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11 Selected Syndromes and Associations 11 Selected Syndromes and Associations ĭ Apert Syndrome Definition: Also known as acrocephalic syndac- Other anomalies of the cardiac, renal, and tyly syndrome. It is characterized by a “tower- gastrointestinal systems may also be present. shaped” head, facial dysmorphism, and sym- metrical syndactyly of the fingers and toes. Ultrasound findings: The earliest prenatal diag- nosis was possible at 12 weeks of gestation with Incidence: about one in 100 000 births. nuchal translucency measurements. Syndactyly First described in 1906 by Apert. could also be detected at this stage. At a later stage, an unusual shape of the head resulting Etiology/genetics: Partly autosomal-dominant from premature closure of the cranial sutures inheritance, but frequently sporadic occurrence (tower-shaped head) and facial dysmorphism (new mutation). Advanced paternal age is a fac- (hypoplasia of the midfacial region) are charac- tor favoring its occurrence. Gene defect in the fi- teristic features. Detailed scanning may also re- broblast growth factor receptor-2 gene (FGFR2), veal deep-set ears, unusual shape of the nose, gene locus: 10q26. exophthalmos, and hypertelorism. Clinical features: “Tower-shaped” head, early Differential diagnosis: Carpenter syndrome, closure of cranial sutures, anomalies of the cervi- Crouzon syndrome, cloverleaf skull anomaly, cal vertebral column. Facial anomalies: denting Pfeiffer syndrome, thanatophoric dysplasia, of the forehead in the supraorbital region, hyper- achondrogenesis, Cornelia de Lange syndrome, telorism, flat orbital bone, exophthalmos, squint, EEC syndrome, Fryns syndrome, Joubert syn- deep-set ears, small, beak-shaped nose, syndac- drome, multiple pterygium syndrome, Noonan tyly (as extreme as “spoon hands”), fusion of the syndrome, Roberts syndrome, Smith–Lemli– bony parts of fingers II–IV, short fingers, possibly Opitz syndrome, trisomy 21. 1 short upper extremities. Mental impairment is Ī not obligatory; in 80% of cases, the intelligence Clinical management: Further ultrasound quotient lies above 50–70, and often it is normal. screening including fetal echocardiography. 2 Fig. 11.1 Apert syndrome. Fetal profile at Ī 22 + 6 weeks. The striking feature is the high and prominent forehead. Ī3 Ī4 Ī5 236 APERT SYNDROME Karyotyping (differential diagnosis), molecular- genetic evidence of the defective gene. Prognosis: This depends on the extent of mental impairment and the associated organ anomalies. The mortality is increased in the first year of life. Self-Help Organization Title: Apert Syndrome Pen Pals Description: Group correspondence program for persons with Apert syndrome to share ex- perience. Information and referrals, pen pals, phone help. Scope: National network Founded: 1992 Address: P.O. Box 115, Providence, RI 02901, United States Telephone: 401–454–0704 (after 4: 30 p.m.) Fig. 11.2 Apert syndrome. Profile of a child with Title: Apert Support and Information Network Apert syndrome. Description: Provides information and sup- port to families and individuals facing the challenge of Apert syndrome. Provides infor- Address: P.O. Box 1184, Fair Oaks, CA 95628, mation and referrals, newsletter, phone sup- United States port network, pen pals, and annual family get- Telephone: 916–961–1092 togethers. Fax: 916–961–1092 Scope: International network E-mail: [email protected] Founded: 1995 Ĩ Fig. 11.3 Apert syndrome. Syndactyly of the hand, seen at 22 + 6 weeks. Ĩ Ĩ Ĩ4 Ĩ 237 SELECTED SYNDROMES AND ASSOCIATIONS Fig. 11.4 Apert syndrome. Syndactyly of the foot at 22 + 6 weeks. Fig. 11.5 Apert syndrome. Foot of a newborn in- fant with Apert syndrome. Ī1 2 Ī References Lyu KJ, Ko TM. Prenatal diagnosis of Apert syndrome Ferreira JC, Carter SM, Bernstein PS, et al. Second- with widely separated cranial sutures. Prenat Diagn trimester molecular prenatal diagnosis of sporadic 2000; 20: 254–6. Apert syndrome following suspicious ultrasound Mahieu-Caputo D, Sonigo P, Amiel J, et al. Prenatal diag- findings. Ultrasound Obstet Gynecol 1999; 14: 426– nosis of sporadic Apert syndrome: a sequential diag- 3 30. nostic approach combining three-dimensional com- Filkins K, Russo IF, Boehmer S, et al. Prenatal ultrasono- puted tomography and molecular biology. Fetal Ī Diagn Ther 2001; 16: 10–2. graphic and molecular diagnosis of Apert syndrome. Prenat Diagn 1997; 17: 1081–4. Narayan H, Scott IV. Prenatal ultrasound diagnosis of Hafner E, Sterniste W, Scholler J, Schuchter K, Philipp K. Apert’s syndrome. Prenat Diagn 1991; 11: 187–92. Prenatal diagnosis of facial malformations. Prenat Witters I, Devriendt K, Moerman P, van Hole C, Fryns JP. 4 Diagn 1997; 17: 51–8. Diaphragmatic hernia as the first echographic sign in Hill LM, Thomas ML, Peterson CS. The ultrasonic detec- Apert syndrome. Prenat Diagn 2000; 20: 404–6. Ī tion of Apert syndrome. J Ultrasound Med 1987; 6: 601–4. Kaufmann K, Baldinger S, Pratt L. Ultrasound detection of Apert syndrome: a case report and literature re- Ī5 view. Am J Perinatol 1997; 14: 427–30. 