DOCSLIB.ORG

Blueprint Genetics Skeletal Dysplasias Core Panel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Skeletal Dysplasias Core Panel Test code: MA3501 Is a 113 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of a skeletal dysplasia. The genes on this panel are included in the Comprehensive Skeletal Dysplasias and Disorders Panel and in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel. About Skeletal Dysplasias Core The Skeletal Dysplasias Core Panel is designed to detect mutations responsible for various skeletal dysplasias. Some of the resulting skeletal dysplasias are severe and potentially lethal (such as thanatophoric dysplasia, different types of achondrogenesis and osteogenesis imperfecta type II). Other non-lethal skeletal dysplasias result in disproportionate short stature. Achondroplasia is the most common cause of disproportionate short stature worldwide. It is characterized by rhizomelic shortening of the limbs, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia. Type II collagen defects (mutations in COL2A1 genes) have been identified in a spectrum of disorders ranging from perinatally lethal conditions to those with only mild arthropathy. As many different skeletal dysplasias have similar clinical and radiological findings, multigene panel testing allows for efficient diagnostic testing. Identification of causative mutation(s) establishes the inheritance mode in the family and enables genetic counselling. In addition, identifying the causative mutation(s) provides essential information for the doctor taking care of the patient. This panel provides excellent diffential diagnostic power for the major genes causing skeletal dysplasias. Availability 4 weeks Gene Set Description Genes in the Skeletal Dysplasias Core Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACAN# Spondyloepimetaphyseal dysplasia, aggrecan type, AD/AR 20 56 Spondyloepiphyseal dysplasia, Kimberley type, Osteochondritis dissecans, short stature, and early-onset osteoarthritis ACP5 Spondyloenchondrodysplasia with immune dysregulation AR 12 26 ADAMTS10 Weill-Marchesani syndrome AR 8 14 ADAMTSL2*,# Geleophysic dysplasia 3 AR 8 28 AGPS Rhizomelic chondrodysplasia punctata type 3 AR 4 8 ALPL Odontohypophosphatasia, Hypophosphatasia perinatal AD/AR 78 291 lethal, infantile, juvenile and adult forms ANKH Calcium pyrophosphate deposition disease (familial AD 13 20 chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type ARSE* Chondrodysplasia punctata X-linked recessive, XL 22 46 brachytelephalangic type (CDPX1) https://blueprintgenetics.com/ B3GALT6 Spondyloepimetaphyseal dysplasia with joint laxity, AR 17 27 Ehlers-Danlos syndrome BMP1 Osteogenesis imperfecta AR 7 21 BMPR1B Acromesomelic dysplasia, Demirhan, Brachydactyly AD/AR 12 23 C/Symphalangism-like pheno, Brachydactyly type A2, Pulmonary arterial hypertension (PAH) CA2 Osteopetrosis, with renal tubular acidosis AR 9 31 CANT1 Desbuquois dysplasia AR 20 28 CDC6 Meier-Gorlin syndrome (Ear-patella-short stature AR 2 2 syndrome) CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 35 81 CDT1 Meier-Gorlin syndrome (Ear-patella-short stature AR 6 12 syndrome) CHST3 Spondyloepiphyseal dysplasia with congenital joint AR 18 37 dislocations (recessive Larsen syndrome) CLCN7 Osteopetrosis AD/AR 15 98 COL10A1 Metaphyseal chondrodysplasia, Schmid AD 21 53 COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler AD/AR 34 94 syndrome type 2 COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, AD/AR 29 57 Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non- ocular) COL1A1 Ehlers-Danlos syndrome, Caffey disease, Osteogenesis AD 352 962 imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 COL1A2 Ehlers-Danlos syndrome, cardiac valvular form, AD/AR 186 509 Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 COL2A1 Avascular necrosis of femoral head, Rhegmatogenous AD 180 561 retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 COL9A1 Stickler syndrome recessive type, Multiple epiphyseal AD/AR 9 6 dysplasia type 6 (EDM6) COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 AD/AR 7 12 (EDM2) https://blueprintgenetics.com/ COL9A3 Multiple epihyseal dysplasia type 3 (EDM3), Stickler AD/AR 10 14 syndrome recessive type COMP Pseudoachondroplasia, Multiple ephiphyseal dysplasia AD 43 186 CRTAP Osteogenesis imperfecta type 2, Osteogenesis imperfecta