomegaly, Alagille syndrome, 37, 38 Smith–Lemli–Opitz syndrome, 860 Coffin–Lowry syndrome, 175 Spondyloepiphyseal dysplasia, Stickler Supravalvar aortic stenosis syndrome. See etiology, pathogenesis, and genetics, 898–899 syndrome, 916, 922 Williams syndrome

0004944829.INDD 1065 9/25/2020 7:13:43 AM 1066 INDEX

Syndactyly: Thrombocytopenia, trisomy 13 and 18 dental anomalies, 931, 932 Greig cephalopolysyndactyly syndrome, 714 syndromes, 950 development and behavior problems, 930–931 Phelan–McDermid syndrome, 328 Thrombosis, Proteus syndrome, 768 diagnostic criteria, 927–928 Smith–Lemli–Opitz syndrome, 860 Thumb anomalies. See also Hand anomalies diagnostic testing, 813, 929 Syndromic bile duct paucity. See Alagille Gorlin syndrome, 470 differential diagnosis, 929–930 syndrome Rubinstein–Taybi syndrome, 824 oculo‐auriculo‐vertebral spectrum, 673 Syntelencephaly, holoprosencephaly, 487, 489 Smith–Lemli–Opitz syndrome, 860 ear anomalies, 932–933 Thyroid disease: etiology, pathogenesis, and genetics, 928–929 Tachycardia: Down syndrome, 370, 371 growth and feeding problems, 930 Costello syndrome, 232–233 PTEN hamartoma tumor syndrome, hearing disorders, 932–933 fetal anticonvulsant syndrome, 436 783–784, 785 incidence, 927 myotonic dystrophy type 1, 621 Turner syndrome, 987 manifestations and management, 930–933 Tachypnea, achondroplasia, 20 Thyroid‐stimulating hormone (TSH): ophthalmologic anomalies, 932 Tall stature, differential diagnosis, Sotos Bardet–Biedl syndrome, 117 Trichorhinophalangeal syndrome, differential syndrome, 901 Williams syndrome, 1029 diagnosis, Phelan–McDermid Talon cusps, Rubinstein–Taybi syndrome, 830 Tibia varus, achondroplasia, 24 syndrome, 321 Tamoxifen, PTEN hamartoma tumor Tight heel cords, Smith–Magenis syndrome, 886 Triglyceridemia, Alagille syndrome, 32 syndrome, 785 Toe anomalies: Trisomy 8 mosaicism syndrome, differential Tasimelteon, Smith–Magenis syndrome, 879 47,XXY syndrome, 550 diagnosis, Marfan syndrome, 585 TBC1D24 gene mutations, DOORS Grieg cephalopolysyndactyly syndrome, 709 Trisomy 13 syndrome, 937 syndrome, 187 Pallister‐Hall, 708 cardiovascular anomalies, 948–949 TBX1 gene mutations, deletion 22q11.2 Pfeiffer syndrome, 243 development and behavior problems, 946–947 syndrome, 293 Phelan–McDermid syndrome, 328 diagnostic criteria, 942 T‐cell disorders: Rubinstein–Taybi syndrome, 824 diagnostic testing, 943 deletion 22q11.2 syndrome, 305 Smith–Lemli–Opitz syndrome, 852 differential diagnosis, 943 Down syndrome, 379 Smith–Magenis syndrome, 883 Smith–Lemli–Opitz syndrome, 854 TCF4 gene mutation, Rett syndrome, 797 Toenails: ear anomalies, 951 TCOF1 gene mutation, Treacher Collins Phelan–McDermid syndrome, 329 etiology, pathogenesis, and genetics, 942–943 syndrome, 928, 929 tuberous sclerosis complex, 958 gastroenterology anomalies, 950–951 TEB4 gene, deletion 5p syndrome, 282 Toe walking, Smith–Magenis syndrome, 886 genitourinary anomalies, 949–950 Teebi hypertelorism syndrome, differential Toilet training: growth and feeding problems, 945–946 diagnosis, Aarskog syndrome, 4 fragile X syndrome, 452 hearing disorders, 951 Telangiectases, hereditary hemorrhagic Phelan–McDermid