IllnessSkeletal dysplasia, differential diagnosis

NGS +

[Sanger]

Skeletal dysplasias are a diverse group of genetic diseases of the skeleton that usually manifest during pre- and postnatal growth. There are over 450 different recognized dysplasias. They lead to a variety of phenotypes with e.g. dwarfism, skeletal deformities and increased bone fragility. Each individual type of skeletal dysplasia is rare, but the overall incidence worldwide is about 1/5000-1/3000 births. Skeletal dysplasias are genetically heterogeneous and can be inherited as autosomal dominant, autosomal recessive, X-linked recessive and X-linked dominant disorders. Rarer genetic disease mechanisms such as chromosomal deletions/duplications, germline mosaics and uniparental disomy have also been observed. The DNA diagnostic yield is not known exactly. Therefore, an inconspicuous genetic finding does not exclude a suspected clinical diagnosis, especially since differential diagnosis with (clinically closely) related skeletal dysplasias can be very difficult.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507692/

https://www.uptodate.com/contents/approach-to-prenatal-diagnosis-of-the-lethal-skeletal-dysplasias/print

• Alias: Skeletal dysplasia
• Allelic: Atrial fibrillation, familial, 12 (ABCC9)
• Allelic: Avascular necrosis of the femoral head (COL2A1)
• Allelic: Cardiomyopathy, dilated, 1O (ABCC9)
• Allelic: Deafness, AD 13 (COL11A2)
• Allelic: Deafness, AD 37 (COL11A1)
• Allelic: Deafness, AR 53 (COL11A2)
• Allelic: Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
• Allelic: Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Allelic: Intervertebral disc disease, susceptibility to (COL9A3)
• Allelic: Lumbar disc herniation, susceptibility to (COL11A1)
• Allelic: Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Allelic: Pelger-Huet anomaly (LBR)
• Allelic: Preterm premature rupture of the membranes, susceptibility to (SERPINH1)
• Allelic: Restrictive dermopathy, lethal (ZMPSTE24)
• Allelic: Reynolds syndrome (LBR)
• Allelic: Scapuloperoneal spinal muscular atrophy (TRPV4)
• Allelic: Short stature, idiopathic familial (SHOX)
• Allelic: Sodium serum level QTL 1 (TRPV4)
• Allelic: Stickler sydrome, type I, nonsyndromic ocular (COL2A1
• Acampomelic campomelic dysplasia (SOX9)
• Achondrogenesis Ib (SLC26A2)
• Achondrogenesis, type IA (TRIP11)
• Achondrogenesis, type II or hypochondrogenesis (COL2A1)
• Achondroplasia (FGFR3)
• Acromelic frontonasal dysostosis (ZSWIM6)
• Anauxetic dysplasia 1 (RMRP)
• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (POR)
• Atelosteogenesis, type II (SLC26A2)
• Avascular necrosis of femoral head, primary, 2 (TRPV4)
• Brachyolmia type 3 (TRPV4)
• Bruck syndrome 1 (FKBP10)
• Bruck syndrome 2 (PLOD2)
• CATSHL syndrome (FGFR3)
• Campomelic dysplasia (SOX9)
• Campomelic dysplasia with autosomal sex reversal (SOX9)
• Cartilage-hair hypoplasia (RMRP)
• Chondrodysplasia punctata, XLD (EBP)
• Chondrodysplasia punctata, XLR (ARSE)
• Chondrodysplasia punctata, XLR (ARSL)
• Cleidocranial dysplasia (RUNX2)
• Cleidocranial dysplasia, forme fruste, dental anomalies only (RUNX2)
• Cleidocranial dysplasia, forme fruste, with brachydactyly (RUNX2)
• Crouzon syndrome with acanthosis nigricans (FGFR3)
• Czech dysplasia (COL2A1)
• De la Chapelle dysplasia (SLC26A2)
• Diastrophic dysplasia (SLC26A2)
• Diastrophic dysplasia, broad bone-platyspondylic variant (SLC26A2)
• Digital arthropathy-brachydactyly, familial (TRPV4)
• Dyssegmental dysplasia, Silverman-Handmaker type (HSPG2)
• Epiphyseal dysplasia, multiple, 1 (COMP)
• Epiphyseal dysplasia, multiple, 2 (COL9A2)
• Epiphyseal dysplasia, multiple, 3, with/-out myopathy (COL9A3)
• Epiphyseal dysplasia, multiple, 4 (SLC26A2)
• Epiphyseal dysplasia, multiple, 6 (COL9A1)
• Epiphyseal dysplasia, multiple, with myopia + deafness (COL2A1)
• Fibrochondrogenesis 1 (COL11A1)
• Fibrochondrogenesis 2 (COL11A2)
• Hypertrichotic osteochondrodysplasia (ABCC9)
• Hypochondroplasia (FGFR3)
• Hypophosphatasia, adult, childhood, infantile (ALPL)
• Kniest dysplasia (COL2A1)
• LADD syndrome (FGFR3)
• Langer mesomelic dysplasia (SHOX)
• Legg-Calve-Perthes disease (COL2A1)
• Leri-Weill dyschondrosteosis (SHOX)
• MEND syndrome (EBP)
• Mandibuloacral dysplasia with type B lipodystrophy (ZMPSTE24)
• Marshall syndrome (COL11A1)
• Metaphyseal dysplasia with maxillary hypoplasia +/- brachydactyly (RUNX2)
• Metaphyseal dysplasia with maxillary hypoplasia with/-out brachydactyly (RUNX2)
• Metaphyseal dysplasia without hypotrichosis (RMRP)
• Metatropic dysplasia (TRPV4)
• Muenke syndrome (FGFR3)
• Neurodevelopmental disorder with movement abnormalities, abnormal gait + autistic features (ZSWIM6)
• Odontochondrodysplasia 1 (TRIP11)
• Odontohypophosphatasia (ALPL)
• Osteoarthritis with mild chondrodysplasia ((COL2A1)
• Osteogenesis imperfecta, type II (COL1A1, COL1A2)
• Osteogenesis imperfecta, type III (COL1A1, COL1A2)
• Osteogenesis imperfecta, type IV (COL1A1, COL1A2)
• Osteogenesis imperfecta, type IX (PPIB)
• Osteogenesis imperfecta, type V (IFITM5)
• Osteogenesis imperfecta, type VI (SERPINF1)
• Osteogenesis imperfecta, type VII (CRTAB)
• Osteogenesis imperfecta, type VIII (P3H1)
• Osteogenesis imperfecta, type X (SERPINH1)
• Osteogenesis imperfecta, type XI (FKBP10)
• Osteogenesis imperfecta, type XII (SP7)
• Osteogenesis imperfecta, type XIII (BMP1)
• Osteogenesis imperfecta, type XIV (TMEM38B)
• Osteogenesis imperfecta, type XV (WNT1)
• Osteogenesis imperfecta, type XVI (CREB3L1)
• Osteogenesis imperfecta, type XX (MESD)
• Otospondylomegaepiphyseal dysplasia, AD (COL11A2)
• Otospondylomegaepiphyseal dysplasia, AR (COL11A2)
• Parastremmatic dwarfism (TRPV4)
• Pelger-Huet anomaly with mild skeletal anomalies (LBR)
• Platyspondylic skeletal dysplasia, Torrance type (COL2A1)
• Progressive pseudorheumatoid dysplasia (CCN6)
• Pseudoachondroplasia (COMP)
• Rhizomelic chondrodysplasia punctata, type 2 (GNPAT)
• SADDAN (FGFR3)
• SED congenita (COL2A1)
• SED, Maroteaux type (TRPV4)
• SMED Strudwick type (COL2A1)
• Schimke immunoosseous dysplasia (SMARCAL1)
• Schneckenbecken dysplasia (SLC35D1)
• Schwartz-Jampel syndrome, type 1 (HSPG2)
• Short stature, advanced bone age, +- early-onset osteoarthritis +/- osteochondritis dissecans (ACAN)
• Short-rib thoracic dysplasia 11 with/-out polydactyly (DYNC2I2)
• Spondylocostal dysostosis 1, AR (DLL3)
• Spondyloenchondrodysplasia with immune dysregulation (ACP5)
• Spondyloepimetaphyseal dysplasia, aggrecan type (ACAN)
• Spondyloepiphyseal dysplasia tarda (TRAPPC2)
• Spondyloepiphyseal dysplasia, Kimberley type (ACAN)
• Spondyloepiphyseal dysplasia, Stanescu type (COL2A1)
• Spondylometaphyseal dysplasia, Kozlowski type (TRPV4)
• Spondyloperipheral dysplasia (COL2A1)
• Stickler syndrome, type I (COL2A1)
• Stickler syndrome, type II (COL11A1)
• Stickler syndrome, type IV (COL9A1)
• Stickler syndrome, type V (COL9A2)
• Thanatophoric dysplasia, type I (FGFR3)
• Thanatophoric dysplasia, type II (FGFR3)
• Vitreoretinopathy with phalangeal epiphyseal dysplasia (COL2A1)