AR 12 30 type 3, Osteogenesis imperfecta type 4 CSPP1 Jeune asphyxiating thoracic dystrophy, Joubert syndrome AR 32 27 CTSK Pycnodysostosis AR 35 58 CUL7 3-M syndrome, Yakut short stature syndrome AR 26 83 CYP27B1 Vitamin D-dependent rickets AR 23 73 DHCR24 Desmosterolosis AR 6 9 DLL3 Spondylocostal dysostosis AR 12 26 DVL1 Robinow syndrome AD 17 19 DYM Dyggve-Melchior-Clausen dysplasia, Smith-McCort AR 22 34 dysplasia DYNC2H1 Short -rib thoracic dysplasia with or without polydactyly AR/Digenic 148 205 type 1, Short -rib thoracic dysplasia with or without polydactyly type 3, Asphyxiating thoracic dysplasia (ATD; Jeune), SRPS type 2 (Majewski) EBP Chondrodysplasia punctata, Male EBP disorder with XL 43 90 neurologic defects (MEND) EIF2AK3 SED, Wolcott-Rallison type AR 9 80 ENPP1 Arterial calcification, Hypophosphatemic rickets AD/AR 22 72 ESCO2 SC phocomelia syndrome, Roberts syndrome AR 30 31 EVC Weyers acrofacial dysostosis, Ellis-van Creveld syndrome AD/AR 58 83 EVC2 Ellis-van Creveld syndrome, Weyers acrodental dysostosis AD/AR 78 75 FAM20C Hypophosphatemia, hyperphosphaturia, dental anomalies, AR 13 25 intracerebral calcifications and osteosclerosis (Raine syndrome) FGF23 Tumoral calcinosis, hyperphosphatemic, AD/AR 10 17 Hypophosphatemic rickets FGFR1 Pfeiffer syndrome, Trigonocephaly, Hypogonadotropic AD/Digenic/Multigenic 72 257 hypogonadism, Osteoglophonic Dwarfism - Craniostenosis, Hartsfield syndrome FGFR2 Apert syndrome, Pfeiffer syndrome, Jackson-Weiss AD 100 154 syndrome, Lacrimoauriculodentodigital syndrome, Beare- Stevenson cutis gyrata syndrome, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, Craniofacial-skeletal-dermatological dysplasia, Crouzon syndrome, Bent bone dysplasia https://blueprintgenetics.com/ FGFR3 Lacrimoauriculodentodigital syndrome, Muenke AD/AR 54 77 syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN FKBP10 Bruck syndrome 1, Osteogenesis imperfecta, type XI AR 20 44 FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick- XL 133 257 Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects FLNB Larsen syndrome (dominant), Atelosteogenesis type 1, AD/AR 43 121 Atelosteogenesis type 3, Spondylo-carpal-tarsal dyspasia GDF5 Multiple synostoses syndrome, Fibular hypoplasia and AD/AR 23 53 complex brachydactyly, Acromesomelic dysplasia, Hunter- Thompson, Symphalangism, proximal, Chondrodysplasia, Brachydactyly type A2, Brachydactyly type C, Grebe dysplasia GNPAT Rhizomelic chondrodysplasia punctata, rhizomelic AR 8 14 HSPG2 Schwartz-Jampel syndrome, Dyssegmental dysplasia AD/AR 16 60 Silverman-Handmaker type, Dyssegmental dysplasia Rolland-Desbuquis type IFT140 Short -rib thoracic dysplasia with or without polydactyly, AR 38 63 Asphyxiating thoracic dysplasia (ATD; Jeune) IFT172 Retinitis pigmentosa, Short -rib thoracic dysplasia with or AR 22 25 without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) IFT80 Short -rib thoracic dysplasia with or without polydactyly, AR 11 11 Asphyxiating thoracic dysplasia (ATD; Jeune) IHH Acrocapitofemoral dysplasia, Brachydactyly, Syndactyly AD/AR 12 32 type Lueken INPPL1 Opsismodysplasia AR 16 32 KAT6B Ohdo syndrome, SBBYS variant, Genitopatellar syndrome AD 47 73 LBR Pelger-Huet anomaly, Reynolds syndrome, AD/AR 22 24 Greenberg/HEM skeletal dysplasia, Hydrops-ectopic calcification-moth-eaten skeletal dysplasia LIFR Stuve-Wiedemann dysplasia, Schwartz-Jampel type 2 AR 12 32 syndrome LMX1B Nail-patella syndrome AD 26 194 LRP5* Van Buchem disease, Osteoporosis-pseudoglioma AD/AR/Digenic 57 196 syndrome, Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosis https://blueprintgenetics.com/ LTBP2 Weill-Marchesani syndrome, Microspherophakia and/or AR 21 27 megalocornea, with ectopia lentis and with or without secondary glaucoma, Glaucoma, primary congenital MATN3 Spondyloepimetaphyseal dysplasia Matrilin type, Multiple AD/AR 8 25 epiphyseal dysplasia type 5 (EDM5) MMP9 Metaphyseal anadysplasia AR 1 7 MYO18B Klippel-Feil syndrome 4, autosomal recessive, with AR 2 4 myopathy and facial dysmorphism NEK1 Short -rib thoracic dysplasia with or without polydactyly, AR/Digenic 22 23 SRPS type 2 (Majewski) NPR2 Acromesomelic dysplasia type Maroteaux, Epiphyseal AD/AR 32 75 chondrodysplasia, Miura, Short stature with nonspecific
Recommended publications
  • Prestin, a Cochlear Motor Protein, Is Defective in Non-Syndromic Hearing Loss

