Klinische FragestellungSkelettdysplasie, Differentialdiagnose

NGS +

[Sanger]

Skelettdysplasien sind eine vielfältige Gruppe genetischer Erkrankungen des Skeletts, die sich gewöhnlich während des prä- und postnatalen Wachstums manifestieren. Es gibt über 450 verschiedene anerkannte Dysplasien. Sie führen zu einer Vielzahl von Phänotypen mit z.B. Kleinwüchsigkeit, Skelettdeformitäten und erhöhter Knochenbrüchigkeit. Jede einzelne Art von Skelettdysplasie ist selten, aber insgesamt liegt die Inzidenz weltweit bei etwa 1/5000-1/3000 Geburten. Skelettdysplasien sind genetisch heterogen und können als autosomal-dominante, autosomal-rezessive, X-chromosomal-rezessive und X-chromosomal-dominante Störungen vererbt werden. Seltenere genetische Krankheitsmechanismen wie chromosomale Deletionen/ Duplikationen, Keimbahnmosaike und uniparentale Disomie wurden ebenfalls beobachtet. Die DNA-diagnostische Ausbeute ist nicht genau bekannt. Daher bedeutet ein unauffälliger genetischer Befund keinen Ausschluss der klinischen Verdachtsdiagnose, insbesondere da die Differentialdiadiagnose mit (klinisch eng) verwandten Skelettdysplasien sehr schwierig sein kann.

Referenz: 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)