Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel Test code: MA4301 Is a 374 gene panel that includes assessment of non-coding variants. This panel covers the majority of the genes listed in the Nosology 2015 (PMID: 26394607) and all genes in our Malformation category that cause growth retardation, short stature or skeletal dysplasia and is therefore a powerful diagnostic tool. It is ideal for patients suspected to have a syndromic or an isolated growth disorder or a skeletal dysplasia. About Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders This panel covers a broad spectrum of diseases associated with growth retardation, short stature or skeletal dysplasia. Many of these conditions have overlapping features which can make clinical diagnosis a challenge. Genetic diagnostics is therefore the most efficient way to subtype the diseases and enable individualized treatment and management decisions. Moreover, detection of causative mutations establishes the mode of inheritance in the family which is essential for informed genetic counseling. For additional information regarding the conditions tested on this panel, please refer to the National Organization for Rare Disorders and / or GeneReviews. Availability 4 weeks Gene Set Description Genes in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders 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 ACTB* Baraitser-Winter syndrome AD 55 60 ACTG1* Deafness, Baraitser-Winter syndrome AD 27 47 ACVR1 Fibrodysplasia ossificans progressiva AD 14 19 ADAMTS10 Weill-Marchesani syndrome AR 8 14 ADAMTS17 Weill-Marchesani-like syndrome AR 6 7 ADAMTSL2*,# Geleophysic dysplasia 3 AR 8 28 AGPS Rhizomelic chondrodysplasia punctata type 3 AR 4 8 AIFM1 Deafness, Combined oxidative phosphorylation deficiency XL 27 31 6, Cowchock syndrome AKT1 Proteus syndrome, Cowden syndrome AD 5 6 https://blueprintgenetics.com/ ALPL Odontohypophosphatasia, Hypophosphatasia perinatal AD/AR 78 291 lethal, infantile, juvenile and adult forms ALX3 Frontonasal dysplasia type 1 AR 8 8 ALX4 Frontonasal dysplasia type 2, Parietal foramina AD/AR 15 24 AMER1 Osteopathia striata with cranial sclerosis XL 14 40 AMMECR1 Midface hypoplasia, hearing impairment, elliptocytosis, XL 4 5 and nephrocalcinosis ANKH Calcium pyrophosphate deposition disease (familial AD 13 20 chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type ANKRD11* KBG syndrome AD 142 132 ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 AD/AR 64 121 muscular dystrophies ARCN1 Rhizomelic short stature with microcephaly, micrognathia, AD 3 3 and developmental delay (SRMMD) ARHGAP31 Adams-Oliver syndrome AD 3 6 ARID1A Coffin-Siris syndrome, Mental retardation AD 27 35 ARID1B Coffin-Siris syndrome, Mental retardation AD 153 185 ARSB Mucopolysaccharidosis (Maroteaux-Lamy) AR 118 201 ARSE* Chondrodysplasia punctata X-linked recessive, XL 22 46 brachytelephalangic type (CDPX1) ATP6V0A2 Cutis laxa, Wrinkly skin syndrome AR 16 56 ATR Cutaneous telangiectasia and cancer syndrome, Seckel AD/AR 10 33 syndrome B3GALT6 Spondyloepimetaphyseal dysplasia with joint laxity, AR 17 27 Ehlers-Danlos syndrome B3GAT3* Multiple joint dislocations, short stature, craniofacial AR 6 13 dysmorphism, and congenital heart defects B4GALT7 Ehlers-Danlos syndrome, progeroid form AR 8 9 BCS1L Bjornstad syndrome, GRACILE syndrome, Leigh AR 42 37 syndrome, Mitochondrial complex III deficiency, nuclear type 1 BGN Spondyloepimetaphyseal dysplasia, X-linked, Meester- XL 8 7 Loeys syndrome BHLHA9 Syndactyly Malik-Percin type, mesoaxial synostotic, with AR 4 43 phalangeal reduction, Split hand-foot malformation with long bone deficiency (SHFLD3), Gollop-Wolfgang BMP1 Osteogenesis imperfecta AR 7 21 https://blueprintgenetics.com/ BMP2 Brachydactyly type A2 AD 5 28 BMPER Diaphanospondylodysostosis AR 6 19 BMPR1B Acromesomelic dysplasia, Demirhan, Brachydactyly AD/AR 12 23 C/Symphalangism-like pheno, Brachydactyly type A2, Pulmonary arterial hypertension (PAH) BRAF* LEOPARD syndrome, Noonan syndrome, AD 134 65 Cardiofaciocutaneous syndrome BRCA2 Fanconi anemia, Medulloblastoma, Glioma susceptibility, AD/AR 3369 2659 Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familial BRIP1 Fanconi anemia, Breast cancer AD/AR 238 189 CA2 Osteopetrosis, with renal tubular acidosis AR 9 31 CANT1 Desbuquois dysplasia AR 20 28 CASR Hypocalcemia, Neonatal hyperparathyroidism, Familial AD/AR 104 396 Hypocalciuric hypercalcemia with transient Neonatal hyperparathyroidism CBL Noonan syndrome-like disorder with or without juvenile AD 24 43 myelomonocytic leukemia CCDC47 Microcephaly, Malformations AR 1 CCDC8 Three M syndrome 3 AR 2 3 CDC42 Takenouchi-Kosaki syndrome, Noonan-syndrome like AD 11 9 phenotype CDC45 Meier-Gorlin syndrome 7 AR 10 19 CDC6 Meier-Gorlin syndrome (Ear-patella-short stature AR 2 2 syndrome) CDH11 AR 3 8 CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 35 81 CDT1 Meier-Gorlin syndrome (Ear-patella-short stature AR 6 12 syndrome) CENPJ Seckel syndrome, Microcephaly AR 34 9 CEP152# Seckel syndrome, Microcephaly AR 20 20 CEP63 Seckel syndrome AR 7 2 CHST14 Ehlers-Danlos syndrome, musculocontractural AR 15 21 CHST3 Spondyloepiphyseal dysplasia with congenital joint AR 18 37 dislocations (recessive Larsen syndrome) CHSY1 Temtamy preaxial brachydactyly syndrome AR 6 16 CKAP2L Filippi syndrome AR 7 7 https://blueprintgenetics.com/ CLCN5 Proteinuria, low molecular weight, with hypercalciuric XL 48 272 nephrocalcinosis, Hypophosphatemic rickets,, Nephrolithiasis, I, Dent disease 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 COL27A1 Steel syndrome AR 7 7 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 COL3A1 Ehlers-Danlos syndrome AD 520 631 COL5A1 Ehlers-Danlos syndrome AD 101 154 COL5A2 Ehlers-Danlos syndrome AD 24 35 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) COL9A3 Multiple epihyseal dysplasia type 3 (EDM3), Stickler AD/AR 10 14 syndrome recessive type COMP Pseudoachondroplasia, Multiple ephiphyseal dysplasia AD 43 186 CREB3L1 Osteogenesis imperfecta, type XVI AR 2 3 CREBBP Rubinstein-Taybi syndrome AD 175 362 CRLF1 Crisponi syndrome, Cold-induced sweating syndrome, AR 21 37 type 1 https://blueprintgenetics.com/ 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 DDR2 Spondylometaepiphyseal dysplasia, short limb-hand type AR 11 9 DHCR24 Desmosterolosis AR 6 9 DHCR7 Smith-Lemli-Opitz syndrome AR 88 217 DHODH Postaxial acrofacial dysostosis (Miller syndrome) AR 8 20 DLL3 Spondylocostal dysostosis AR 12 26 DLL4 Adams-Oliver syndrome AD 13 14 DLX3 Amelogenesis imperfecta, Trichodontoosseous syndrome AD 5 11 DLX5 Split-hand/foot malformation with sensorineural hearing AR 3 9 loss DMP1 Hypophosphatemic rickets AR 5 10 DOCK6 Adams-Oliver syndrome AR 21 21 DONSON Microcephaly, short stature, and limb abnormalities 10 19 (MISSLA), Microcephaly-Micromelia syndrome 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) EFNB1 Craniofrontonasal dysplasia XL 28 116 EFTUD2 Mandibulofacial dysostosis with microcephaly, Esophageal AD 45 99 atresia, syndromic EIF2AK3 SED, Wolcott-Rallison type AR 9 80 ENAM Amelogenesis imperfecta AD/AR 8 18 ENPP1 Arterial calcification, Hypophosphatemic rickets AD/AR 22 72 EOGT Adams-Oliver syndrome AR 8 5 https://blueprintgenetics.com/ EP300 Rubinstein-Taybi syndrome AD 63 101 ERCC4 Fanconi anemia, Xeroderma pigmentosum, XFE progeroid AR 13 70 syndrome ESCO2 SC phocomelia syndrome,