Klinische FragestellungArthrogrypose, syndromal; Differentialdiagnose

NGS +

Bei Arthrogrypose handelt es sich nicht um eine spezifische Diagnose, sondern um einen klinischen Befund, der ein Merkmal von mehreren hundert verschiedenen Erkrankungen sein kann. Definitionsgemäß sind mehrere angeborene Kontrakturen an mindestens zwei verschiedenen Stellen des Körpers betroffen. Distale Arthrogryposen stellen eine Untergruppe dieser Erkrankungen dar, die hauptsächlich die distalen Teile der Gliedmaßen betreffen. Sie sind durch angeborene Kontrakturen gekennzeichnet, in der Regel ohne eine primäre neurologische und/oder Muskelerkrankung. Zu den gemeinsamen Merkmalen aller distalen Arthrogryposen gehören ein einheitliches Muster der Beteiligung von Hand und Fuß, eine begrenzte Beteiligung der proximalen Gelenke und eine variable Expressivität. Zu den assoziierten Merkmalen der syndromalen Arthrogrypose gehören in abnehmender Häufigkeit eine Hirnbeteiligung (kognitive Beeinträchtigung, Epilepsie, Corpus-callosum-Agenesie, perisylvische Polymikrogyrie, Kleinhirnhypoplasie, Mikrozephalie, Makrozephalie, Ventrikulomegalie), intrauterine Wachstumsretardierung, Herzanomalien (Kardiomyopathie, kongenitale Herzfehler), Hämangiom im Gesicht, Nierenanomalien (uni-/bilaterale Pyelektasie, unilaterale Nierenagenesie, Nierenhypoplasie, Urolithiasis), Augenanomalien (Mikrophthalmus, Katarakt), Hörverlust, unilaterale Ohrhypoplasie, Anomalien der Nabelschnurarterie und Knochenagenesie. Amyoplasie ist eine eigenständige sporadische Form der Arthrogrypose mit charakteristischen klinischen Merkmalen, die in der Regel sporadisch auftritt. Die Vererbungsmuster für (syndromale) Arthrogryposen sind in der Regel autosomal rezessiv bzw. autosomal dominant, selten X-chromosomal. Da die diagnostische Ausbeute bei etwa 60% liegt, schließt ein negatives molekulargenetisches Ergebnis die klinische Diagnose nicht aus.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1379/

https://www.ncbi.nlm.nih.gov/books/NBK2594/

https://www.ncbi.nlm.nih.gov/books/NBK567492/

• Allelic: Alternating hemiplegia of childhood 1 (ATP1A2)
• Allelic: Barrett esophagus/esophageal adenocarcinoma (ASCC1)
• Allelic: CHAND syndrome (RIPK4)
• Allelic: Cardiac valvular dysplasia, XL (FLNA)
• Allelic: Cardiomyopathy, dilated, 1G (TTN)
• Allelic: Cardiomyopathy, dilated, 1S (MYH7)
• Allelic: Cardiomyopathy, dilated, 1X (FKTN)
• Allelic: Cardiomyopathy, familial hypertrophic, 26 (FLNC)
• Allelic: Cardiomyopathy, familial hypertrophic, 9 (TTN)
• Allelic: Cardiomyopathy, familial restrictive 5 (FLNC)
• Allelic: Cardiomyopathy, hypertrophic, 1 (MYH7)
• Allelic: Congenital short bowel syndrome (FLNA)
• Allelic: Developmental + epileptic encephalopathy 6B, non-Dravet (SCN1A)
• Allelic: Developmental + epileptic encephalopathy 98 (ATP1A2)
• Allelic: Dravet syndrome (SCN1A)
• Allelic: Dystonia 27 (COL6A3)
• Allelic: Dystonia-1, modifier of (TOR1A)
• Allelic: Dystonia-1, torsion (TOR1A)
• Allelic: Emery-Dreifuss muscular dystrophy 4, AD (SYNE1)
• Allelic: Erythroleukemia, familial, susceptibility to (ERBB3)
• Allelic: FG syndrome 2 (FLNA)
• Allelic: Febrile seizures, familial, 3A (SCN1A)
• Allelic: Focal segmental glomerulosclerosis 10 (LMX1B)
• Allelic: Generalized epilepsy with febrile seizures plus, type 2 (SCN1A)
• Allelic: Hardikar syndrome (MED12)
• Allelic: Heterotopia, periventricular, 1 (FLNA)
• Allelic: Immunodeficiency 9 (ORAI1)
• Allelic: Intestinal pseudoobstruction, neuronal (FLNA)
• Allelic: Larsen syndrome (FLNB)
• Allelic: Left ventricular noncompaction 5 (MYH7)
• Allelic: MEND syndrome (EBP)
• Allelic: Macular degeneration, early-onset (FBN2)
• Allelic: Malignant hyperthermia susceptibility 1 (RYR1)
• Allelic: Mandibuloacral dysplasia with type B lipodystrophy (ZMPSTE24)