syndrome, 323 hematologic anomalies, 950 telangiectasia, 478, 482 Sotos syndrome, 905 holoprosencephaly, 490 Temple syndrome, differential diagnosis, Silver– Tongue anomalies, Angelman syndrome, 67, 68 incidence, 937, 941–942 Russell syndrome, 841 Tonsillar hypertrophy: manifestations and management, 943–952 Temporomandibular joint (TMJ) anomalies: achondroplasia, 21 musculoskeletal anomalies, 951–952 arthrogryposis, 85 Prader–Willi syndrome, 742 neonatal care, 945 Down syndrome, 377 Tonsillectomy, achondroplasia, 21 neoplasia incidence, 950 myotonic dystrophy type 1, 619 Topiramate: neurological anomalies, 947–948 oculo‐auriculo‐vertebral spectrum, 675 fetal anticonvulsant syndrome, 432–433 ophthalmologic anomalies, 949 Tenascin X deficiency, classic‐like Ehlers–Danlos Prader–Willi syndrome, 756 respiratory anomalies, 952 syndrome, 392, 393 Tourette syndrome, with Smith–Magenis Trisomy 18 syndrome, 937–956 Teratogens: syndrome, 875 cardiovascular anomalies, 948–949 fetal anticonvulsant syndrome, 426 Townes–Brock syndrome, differential diagnosis, development and behavior problems, 946–947 holoprosencephaly, 490 oculo‐auriculo‐vertebral spectrum, 673 diagnostic criteria, 938 oculo‐auriculo‐vertebral spectrum, 673 Tracheoesophageal anomalies, CHARGE diagnostic testing, 940–941 Teriparatide, osteogenesis imperfecta, 697 syndrome, 164 differential diagnosis, 941 Testicular cancer, Down syndrome, 383 Tracheoesophageal fistula: Smith–Lemli–Opitz syndrome, 854 Testosterone therapy: oculo‐auriculo‐vertebral spectrum, 679 ear anomalies, 951 49,XXXXY syndrome, 558 trisomy 13 and 18 syndromes, 945 etiology, pathogenesis, and genetics, 938–940 49,XXXXY syndrome, 557 VATER/VACTERL association, 1000 gastroenterology anomalies, 950–951 Klinefelter syndrome, 542–543, 547–548 Tracheomalacia, arthrogryposis, 87 genitourinary anomalies, 949–950 Prader–Willi syndrome, 752 Tracheostomy: growth and feeding problems, 945–946 TGFBR1/2 gene mutations, Marfan achondroplasia, 21 hearing disorders, 951 syndrome, 592 CHARGE syndrome, 164 hematologic anomalies, 950 Thalassemia‐mental retardation. See ATR‐X trisomy 18 syndrome, 952 holoprosencephaly, 490 syndrome Transient myeloproliferative disorder, Down incidence, 937, 938 Thanatophoric dysplasia, differential diagnosis: syndrome, 381 manifestations and management, 943–952 achondroplasia, 11 Transient neonatal diabetes mellitus, Beckwith– musculoskeletal anomalies, 951–952 osteogenesis imperfecta, 693 Wiedemann syndrome, 131 neoplasia incidence, 950 Thoracic aortic aneurysm, differential diagnosis: Treacher Collins syndrome, 927–935 neurological anomalies, 947–948 Loeys–Dietz syndrome, 568 anesthetic risks, 933 ophthalmologic anomalies, 949 Marfan syndrome, 585 association with Robin sequence, 809 prenatal diagnosis, 938, 940 Thoracolumbosacral orthosis, achondroplasia, 23 craniofacial anomalies, 931–932 respiratory anomalies, 952

0004944829.INDD 1066 9/25/2020 7:13:43 AM INDEX 1067

Trisomy 21, Down syndrome, 355, 358, 359 Beckwith–Wiedemann syndrome, 127, deletion 5p syndrome, 284 TSC1/TSC2 gene, tuberous sclerosis complex, 130–131, 132 Gorlin syndrome, 469 960, 962 Prader–Willi syndrome, 735, 739 myotonic dystrophy type 1, 622 Tuberin, tuberous sclerosis complex, 960, 961 Silver‐Russell syndrome, 837, 841, 845 neurofibromatosis type 1, 639 Tuberous sclerosis complex, 957–976 Urological anomalies. See genitourinary Phelan–McDermid syndrome, 327 cardiovascular anomalies, 969–970 anomalies Rubinstein–Taybi syndrome, 828, 829 dental anomalies, 972 Smith–Magenis syndrome, 884 dermatologic anomalies, 968–969 Vagal nerve stimulation, tuberous sclerosis Stickler syndrome, 920–921 development and behavior problems, 964–965 complex, 967 Turner syndrome, 989 diagnostic criteria, 957–960 Valproate: Vismodegib, Gorlin syndrome, 467 diagnostic testing, 963 fetal anticonvulsant syndrome, 426, 427 Vitamin A: differential diagnosis, 963–964 fetal valproate syndrome, 429–431 Alagille syndrome, 38 Gorlin syndrome, 463 fragile X syndrome, 450 Robin sequence, 810 etiology, pathogenesis, and genetics, 960–962 during pregnancy, 438 Treacher Collins syndrome, 929 genetic counseling, 962–963 Varicose veins: Vitamin D: genitourinary anomalies, 970–971 Klinefelter syndrome, 552 Down syndrome, 373 growth and feeding problems, 964 Loeys–Dietz syndrome, 573 osteogenesis imperfecta, 701 incidence, 957 Varus deformity, achondroplasia, 24–25 Prader–Willi syndrome, 755 manifestations and management, 964–972 Vascular anomalies: Vitamin E, Smith–Lemli–Opitz syndrome, neurological anomalies, 965–968 neurofibromatosis type 1, 645 858–859 ophthalmologic anomalies, 969 PTEN hamartoma tumor syndrome, 786 Vitamin K: prenatal diagnosis, 969 Vascular endothelial growth factor, von Hippel– carbamazepine embryopathy, clotting respiratory anomalies, 971–972 Lindau syndrome, 1006 issues, 432 Tumor necrosis factor: VATER/VACTERL association, 995–1004 fetal anticonvulsant syndrome, 433, 438 incontinentia pigmenti, 508 cardiovascular anomalies, 999 Vitiligo, differential diagnosis, tuberous sclerosis Smith–Magenis syndrome, 869–870 development and behavior problems, 998–999 complex, 963 Tumors. See Neoplasia diagnostic testing, 996–997 Voice anomalies. See Speech disorders Turner syndrome, 977–994 differential diagnosis, 997 Volvulus, ATR‐X syndrome, 100 cardiovascular anomalies, 981–983 Alagille syndrome, 35 Vomiting episodes, Phelan–McDermid care coordination, 990 deletion 22q11.2 syndrome, 298 syndrome, 329 dental anomalies, 989 etiology, pathogenesis, and genetics, 995–996 Von Hippel–Lindau syndrome, 1005–1020 dermatologic anomalies, 990 gastrointestinal anomalies, 1000–1001 development and behavior problems, development and behavior problems, 985–987 genitourinary anomalies, 1002 1009–1010 diagnostic criteria, 977–978 growth and feeding problems, 998 diagnostic criteria, 1006 diagnostic testing, 978–980 incidence, 995 diagnostic testing, 1007 differential diagnosis, 980 manifestations and management, 997–1002 differential diagnosis, 1007–1009 Noonan syndrome, 654 musculoskeletal anomalies, 999–1000 etiology, pathogenesis, and genetics, ear anomalies, 989 renal anomalies, 1002 1006–1007 endocrine anomalies, 987–988 respiratory anomalies, 1001–1002 gastrointestinal anomalies, 1014–1015 etiology, pathogenesis, and genetics, 978 Velo‐cardio‐facial syndrome, 291. See also genitourinary anomalies, 1015 gastrointestinal anomalies, 988–989 Deletion 22q11.2 syndrome growth and feeding problems, 1009 growth and feeding problems, 980–981 differential diagnosis incidence, 1005–1006 hearing disorders, 989 Phelan–McDermid syndrome, 321 manifestations and management, 1009–1015 immunologic conditions, 987 Williams syndrome, 1024 neoplasia incidence, 1010–1014 incidence, 977 Velopharyngeal incompetence, deletion 22q11.2 Von Recklinghausen disease. See liver dysfunction, 988–989 syndrome, 302 Neurofibromatosis type 1 lymphatic disorders, 983–984 Verloes criteria, CHARGE syndrome, 158 Von Willebrand disease, Noonan syndrome, 660 manifestations and management, 980–990 Very low‐density lipoprotein (VLDL), Smith– VPS13B gene mutations, Cohen syndrome, 197, neoplasia incidence, 343, 990 Magenis syndrome, 870 198, 199 ophthalmologic anomalies, 989 Vestibular anomalies, CHARGE syndrome, 165 respiratory anomalies, 988 VHL gene mutation, von Hippel–Lindau Wagner syndrome, differential diagnosis, Stickler urological anomalies, 987 syndrome, 1006, 1007 syndrome, 919 TWIST gene mutation, craniosynostosis Vigabatrin, tuberous sclerosis complex, 967 WAGR syndrome, 335 syndromes, 245–246 Virchow–Robin spaces, Coffin–Lowry development and behavior problems, 344–345 Typus Degenerativus Amstelodamensis. See syndrome, 178 diagnostic criteria, 336 Cornelia de Lange syndrome Visceromegaly, Beckwith–Wiedemann differential diagnosis, 342 TYR gene, oculocutaneous albinism, 49 syndrome, 136 etiology, pathogenesis, and genetics, 339 TYRP1 gene mutations, 49 Vision impairment: genitourinary anomalies, 347 Aarskog syndrome, 5 gonadoblastoma, 349 UBE3A gene mutations, Angelman syndrome, 61, albinism, 52 growth and feeding problems, 343–344 62, 63, 64 ATR‐X syndrome, 103 incidence, 335 Ulcerative colitis, Turner syndrome, 988 Bardet–Biedl syndrome, 114 musculoskeletal anomalies, 345 Ultraviolet exposure, and albinism, 52 CHARGE syndrome, 158, 162–163 neoplasia incidence, 348–349 Uniparental disomy: Coffin–Siris syndrome, 191 nephropathy, 347–348 Angelman syndrome, 62 Cohen syndrome, 201 neurological anomalies, 344–345

0004944829.INDD 1067 9/25/2020 7:13:43 AM 1068 INDEX

WAGR syndrome (cont’d) ophthalmologic anomalies, 1031–1032 diagnostic testing, 341–342 ophthalmologic anomalies, 345 Wilms tumor: differential diagnosis, 342–343 pulmonary problems, 346 Beckwith–Wiedemann syndrome, 138, 343 ear anomalies, 345 Watson syndrome, differential diagnosis: Denys–Drash/Frasier syndrome, 348 etiology, pathogenesis, and genetics, 339–341 neurofibromatosis type 1, 635 Meacham syndrome, 341 genetic counseling, 342 Noonan syndrome, 654 Perlman syndrome, 343 genitourinary anomalies, 346–348 Weaver syndrome: Phelan–McDermid syndrome, 330 growth and feeding problems, 343–344 differential diagnosis, Beckwith–Wiedemann Sotos syndrome, 343 hearing disorders, 345 syndrome, 133 trisomy 13 syndrome, 950 incidence, 335–336 and Sotos syndrome, 898 trisomy 18 syndrome, 950 manifestations and management, 343–349 Weissenbacher–Zweymuller syndrome: WAGR syndrome, 348 musculoskeletal anomalies, 345 differential diagnosis, Stickler syndrome, WT1‐related disorders, 335, 336, 337, 341, neoplasia incidence, 343, 348–349 919, 920 348–349 neurological anomalies, 344–345 Werner syndrome, differential diagnosis, PTEN WNT1 gene, osteogenesis imperfecta, 691 ophthalmologic anomalies, 345–346 hamartoma tumor syndrome, 781 WNT5A gene mutations, Aarskog syndrome, 4 pulmonary anomalies, 346 Wiedemann–Steiner syndrome, differential Wolfflin–Kruckmann spots, Smith–Magenis diagnosis, Cornelia de Lange syndrome, syndrome, 884 Xanthomas: 212 Wolf–Hirschhorn syndrome, 265–280 Alagille syndrome, 37 Wildervanck syndrome, differential diagnosis, adulthood, 276 Noonan syndrome, 663 oculo‐auriculo‐vertebral spectrum, 673 cardiovascular anomalies, 272–273 X‐linked disorders: Williams–Beuren syndrome. See Williams dental anomalies, 274 Aarskog syndrome, 3 syndrome dermatologic anomalies, 275 albinism, 47 Williams syndrome, 1021–1038 development and behavior problems, 270–271 ATR‐X syndrome, 94 cardiovascular anomalies, 1030–1031 diagnostic criteria, 266–267 Coffin–Lowry syndrome, 171–184 dental anomalies, 1033–1034 diagnostic testing, 269 fragile X syndrome, 444, 446 dermatologic anomalies, 1032 differential diagnosis, 269–270 incontinentia pigmenti, 505–514 development and behavior problems, Pallister–Killian syndrome, 722 Kabuki syndrome, 531 1025–1028 ear anomalies, 273–274 Lujan–Fryns syndrome, 586 diagnostic criteria, 1021–1022 etiology, pathogenesis, and genetics, 267–269 X‐linked dominant chondrodysplasia punctata, diagnostic testing, 1023 gastroenterology anomalies, 275 differential diagnosis, incontinentia differential diagnosis, 1023–1024 genitourinary anomalies, 273 pigmenti, 509 Angelman syndrome, 65 growth and feeding problems, 270 X‐linked hypohidrotic ectodermal Coffin–Lowry syndrome, 175 hearing disorders, 273–274 dysplasia, incontinentia pigmenti and, 508 fetal anticonvulsant syndrome, 428 immunologic conditions, 275 X‐linked α‐thalassemia/mental retardation. See Phelan–McDermid syndrome, 321 incidence, 265 ATR‐X syndrome ear anomalies, 1032 manifestations and management, 270–276 XX females: endocrine anomalies, 1029–1030 musculoskeletal anomalies, 274–275 Denys–Drash/Frasier syndrome, 336 etiology, pathogenesis, and genetics, neoplasia incidence, 275–276 WAGR syndrome, 349 1022–1023 neurological anomalies, 271–272 XY gonadal dysgenesis, Frasier syndrome, 335 gastrointestinal anomalies, 1031 ophthalmologic anomalies, 274 genitourinary anomalies, 1032–1033 respiratory anomalies, 275 ZEB2 gene mutation: growth and feeding problems, Wrist hypermobility: Angelman syndrome, 66 1024–1025 achondroplasia, 25 Mowat–Wilson syndrome, 598, 599, 600 hearing disorders, 1032 Costello syndrome, 233 Zellweger syndrome, differential diagnosis, incidence, 1021 WT1‐related disorders, 335–354 Down syndrome, 361 manifestations and management, 1024–1034 cardiovascular anomalies, 346 ZIC2 gene mutation, holoprosencephaly, 492, 497 musculoskeletal anomalies, 1033 development and behavior problems, 344–345 ZIC3 gene mutation, VATER/VACTERL neurological anomalies, 1028–1029 diagnostic criteria, 336–338 association, 996

0004944829.INDD 1068 9/25/2020 7:13:44 AM