    Prestin, a Cochlear Motor Protein, Is Defective in Non-Syndromic Hearing Loss

    Human Molecular Genetics, 2003, Vol. 12, No. 10 1155–1162 DOI: 10.1093/hmg/ddg127 Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss Xue Zhong Liu1,*, Xiao Mei Ouyang1, Xia Juan Xia2, Jing Zheng3, Arti Pandya2, Fang Li1, Li Lin Du1, Katherine O. Welch4, Christine Petit5, Richard J.H. Smith6, Bradley T. Webb2, Denise Yan1, Kathleen S. Arnos4, David Corey7, Peter Dallos3, Walter E. Nance2 and Zheng Yi Chen8 1Department of Otolaryngology, University of Miami, Miami, FL 33101, USA, 2Department of Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0033, USA, 3Department of Communication Sciences and Disorders, Auditory Physiology Laboratory (The Hugh Knowles Center), Northwestern University, Evanston, IL, USA, 4Department of Biology, Gallaudet University, Washington, DC 20002, USA, 5Unite´ de Ge´ne´tique des De´ficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, France, 6Department of Otolaryngology University of Iowa, Iowa City, IA 52242, USA, 7Neurobiology Department, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, USA and 8Department of Neurology, Massachusetts General Hospital and Neurology Department, Harvard Medical School Boston, MA 02114, USA Received January 14, 2003; Revised and Accepted March 14, 2003 Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4 ) are associated with different human hereditary diseases.
  • Repercussions of Inborn Errors of Immunity on Growth☆ Jornal De Pediatria, Vol

    Repercussions of Inborn Errors of Immunity on Growth☆ Jornal De Pediatria, Vol

    Jornal de Pediatria ISSN: 0021-7557 ISSN: 1678-4782 Sociedade Brasileira de Pediatria Goudouris, Ekaterini Simões; Segundo, Gesmar Rodrigues Silva; Poli, Cecilia Repercussions of inborn errors of immunity on growth☆ Jornal de Pediatria, vol. 95, no. 1, Suppl., 2019, pp. S49-S58 Sociedade Brasileira de Pediatria DOI: https://doi.org/10.1016/j.jped.2018.11.006 Available in: https://www.redalyc.org/articulo.oa?id=399759353007 How to cite Complete issue Scientific Information System Redalyc More information about this article Network of Scientific Journals from Latin America and the Caribbean, Spain and Journal's webpage in redalyc.org Portugal Project academic non-profit, developed under the open access initiative J Pediatr (Rio J). 2019;95(S1):S49---S58 www.jped.com.br REVIEW ARTICLE ଝ Repercussions of inborn errors of immunity on growth a,b,∗ c,d e Ekaterini Simões Goudouris , Gesmar Rodrigues Silva Segundo , Cecilia Poli a Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Medicina, Departamento de Pediatria, Rio de Janeiro, RJ, Brazil b Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Curso de Especializac¸ão em Alergia e Imunologia Clínica, Rio de Janeiro, RJ, Brazil c Universidade Federal de Uberlândia (UFU), Faculdade de Medicina, Departamento de Pediatria, Uberlândia, MG, Brazil d Universidade Federal de Uberlândia (UFU), Hospital das Clínicas, Programa de Residência Médica em Alergia e Imunologia Pediátrica, Uberlândia, MG, Brazil e Universidad del Desarrollo,
  • Skeletal Dysplasias