• Allelic: Melnick-Needles syndrome (FLNA)
• Allelic: Mental retardation, AD 13 (DYNC1H1)
• Allelic: Migraine, familial basilar (ATP1A2)
• Allelic: Migraine, familial hemiplegic, 2 (ATP1A2)
• Allelic: Migraine, familial hemiplegic, 3 (SCN1A)
• Allelic: Myasthenic syndrome, cong., 3C, ass. with acetylcholine receptor deficiency (CHRND)
• Allelic: Myasthenic syndrome, congenital, 1A, slow-channel (CHRNA1)
• Allelic: Myasthenic syndrome, congenital, 1B, fast-channel (CHRNA1)
• Allelic: Myasthenic syndrome, congenital, 3A, slow-channel (CHRND)
• Allelic: Myasthenic syndrome, congenital, 3B, fast-channel (CHRND)
• Allelic: Myopathy, distal, 4 (FLNC)
• Allelic: Myopathy, myofibrillar, 5 (FLNC)
• Allelic: Orofacial cleft 6 (IRF6)
• Allelic: Osteogenesis imperfecta, type XI (FKBP10)
• Allelic: Polyglucosan body disease, adult form (GBE1)
• Allelic: Retinitis pigmentosa 76 (POMGNT1)
• Allelic: Sodium serum level QTL 1 (TRPV4)
• Allelic: Spastic paraplegia, intellectual disability, nystagmus, obesity (KIDINS220)
• Allelic: Spinocerebellar ataxia, AR 8 (SYNE1)
• Allelic: Spondylocarpotarsal synostosis syndrome (FLNB)
• Allelic: Visceral neuropathy, familial, 1, AR (ERBB3)
• Allelic: Xeroderma pigmentosum, group G (ERCC5)
• Allelic: Xeroderma pigmentosum, group G/Cockayne syndrome (ERCC5)
• Allelic: van der Woude syndrome (IRF6)
• Alkuraya-Kucinskas syndrome (KIAA1109 = BLTP1)
• Alkuraya-Kucinskas syndrome [arthrogryposis, brain abnormalities] (KIAA1109)
• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (POR)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect (LGI4)
• Arthrogryposis multiplex congenita 2, neurogenic type (ERGIC1)
• Arthrogryposis multiplex congenita 3, myogenic type (SYNE1)
• Arthrogryposis multiplex congenita 5 (TOR1A)
• Arthrogryposis multiplex congenita 6 (NEB)
• Arthrogryposis multiplex congenita [panelapp] (SCN1A)
• Arthrogryposis, Perthes disease, and upward gaze palsy (NEK9)
• Arthrogryposis, distal, type 2A, Freeman-Sheldon (MYH3)
• Arthrogryposis, distal, type 2B1 (TNNI2)
• Arthrogryposis, distal, type 2B2 (TNNT3)
• Arthrogryposis, distal, type 2B3, Sheldon-Hall (MYH3)
• Arthrogryposis, distal, type 5D (ECEL1)
• Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
• Arthrogryposis, renal dysfunction + cholestasis 2 (VIPAS39)
• Atelosteogenesis, type I (FLNB)
• Atelosteogenesis, type III (FLNB)
• Atelosteogenesis, types I, III; Boomerang dysplasia (FLNB)
• Avascular necrosis of femoral head, primary, 2 (TRPV4)
• Bethlem myopathy 1 (COL6A1-3)
• Bethlem myopathy 2 (COL12A1)
• Bohring-Opitz syndrome (ASXL1)
• Boomerang dysplasia (FLNB)
• Brachyolmia type 3 (TRPV4)
• Bruck syndrome 1 (FKBP10)
• Bruck syndrome 2 (PLOD2)
• CAP myopathy 1 (TPM3)
• CATSHL syndrome [CAmptodactyly, Tall Stature, Hearing Loss] (FGFR3)
• Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (PRG4)
• Carey-Fineman-Ziter syndrome [hypotonia, Moebius + Pierre Robin complex, delayed motor] (MYMK)
• Carney complex variant (MYH8)
• Central core disease (RYR1)
• Centronuclear myopathy 1 (DNM2)
• Cerebrooculofacioskeletal syndrome 3 (ERCC5)
• Charcot-Marie-Tooth disease, DI B (DNM2)
• Charcot-Marie-Tooth disease, axonal type 2M (DNM2)
• Charcot-Marie-Tooth disease, axonal, type 20 (DYNC1H1)
• Chondrodysplasia punctata, XLD (EBP)
• Cockayne syndrome, type A (ERCC8)
• Cockayne syndrome, type B (ERCC6)
• Cold-induced sweating syndrome 1 (CRLF1)
• Congenital arthrogryposis with anterior horn cell disease (GLE1)
• Congenital contractures of the limbs + face, hypotonia + developmental delay (NALCN)
• Congenital disorder of glycosylation, type Id (ALG3)
• Contractural arachnodactyly, congenital (FBN2)
• Contractures, pterygia, + spondylocarpostarsal fusion syndrome 1A (MYH3)
• Contractures, pterygia, + spondylocarpotarsal fusion syndrome 1B (MYh3)
