IllnessEhlers-Danlos syndromes, differential diagnosis

NGS +

[Sanger]

The different types of Ehlers-Danlos syndrome form a heterogeneous group of diseases characterised by fragility of the soft connective tissue and manifest themselves in the skin, ligaments, joints, blood vessels and/or internal organs. The clinical spectrum is very diverse and ranges from mild skin and joint hypermobility to severe physical disability and life-threatening vascular complications. An overlap with osteogenesis imperfecta is observed. Diseases in this group include classic Ehlers-Danlos syndrome (EDS), musculo-contractival EDS, hypermobile EDS, vascular EDS, arthrochalasia EDS, dermatosparax EDS, periodontal EDS, X-linked EDS, brittle corneal syndrome, classic type 1 and type 2 EDS, cardiac valve EDS, spondylodysplastic EDS, myopathic EDS and kyphoscoliotic EDS.

References: https://www.ncbi.nlm.nih.gov/books/NBK1244/

https://www.ncbi.nlm.nih.gov/books/NBK541503/

https://www.ncbi.nlm.nih.gov/books/NBK1462/

https://www.ncbi.nlm.nih.gov/books/NBK1494/

https://www.ncbi.nlm.nih.gov/books/NBK1279/

• Allelic: Aortic valve disease 1 (NOTCH1)
• Allelic: Developmental + epileptic encephalopathy 93 (ATP6V1A)
• Allelic: Leukemia, Philadelphia chromosome-positive, resistant to imatinib (ABL1)
• Allelic: Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (MYLK)
• Allelic: Mirror movements 1 and/or agenesis of the corpus callosum (DCC)
• Achondrogenesis, type II or hypochondrogenesis (COL2A1)
• Acromicric dysplasia (FBN1)
• Adams-Oliver syndrome 5 (NOTCH1)
• Al-Gazali syndrome (B3GALT6)
• Aortic aneurysm, familial thoracic 10 (LOX)
• Aortic aneurysm, familial thoracic 6 (ACTA2)
• Aortic aneurysm, familial thoracic 7 (MYLK)
• Arthrogryposis, distal, type 3 (PIEZO2)
• Arthrogryposis, distal, type 5 (PIEZO2)
• Arthrogryposis, distal, with impaired proprioception + touch (PIEZO2)
• Avascular necrosis of the femoral head (COL2A1)
• Bethlem myopathy 1 (COL6A1-3)
• Bethlem myopathy 2 (COL12A1)
• Bone mineral density variation QTL, osteoporosis (COL1A1)
• Brittle cornea syndrome 1 (ZNF469)
• Brittle cornea syndrome 2 (PTDM5)
• C1s deficiency (C1S)
• Caffey disease (COL1A1)
• Congenital heart defects + skeletal malformations syndrome (ABL1)
• Contractural arachnodactyly, congenital (FBN2)
• Cutis laxa, AD (ELN)
• Cutis laxa, AD 2 (FBLN5)
• Cutis laxa, AR, type IA (FBLN5)
• Cutis laxa, AR, type IB (EFEMP2)
• Cutis laxa, AR, type IIA (ATP6V0A2)
• Cutis laxa, AR, type IID (ATP6V1A)
• Cutis laxa, AR, type IIE (LTBP1)
• Cutis laxa, AR, type IIIA (ALDH18A1)
• Cutis laxa, autosomal recessive, type IC (LTBP4)
• Cutis laxa, autosomal recessive, type IIB-IIIB (PYCR1)
• Czech dysplasia (COL2A1)
• Ectopia lentis, familial (FBN1)
• Ehlers Danlos syndrome, musculocontractural type 1 (CHST14)
• Ehlers Danlos syndrome, type VI (PLOD1)
• Ehlers-Danlos syndrome due to tenascin X deficiency (TNXB)
• Ehlers-Danlos syndrome, arthrochalasia type, 1 (COL1A1)
• Ehlers-Danlos syndrome, arthrochalasia type, 2 (COL1A2)
• Ehlers-Danlos syndrome, cardiac valvular type (COL1A2)
• Ehlers-Danlos syndrome, classic type, 1 (COL5A1)
• Ehlers-Danlos syndrome, classic type, 2 (COL5A2)
• Ehlers-Danlos syndrome, classic-like, 2 (AEBP1)
• Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (PLOD1)
• Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (FKBP14)
• Ehlers-Danlos syndrome, musculocontractural type 2 (DSE))
• Ehlers-Danlos syndrome, periodontal type, 1 (C1R)
• Ehlers-Danlos syndrome, periodontal type, 2 (C1S)
• Ehlers-Danlos syndrome, spondylodysplastic type, 1 (B4GALT7)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (B3GALT6)
• Ehlers-Danlos syndrome, vascular type (COL3A1)
• Epiphyseal dysplasia, multiple, with myopia + deafness (COL2A1)
• Gaze palsy, familial horizontal, with progressive scoliosis, 1 (ROBO3)
• Gaze palsy, familial horizontal, with progressive scoliosis, 2 (DCC)
• Geleophysic dysplasia 2 (FBN1)
• Geroderma osteodysplasticum (GORAB)
• Homocystinuria, B6-responsive and nonresponsive types (CBS)
• Hypermobile Ehlers-Danlos syndrome (includes EDS type III)
• Kniest dysplasia (COL2A1)
• Kyphoscoliotic EDS (includes FKBP14-kEDS, PLOD1-kEDS)
• Legg-Calve-Perthes disease (COL2A1)
• Loeys-Dietz syndrome 1 (TGFBR1)
• Loeys-Dietz syndrome 2 (TGFBR2)
• Loeys-Dietz syndrome 3 (SMAD3)
• Loeys-Dietz syndrome 4 (TGFB2)
• Loeys-Dietz syndrome 5 (TGFB3)
• MASS syndrome (FBN1)
• Macrocephaly, alopecia, cutis laxa, scoliosis (RIN2)
• Macular degeneration, age-related, 3 (FBLN5)
• Macular degeneration, early-onset (FBN2)
• Marden-Walker syndrome (PIEZO2)
• Marfan lipodystrophy syndrome (FBN1)
• Marfan syndrome (FBN1)
• Meester-Loeys syndrome (BGN)
• Menkes disease (ATP7A)
• Moyamoya disease 5 (ACTA2)
• Multisystemic smooth muscle dysfunction syndrome (ACTA2)
• Neuropathy, hereditary, with or without age-related macular degeneration (FBLN5)
• Occipital horn syndrome (ATP7A)
• Osteoarthritis with mild chondrodysplasia (COL2A1)
• Osteogenesis imperfecta, type I-IV (COL1A1)
• Osteogenesis imperfecta, type II-IV (COL1A2)
• Platyspondylic skeletal dysplasia, Torrance type (COL2A1)
• Polymicrogyria with or without vascular-type EDS (COL3A1)
• Shprintzen-Goldberg syndrome (SKI)
• Spastic paraplegia 9A, AD (ALDH18A1)
• Spastic paraplegia 9B, AR (ALDH18A1)
• Spinal muscular atrophy, distal, X-linked 3 (ATP7A)
• Spondylocheirodysplasia, Ehlers-Danlos syndrome-like (SLC39A13)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with/-out fractures (B3GALT6)
• Spondyloepimetaphyseal dysplasia, Strudwick type (COL2A1)
• Spondyloepimetaphyseal dysplasia, X-linked (BGN)
• Spondyloepiphyseal dysplasia congenita (COL2A1)
• Spondyloepiphyseal dysplasia, Stanescu type (COL2A1)
• Spondyloperipheral dysplasia (COL2A1)
• Stickler sydrome, type I, nonsyndromic ocular (COL2A1)
• Stickler syndrome, type I (COL2A1)
• Stiff skin syndrome (FBN1)
• Supravalvar aortic stenosis (ELN)
• Thrombosis, hyperhomocysteinemic (CBS)
• Ullrich congenital muscular dystrophy 1 (COL6A1-3)
• Ullrich congenital muscular dystrophy 2 (COL12A1)
• VISS s.: Vascular aneurysm, immune dysregulation, skeletal anomalies, skin/joint laxity (IPO8)
• Vitreoretinopathy with phalangeal epiphyseal dysplasia (COL2A1)
• Weill-Marchesani syndrome 2, AD (FBN1)
• Wrinkly skin syndrome (ATP6V0A2)