    Skeletal Dysplasias

    Skeletal Dysplasias North Carolina Ultrasound Society Keisha L.B. Reddick, MD Wilmington Maternal Fetal Medicine Development of the Skeleton • 6 weeks – vertebrae • 7 weeks – skull • 8 wk – clavicle and mandible – Hyaline cartilage • Ossification – 7-12 wk – diaphysis appears – 12-16 wk metacarpals and metatarsals – 20+ wk pubis, calus, calcaneus • Visualization of epiphyseal ossification centers Epidemiology • Overall 9.1 per 1000 • Lethal 1.1 per 10,000 – Thanatophoric 1/40,000 – Osteogenesis Imperfecta 0.18 /10,000 – Campomelic 0.1 /0,000 – Achondrogenesis 0.1 /10,000 • Non-lethal – Achondroplasia 15 in 10,000 Most Common Skeletal Dysplasia • Thantophoric dysplasia 29% • Achondroplasia 15% • Osteogenesis imperfecta 14% • Achondrogenesis 9% • Campomelic dysplasia 2% Definition/Terms • Rhizomelia – proximal segment • Mezomelia –intermediate segment • Acromelia – distal segment • Micromelia – all segments • Campomelia – bowing of long bones • Preaxial – radial/thumb or tibial side • Postaxial – ulnar/little finger or fibular Long Bone Segments Counseling • Serial ultrasound • Genetic counseling • Genetic testing – Amniocentesis • Postnatal – Delivery center – Radiographs Assessment • Which segment is affected • Assessment of distal extremities • Any curvatures, fracture or clubbing noted • Are metaphyseal changes present • Hypoplastic or absent bones • Assessment of the spinal canal • Assessment of thorax. Skeletal Dysplasia Lethal Non-lethal • Thanatophoric • Achondroplasia • OI type II • OI type I, III, IV • Achondrogenesis • Hypochondroplasia
  • Genes in Eyecare Geneseyedoc 3 W.M

    Genes in Eyecare Geneseyedoc 3 W.M

    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
  • Larsen Syndrome

    Larsen Syndrome

    I M A G E S Larsen Syndrome Larsen syndrome (OMIM 150250) is a complex syndrome with genetic heterogeneity, and with both autosomal dominant and autosomal recessive An eleven year old male child born to a patterns of inheritance. Mutations in gene encoding nonconsanguinous couple presented with multiple filamin B (FLNB) result in Larsen syndrome. This joint dislocation since birth. He had mild motor gene has an important role in vertebral delay. Examination showed presence of short segmentation, joint formation and endochondral stature. There was no microcephaly. He had flat ossification and is also mutated in atelosteogenesis facies, prominent forehead, depressed nasal bridge, types I and III, and in spondylocarpotarsal and hypertelorism (Fig. 1). He had bilateral syndromes. Autosomal dominant form is rhizomelic shortening of upper limbs, spatulate and characterized by flat facies, joint hypermobility, dislocated thumbs (Fig. 2), bilateral elbow, ankle, congenital multiple joint dislocations, especially of and hip dislocation (Fig.3). Examination of parents the knees and talipes equinovarus. The mid-face is did not reveal any features of Larsen syndrome. hypoplastic with a depressed nasal bridge. Cleft X-rays of long bones showed presence of bilateral palate may be present. Osteoarthritis involving large tibio-femoral and patellar dislocation at knees and joints and progressive kyphoscoliosis are potential dislocation at hip, ankles and thumbs. He also had complications. Airway obstruction caused by hypoplastic fibula on right side. X-ray spine showed tracheomalacia and bronchomalacia may be life presence of short and thick pedicles, kyphosis and threatening. All affected individuals should be hypoplastic superior articular facets. There was no evaluated for cervical spine instability and caution atlanto axial dislocation.
  • Current Overview of Osteogenesis Imperfecta