• Desmosterolosis (DHCR24)
• Developmental + epileptic encephalopathy 69 (CACNA1E)
• Digital arthropathy-brachydactyly, familial (TRPV4)
• Distal arthrogryposis [panelapp] (ADAMTSL15)
• Distal myopathy + posterior leg + anterior hand involvement [MONDO:0013550] (FLNC)
• Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (PLOD1)
• Ehlers-Danlos syndrome, musculocontractural type 1 (CHST14)
• Escobar syndrome (CHRNG)
• Escobar syndrome [Lit.] (TPM2)
• Fetal akinesia deformation sequence 3 (DOK7)
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, dysmorphic facies (ATP1A2)
• Frontometaphyseal dysplasia 1 (FLNA)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Genitopatellar syndrome (KAT6B)
• Glycine encephalopathy with normal serum glycine (SLC6A9)
• Glycogen storage disease IV (GBE1)
• Glycogen storage disease VII (PFKM)
• Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Hyaline fibromatosis syndrome (ANTXR2)
• Hypomyelinating neuropathy, congenital, 3 (CNTNAP1)
• Hypotonia, infantile, with psychomotor retardation + characteristic facies 1 (NALCN)
• King-Denborough syndrome (RYR1)
• Laing distal myopathy (MYH7)
• Lethal congenital contractural syndrome 2 (ERBB3)
• Lethal congenital contracture syndrome 1 (GLE1)
• Lethal congenital contracture syndrome 10 (NEK9)
• Lethal congenital contracture syndrome 11 (GLDN)
• Lethal congenital contracture syndrome 5 (DNM2)
• Lethal congenital contracture syndrome 7 (CNTNAP1)
• Lethal congenital contracture syndrome 8 (ADCY6)
• Lethal congenital contracture syndrome 9 (ADGRG6)
• 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)
• Lujan-Fryns syndrome (MED12)
• Marden-Walker syndrome (PIEZO2)
• Metatropic dysplasia (TRPV4)
• Minicore myopathy with external ophthalmoplegia (RYR1)
• Multiple pterygium syndrome, lethal type (CHRNA1, CHRND, CHRNG)
• Muscular dystrophy, AR, with rigid spine + distal joint contractures (TOR1AIP)
• Muscular dystrophy, cong., merosin deficient or partially deficient (LAMA2)
• Muscular dystrophy, limb-girdle, AR 10 (TTN)
• Muscular dystrophy, limb-girdle, AR 23 (LAMA2)
• Muscular dystrophy, rigid spine, 1 (SELENON)
• Muscular dystrophy-dystroglycanopathy limb-girdle), type C, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy limb-girdle, type C, 7 (CRPPA)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies), type A, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies), type A, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies), type A, 6 (LARGE1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 10 (RXYLT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 11 (B3GALNT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 13 (B4GAT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 7 (CRPPA)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 8 (POMGNT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 9 (DAG1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation), type B, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation), type B, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation), type B, 6 (LARGE1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with/-out mental retardation, type B, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. without mental retardation, type B, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 9 (DAG1)
• Myasthenic syndrome, congenital, 10 (DOK7)
• Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (RAPSN)
• Myasthenic syndrome, congenital, 13, with tubular aggregates (DPAGT1)
• Myasthenic syndrome, congenital, 16 (SCN4A)
• Myasthenic syndrome, congenital, 20, presynaptic (SLC5A7)
• Myasthenic syndrome, congenital, 25 (VAMP1)
• Myasthenic syndrome, congenital, 2A, slow-channel (CHRNB1)
• Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency (CHRNB1)
• Myasthenic syndrome, congenital, 4A, slow-channel (CHRNE)
• Myasthenic syndrome, congenital, 4B, fast-channel (CHRNE)
• Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency (CHRNE)
• Myasthenic syndrome, congenital, 5 (COLQ)
• Myasthenic syndrome, congenital, 6, presynaptic (CHAT)
• Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency (MUSK)
• Myhre syndrome (SMAD4)
• Myopathy, actin, congenital, with cores (ACTA1)
• Myopathy, actin, congenital, with excess of thin myofilaments (ACTA1)
• Myopathy, congenital, Baily-Bloch (STAC3)
• Myopathy, congenital, with fast-twitch, type II, fiber atrophy (MYL1)
• Myopathy, congenital, with fiber-type disproportion (SELENON)
• Myopathy, congenital, with fiber-type disproportion (TPM3)
• Myopathy, congenital, with fiber-type disproportion 1 (ACTA1)
• Myopathy, myofibrillar, 9, with early respiratory failure (TTN)
• Myopathy, myosin storage, AD (MYH7)
• Myopathy, myosin storage, AR (MYH7)
• Myopathy, scapulohumeroperoneal (ACTA1)
• Myopathy, tubular aggregate, 2 (ORAI1)
• Myosclerosis, congenital (COL6A2)
• Myotubular myopathy, XL (MTM1)
• Nail-patella syndrome (LMX1B)
• Nemaline myopathy 1, AD/AR (TPM3)
• Nemaline myopathy 10 (LMOD3)
• Nemaline myopathy 2, AR (NEB)
• Nemaline myopathy 3, AR/AD (ACTA1)
• Nemaline myopathy 5, Amish type (TNNT1)
• Nemaline myopathy 8, AR (KLHL40)
• Nemaline myopathy 9 (KLHL41)
• Neurodevelopmental disorder with microcephaly, arthrogryposis + structural brain anomalies (SMPD4)
• Neuromuscular disease, congenital, with uniform type 1 fiber (RYR1)
• Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Ohdo syndrome, XL (MED12)
• Opitz-Kaveggia syndrome (MED12)
• Otopalatodigital syndrome, type I (FLNA)
• Otopalatodigital syndrome, type II (FLNA)
• PERCHING syndrome [global developm. delay, dysmorphic face, poor growth, contractures] (KLHL7)
• Parastremmatic dwarfism (TRPV4)
• Peroxisome biogenesis disorders (PEX1-3, PEX5-7, PEX10-14, PEX16, PEX19, PEX26)
• Pontocerebellar hypoplasia type 2A (TSEN54)
• Pontocerebellar hypoplasia type 4 (TSEN54)
• Pontocerebellar hypoplasia type 5 (TSEN54)
• Pontocerebellar hypoplasia, type 1B (EXOSC3)
• Popliteal pterygium syndrome 1 (IRF6)
• Popliteal pterygium syndrome, Bartsocas-Papas type (RIPK4)
• Proximal myopathy + ophthalmoplegia (MYBPC1)
• Proximal myopathy + ophthalmoplegia (MYH2)
• Raine syndrome [neonatal osteosclerotic bone dysplasia] (FAM20C)
• Restrictive dermopathy, lethal (ZMPSTE24)
• SED, Maroteaux type (TRPV4)
• Salih myopathy (TTN)
• Scapuloperoneal spinal muscular atrophy (TRPV4)
• Scapuloperoneal syndrome, myopathic type (MYH7)
• Schaaf-Yang syndr. [delayed psychomotor/intell. developm., hypotonia, behav. abnorm.] (MAGEL2)
• Schwartz-Jampel syndrome, type 1 (HSPG2)
• Shprintzen-Goldberg syndrome [craniosynostosis, marfanoid, skeletal, neurologic, cardiovasc.] (SKI)
• Spinal muscular atrophy with congenital bone fractures 2 (ASCC1)
• Spinal muscular atrophy, XL 2, infantile (UBA1)
• Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Spinal muscular atrophy, lower extremity-predominant, 2A, AD (BICD2)
• Spinal muscular atrophy, lower extremity-predominant, 2B, AD (BICD2)
• Spinal muscular atrophy-0, -1, -2, -3, -4 (SMN1)
• Spondylometaphyseal dysplasia, Kozlowski type (TRPV4)
• Stormorken syndrome [bleeding, thrombocytopenia, anemia, asplenia, tub. aggr. myopathy...] (STIM1)
• Terminal osseous dysplasia (FLNA)
• Tibial muscular dystrophy, tardive (TTN)
• Ullrich congenital muscular dystrophy 1 (COL6A1-3)
• Ullrich congenital muscular dystrophy 2 (COL12A1)
• Van den Ende-Gupta syndrome [contractual arachnodactyly + distinctive face] (SCARF2)
• Ventriculomegaly and arthrogryposis (KIDINS220)
• Weill-Marchesani syndrome 1, recessive (ADAMTS10)
• Wieacker-Wolff syndrome [severe neurodevelopmental disorder affecting CNS + PNS] (ZC4H2)