238 BECKWITH–WIEDEMANN SYNDROME ĭ Beckwith–Wiedemann Syndrome Definition: This is a metabolic dysplasia syn- development may be adequate as long as dam- drome with omphalocele, macroglossia, en- age to the brain tissue due to hypoglycemia can largement of organs, giantism, ear malforma- be avoided (the tendency to hypoglycemia can tion, and hypoglycemia in the postnatal stage. continue into the first years of life). Hypertrophy There is an increased incidence of blastoma in of the viscera regresses in the course of develop- childhood, especially Wilms tumor and ment. Body size may be normal. Regular checks adrenocortical cancers. are necessary in the first 6 years of life for early detection of blastomas. Incidence: One in 12 000–50 000 births. First described in 1965 by Beckwith and Self-Help Organization Wiedemann. Title: Beckwith–Wiedemann Support Net- work Clinical history/genetics: Heterogeneous syn- drome. Gene locus: 11p15.5. The cause is dys- Description: Support and information for regulation of a parental gene (genomic imprint- parents of children with Beckwith– ing), which affects growth. Eighty-five percent of Wiedemann syndrome or isolated hemihy- cases are sporadic, and 15% are of autosomal- pertrophy, and interested medical profession- dominant inheritance. In some cases of domi- als. Newsletter, parent directory, information nant inheritance, mutation of the cyclin-de- and referrals, phone support. Aims to increase pendent kinase inhibitor 1 C (p57, Kip2) gene public awareness and encourages research. (CDKN1 C) is present. In the sporadic form, chro- Scope: International network mosomal aberrations are present in 1% of cases. Another 10–20% show paternal disomy 11; this Founded: 1989 means that the 11p15 region of both chromo- Address: 2711 Colony Rd., Ann Arbor, MI somes originates from the father and that mater- 48104, United States nal alleles are not present. Some patients de- monstrate mutation of the KVLQT1 gene and, as Telephone: 734–973–0263; parents’ toll-free in the case of dominant inheritance, of the number 1–800–837–2976 CDKN1 C gene. In 50% of cases, an imprinting Fax: 734–973–9721 mutation is seen in which expression of the in- sulin-like growth factor-2 gene (IGF2) is also de- E-mail: [email protected] Ĩ termined by a maternal allele. Web: http://www.beckwith-wiedemann.org Ultrasound findings: Macrosomia is evident in the later stages of the second trimester. Other features are: hydramnios, anomalies of the References Ĩ placenta such as partial molar degeneration, Cobellis G, Iannoto P, Stabile M, et al. Prenatal ultra- macroglossia, hypertrophy of organs, especially sound diagnosis of macroglossia in the Wiedemann– Beckwith syndrome. Prenat Diagn 1988; 8: 79–81. large and echogenic kidneys, cardiomyopathy Fert-Ferrer S, Guichet A, Tantau J, et al. Subtle familial and cardiomegaly, and omphalocele. In addition, unbalanced translocation t(8; 11)(p23.2;p15.5) in cryptorchism and hypospadias may also be evi- two fetuses with Beckwith–Wiedemann features. Ĩ dent. Detection has been reported as early as at Prenat Diagn 2000; 20: 511–5. Fremond B, Poulain P, Odent S, Milon J, Treguier C, Babut 12 weeks of gestation. JM. Prenatal detection of a congenital pancreatic cyst and Beckwith–Wiedemann syndrome. Prenat Diagn Differential diagnosis: Diabetic fetopathy, Perl- 1997; 17: 276–80. 4 man syndrome, Simpson–Golabi–Behmel syn- Hamada H, Fujiki Y, Obata-Yasuoka M, Watanabe H, Ya- mada N, Kubo T. Prenatal sonographic diagnosis of Ĩ drome, Marfan syndrome, Marshall–Smith syn- Beckwith–Wiedemann syndrome in association drome, Sotos syndrome, Weaver syndrome. with a single umbilical artery. J Clin Ultrasound 2001; 29: 535–8. Prognosis: The perinatal fatality is about 20% Hewitt B, Bankier A. Prenatal ultrasound diagnosis of Beckwith–Wiedemann syndrome. Aust N Z J Obstet and is due to macrosomia, omphalocele, hy- Gynaecol 1994; 34: 488–90. Ĩ poglycemia, fits, and cardiac failure. Mental 239 SELECTED SYNDROMES AND ASSOCIATIONS Koontz WL, Shaw LA, Lavery JP. Antenatal sonographic Viljoen DL, Jaquire Z, Woods DL. Prenatal diagnosis in appearance of Beckwith–Wiedemann syndrome. autosomal-dominant Beckwith–Wiedemann syn- JCU J Clin Ultrasound 1986; 14: 57–9. drome. Prenat Diagn 1991; 11: 167–75. Nowotny T, Bollmann R, Pfeifer L, Windt E. Beckwith– Whisson CC, Whyte A, Ziesing P Beckwith–Wiedemann Wiedemann syndrome: difficulties with prenatal di- syndrome: antenatal diagnosis. Australas Radiol agnosis. Fetal Diagn Ther 1994; 9: 256–60. 1994; 38: 130–1. Reish O, Lerer I, Amiel A, et al.
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