    Current Overview of Osteogenesis Imperfecta

    medicina Review Current Overview of Osteogenesis Imperfecta Mari Deguchi *, Shunichiro Tsuji , Daisuke Katsura , Kyoko Kasahara, Fuminori Kimura and Takashi Murakami Department of Obstetrics & Gynecology, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan; [email protected] (S.T.); [email protected] (D.K.); [email protected] (K.K.); [email protected] (F.K.); [email protected] (T.M.) * Correspondence: [email protected] Abstract: Osteogenesis imperfecta (OI), or brittle bone disease, is a heterogeneous disorder charac- terised by bone fragility, multiple fractures, bone deformity, and short stature. OI is a heterogeneous disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. Severe OI is perinatally lethal, while mild OI can sometimes not be recognised until adulthood. Severe or lethal OI can usually be diagnosed using antenatal ultrasound and confirmed by various imaging modalities and genetic testing. The combination of imaging parameters obtained by ultrasound, computed tomography (CT), and magnetic resource imaging (MRI) can not only detect OI accurately but also predict lethality before birth. Moreover, genetic testing, either noninvasive or invasive, can further confirm the diagnosis prenatally. Early and precise diagnoses provide parents with more time to decide on reproductive options. The currently available postnatal treatments for OI are not curative, and individuals with severe OI suffer multiple fractures and bone deformities throughout their lives. In utero mesenchymal stem cell transplantation has been drawing attention as a promising therapy for severe OI, and a clinical trial to assess the safety and efficacy of cell therapy is currently ongoing.
  • Dwarfism Awareness

    Dwarfism Awareness

    LPA Mission Statement LPA is dedicated to improving the quality of life for people with dwarfism throughout their lives, while celebrating with great pride little people’s contribution to social diversity. LPA strives to bring solutions and global For More Information awareness to the prominent issues affecting individuals of Contact LPA short stature and their families. Toll Free…(888) LPA-2001 Direct....(714) 368-3689 Fax…..(707) 721-1896 Dwarfism Check out our website at Awareness www.lpaonline.org A Community Outreach Program 617 Broadway #518 Sponsored by Little People of America Sonoma, CA 95476 LPA is a non-profit tax exempt 501(c)3 organization funded by individual donations. Contact LPA to help. Dwarfism - Facts and Fiction Mythbusters Terminology Bodies come in all shapes and sizes. There are about 400 People with dwarfism are not magical; they do not fly, nor are Preferred terminology is a personal decision, but different types of dwarfism. Each type of dwarfism is they leprechauns, elves, fairies or any other mythological commonly accepted terms are - short stature, different than the other. Many types of dwarfism have creature. They are people - people whose bones happen to dwarfism, little person, dwarf. And we say some medical complications but most people have an grow differently than yours. That is all. "average-height" instead of "normal height". average lifespan, being productive members of society. People with dwarfism do not all know each People with dwarfism are different, yes, but not Eighty percent of people with dwarfism have average- other or look alike, nor are there towns "abnormal". height parents and siblings.
  • Craniosynostosis Genetics: the Mystery Unfolds

    Craniosynostosis Genetics: the Mystery Unfolds

    Review Article Craniosynostosis genetics: The mystery unfolds Inusha Panigrahi Department of Pediatrics, Genetic and Metabolic Unit, Advanced Pediatric Center, PGIMER, Chandigarh, India The syndromes associated with craniosynostosis Craniosynsostosis syndromes exhibit considerable phenotypic and genetic heterogeneity. Sagittal synostosis include Apert syndrome, Crouzon syndrome, Greig is common form of isolated craniosynostosis. The cephalopolysyndactyly, and Saethre-Chotzen syndrome. sutures involved, the shape of the skull and associated malformations give a clue to the specific diagnosis. It is genetically heterogeneous disorder with mutation Crouzon syndrome is one of the most common of the identifi ed in several genes, predominantly the fi broblast craniosynostosis syndromes. Apert syndrome accounts for growth factor receptor genes.[3,4] Saethre-Chotzen 4.5% of all craniosynostoses and is one of the most serious of these syndromes. Most syndromic craniosynostosis syndrome and craniosynostosis (Boston-type) arise require multidisciplinary management. The following review from mutations in the Twist and muscle segment provides a brief appraisal of the various genes involved in craniosynostosis syndromes, and an approach to diagnosis homeobox 2 (MSX2) transcription factors, respectively. and genetic counseling. Rates of neuropsychological defi cits range from 35 to Key words: Apert syndrome, FGFR2 mutations, 50% in school-aged children with isolated single suture hydrocephalus, plagiocephaly, sutural synostosis, craniosynostosis.[5] Secondary effects of craniosynostosis syndromes may include vision problems and increased intracranial pressure, among others. Patients with TWIST gene Introduction mutations may have more ophthalmic abnormalities, including more strabismus, ptosis, and amblyopia.[6] The following discussion gives a comprehensive review Craniosynostosis, premature suture fusion, is one of of different disorders presenting with craniosynostosis, the most common craniofacial anomalies with incidence their diagnosis, and genetic counseling.
  • Ultrasonic Demonstration of Fetal Skeletal Dysplasia Case Reports

    Ultrasonic Demonstration of Fetal Skeletal Dysplasia Case Reports

    222 SAMJ VOLUME 67 9 FEBRUARY 1985 Ultrasonic demonstration of fetal skeletal dysplasia Case reports L1NNIE M. MULLER, B. J. CREMIN Toshiba linear array scanners (with 3,5 mHz transducers) and a Philips SDU 7000 Sector/Static scanner. A routine obstetric Summary scan does not involve complete examination of all limbs, but Reports on prenatal diagnosis in cases of skeletal when a bony abnormality is noted a skeletal survey is dysplasia have mostly been in high-risk mothers attempted. Real-time ultrasound offers a flexible technique, with a suspect genetic background where the fetal and when the infant is in the prone vertex position the linear lesion could probably be predetermined. We deal array has the advantage of a wider range of skeletal visualiza­ with routine ultrasonographic appraisal of the fetal tion. skeleton when dysplasia is not initially suspected, A complete skeletal survey consists of an evaluation of the and relate our experience of the lethal forms of this bones of the skull, spine, thorax and limbs and of correlating these other fetal structures. We first measured the biparietal condition. During the 4-year period 1981 - 1984,6 cases of skeletal dysplasia, including thanatophoric diameter (BPD) and then noted the echogenic characteristics dysplasia, achondrogenesis, the Ellis-van Creveld of the skull and facial contours. A comprehensive evaluation of syndrome (chondro-ectodermal dysplasia) and the spine is possible from 17 weeks' gestation onwards. In a osteogenesis imperfecta, were detected; the ultra­ longitudinal plane the posterior elements form segmented sonographic findings are discussed. bands of echoes that conform to the fetal kyphosis, but it is not always possible to visualize the whole spine.
  • Blueprint Genetics Craniosynostosis Panel

    Blueprint Genetics Craniosynostosis Panel

    Craniosynostosis Panel Test code: MA2901 Is a 38 gene panel that includes assessment of non-coding variants. Is ideal for patients with craniosynostosis. About Craniosynostosis Craniosynostosis is defined as the premature fusion of one or more cranial sutures leading to secondary distortion of skull shape. It may result from a primary defect of ossification (primary craniosynostosis) or, more commonly, from a failure of brain growth (secondary craniosynostosis). Premature closure of the sutures (fibrous joints) causes the pressure inside of the head to increase and the skull or facial bones to change from a normal, symmetrical appearance resulting in skull deformities with a variable presentation. Craniosynostosis may occur in an isolated setting or as part of a syndrome with a variety of inheritance patterns and reccurrence risks. Craniosynostosis occurs in 1/2,200 live births. Availability 4 weeks Gene Set Description Genes in the Craniosynostosis Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ALPL Odontohypophosphatasia, Hypophosphatasia perinatal lethal, AD/AR 78 291 infantile, juvenile and adult forms ALX3 Frontonasal dysplasia type 1 AR 8 8 ALX4 Frontonasal dysplasia type 2, Parietal foramina AD/AR 15 24 BMP4 Microphthalmia, syndromic, Orofacial cleft AD 8 39 CDC45 Meier-Gorlin syndrome 7 AR 10 19 EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 12 66 EFNB1 Craniofrontonasal dysplasia XL 28 116 ERF Craniosynostosis 4 AD 17 16 ESCO2 SC phocomelia syndrome, Roberts syndrome
  • MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature

    MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature

    J M Wit and others Genetics of short stature 174:4 R145–R173 Review MECHANISMS IN ENDOCRINOLOGY Novel genetic causes of short stature 1 1 2 2 Jan M Wit , Wilma Oostdijk , Monique Losekoot , Hermine A van Duyvenvoorde , Correspondence Claudia A L Ruivenkamp2 and Sarina G Kant2 should be addressed to J M Wit Departments of 1Paediatrics and 2Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Email The Netherlands [email protected] Abstract The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature.
  • Orphanet Report Series Rare Diseases Collection

    Orphanet Report Series Rare Diseases Collection

    Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic