Klinische FragestellungMuskeldystrophie, kongenital; erweiterte Differentialdiagnose
Zusammenfassung
Umfassendes differentialdiagnostisches panel für Muskeldystrophie, kongenitale, erweitert, mit 18 Leitlinien-kuratierten und insgesamt 72 kuratierten Genen gemäß klinischer Verdachtsdiagnose
171,3 kb (Erweitertes Panel: inkl. additional genes)
- EDTA-Blut (3-5 ml)
NGS +
Genpanel
Ausgewählte Gene
Name | Exon-Länge (bp) | OMIM-G | Referenz-Seq. | Erbgang |
---|---|---|---|---|
B3GALNT2 | 1503 | NM_152490.5 | AR | |
B4GAT1 | 1248 | NM_006876.3 | AR | |
COL6A1 | 3087 | NM_001848.3 | AD, AR | |
COL6A2 | 3060 | NM_001849.4 | AD, AR | |
COL6A3 | 9534 | NM_004369.4 | AD, AR | |
CRPPA | 1356 | NM_001101426.4 | AR | |
DAG1 | 2688 | NM_004393.6 | AR | |
FKRP | 1488 | NM_024301.5 | AR | |
FKTN | 1386 | NM_001079802.2 | AR | |
GMPPB | 1164 | NM_013334.4 | AR | |
LAMA2 | 9369 | NM_000426.4 | AR | |
LARGE1 | 2271 | NM_004737.7 | AR | |
LMNA | 1995 | NM_170707.4 | AD | |
POMGNT1 | 1983 | NM_017739.4 | AR | |
POMK | 1053 | NM_032237.5 | AR | |
POMT1 | 2244 | NM_007171.4 | AR | |
POMT2 | 2253 | NM_013382.7 | AR | |
SELENON | 1773 | NM_020451.3 | AR | |
ACTA1 | 1134 | NM_001100.4 | AD, AR | |
BIN1 | 1782 | NM_139343.3 | AR | |
CCDC78 | 1317 | NM_001031737.3 | AD | |
CFL2 | 501 | NM_021914.8 | AR | |
CHAT | 2247 | NM_020549.5 | AR | |
CHRNE | 1482 | NM_000080.4 | AD, AR | |
COL12A1 | 9192 | NM_004370.6 | AD, AR | |
COLQ | 1368 | NM_005677.4 | AR | |
DMD | 11058 | NM_004006.3 | XLR | |
DMPK | 1920 | NM_001081563.2 | AD | |
DNM2 | 2613 | NM_001005360.3 | AD | |
DOK7 | 1515 | NM_173660.5 | AR | |
DOLK | 1617 | NM_014908.4 | AR | |
DYSF | 6243 | NM_003494.4 | AR | |
GFPT1 | 2046 | NM_001244710.2 | AR | |
KBTBD13 | 1377 | NM_001101362.3 | AD | |
KLHL40 | 1866 | NM_152393.4 | AR | |
KLHL41 | 1821 | NM_006063.3 | AR | |
LMOD3 | 1683 | NM_198271.5 | AR | |
MAP3K20 | 2804 | NM_016653.3 | AR | |
MSTO1 | 1953 | NM_001256532.1 | AD, AR | |
MTM1 | 1812 | NM_000252.3 | XLR | |
MTMR14 | 1617 | NM_022485.5 | AD | |
POMGNT2 | 1743 | NM_032806.6 | AR | |
RAPSN | 1239 | NM_005055.5 | AR | |
RXYLT1 | 1355 | NM_014254.3 | AR | |
RYR1 | 15117 | NM_000540.3 | AD, AR | |
SIL1 | 1386 | NM_022464.5 | AR | |
SMN1 | 885 | NM_000344.4 | AR | |
SPEG | 9804 | NM_005876.5 | AR | |
SYNE1 | 26250 | NM_033071.4 | AD, AR | |
TCAP | 504 | NM_003673.4 | AR | |
TNNT1 | 837 | NM_003283.6 | AR | |
TPM2 | 855 | NM_003289.4 | AD | |
TPM3 | 858 | NM_152263.4 | AD, AR |
Infos zur Erkrankung
Kongenitale Muskeldystrophien (CMD) sind definiert als früh einsetzende Muskelerkrankungen, bei denen die Muskelbiopsie mit dem Vorhandensein eines dystrophischen Prozesses vereinbar ist, ohne dass histologische Hinweise auf eine andere neuromuskuläre Erkrankung vorliegen. Dennoch gibt es Überschneidungen zwischen CMDs und kongenitalen Myopathien auf klinischer, morphologischer und genetischer Ebene. Mutationen in mehreren Genen können sowohl kongenitale Myopathien als auch CMD-ähnliche Leiden verursachen. Myopathien spiegeln eine Pathologie wider, bei der es in den meisten Fällen keine eindeutigen Hinweise auf Degeneration und Regeneration gibt. Die klinische und genetische Komplexität der unter den CMD subsumierten Erkrankungen hat zu unterschiedlichen genetischen und klinischen Klassifizierungsschemata geführt. Die Inzidenz und Prävalenz von CMD in verschiedenen Populationen liegt zwischen 7-25/100 000. In Japan ist der am häufigsten diagnostizierte CMD-Subtyp die Fukuyama CMD, während Fukutin-Mutationen in anderen Populationen sehr selten sind. Einzelne CMD-Formen sind selten. Die molekulare Diagnose ist wichtig für die genetische Beratung, die Prognose und die vorausschauende Behandlung dieser heterogenen Erkrankungen, die derzeit unter CMD zusammengefasst werden, um z.B. spinale Muskelatrophie, Dysferlinopathie, Kollagen-VI-verwandte Dystrophien, LAMA2-Muskeldystrophie, Emery-Dreifuss-Muskeldystrophie, kongenitale Fukuyama-Muskeldystrophie usw. zu unterscheiden. Neben 17 Leitlinien-kuratierten CMD-Genen gehören zu den wichtigsten differentialdiagnostischen Überlegungen bei hypotonen und schwachen Säuglingen die kongenitalen Myopathien und die kongenitalen myasthenischen Syndrome. Die verschiedenen CMDs werden gemäß den unterschiedlichen monogenen Mustern vererbt. Die molekulargenetische diagnostische Gesamtausbeute ist nicht genauer bekannt, liegt sicherlich bei wenig mehr als 20%, so dass ein negatives DNA-Testergebnis die klinische Diagnose keineswegs ausschließt.
Ausgewählte Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1168/
https://www.ncbi.nlm.nih.gov/books/NBK1206/
https://www.ncbi.nlm.nih.gov/books/NBK1303/
https://www.ncbi.nlm.nih.gov/books/NBK1352/
https://www.ncbi.nlm.nih.gov/books/NBK1436/
https://www.ncbi.nlm.nih.gov/books/NBK1503/
https://www.ncbi.nlm.nih.gov/books/NBK97333/
- Alias: Congenital muscular dystrophy due to laminin alpha2 deficiency (LAMA2)
- Alias: Congenital muscular dystrophy type 1A (LAMA2)
- Alias: Laminin subunit alpha 2-related congenital muscular dystrophy (LAMA2)
- Alias: Merosin-negative congenital muscular dystrophy (LAMA2)
- Alias: Muskeldystrophie, kongenitale, Merosin-negativ (LAMA2)
- Alias: Muskeldystrophie, kongenitale, durch Laminin-alpha 2-Mangel (LAMA2)
- Alias: Santavuori congenital muscular dystrophy (POMGNT1)
- Alias: Walker-Warburg syndrome (POMT1)
- Allelic: Becker muscular dystrophy (DMD)
- Allelic: Cardiomyopathy, dilated, 1A (LMNA)
- Allelic: Cardiomyopathy, dilated, 1X (FKTN)
- Allelic: Cardiomyopathy, dilated, 3B (DMD)
- Allelic: Charcot-Marie-Tooth disease, axonal type 2M (DNM2)
- Allelic: Charcot-Marie-Tooth disease, dominant intermediate B (DNM2)
- Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
- Allelic: Dystonia 27 (COL6A3)
- Allelic: Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
- Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
- Allelic: Emery-Dreifuss muscular dystrophy 6, XL (FHL1)
- Allelic: Epidermolysis bullosa simplex 5A, Ogna type (PLEC)
- Allelic: Epidermolysis bullosa simplex 5C, with pyloric atresia (PLEC)
- Allelic: Epidermolysis bullosa simplex 5D, generalized intermediate, AR (PLEC)
- Allelic: Heart-hand syndrome, Slovenian type (LMNA)
- Allelic: Hutchinson-Gilford progeria (LMNA)
- Allelic: King-Denborough syndrome (RYR1)
- Allelic: Lipodystrophy, familial partial, type 2 (LMNA)
- Allelic: Malignant hyperthermia susceptibility 1 (RYR1)
- Allelic: Malouf syndrome (LMNA)
- Allelic: Mandibuloacral dysplasia (LMNA)
- Allelic: Minicore myopathy with external ophthalmoplegia (RYR1)
- Allelic: Muscular dystrophy, limb-girdle, AR 23 (LAMA2)
- Allelic: Muscular dystrophy, rigid spine, 1 (SELENON)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 1 (POMT1)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 14 (GMPPB)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 2 (POMT2)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 3 (POMGNT1)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 4 (FKTN)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 5 (FKRP)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 7 (CRPPA)
- Allelic: Muscular dystrophy-dystroglycanopathy [limb-girdle], type C, 9 (DAG1)
- Allelic: Myopathy, scapulohumeroperoneal (ACTA1)
- Allelic: Myosclerosis, congenital (COL6A2)
- Allelic: Reducing body myopathy, XL 1b, with late childhood or adult onset (FHL1)
- Allelic: Restrictive dermopathy, lethal (LMNA)
- Allelic: Retinitis pigmentosa 76 (POMGNT1)
- Allelic: Scapuloperoneal myopathy, XLD (FHL1)
- Allelic: Spinocerebellar ataxia, AR 8 (SYNE1)
- Allelic: Split-foot malformation with mesoaxial polydactyly (MAP3K20)
- Allelic:Emery-Dreifuss muscular dystrophy 4, AD (SYNE1)
- Arthrogryposis multiplex congenita 3, myogenic type (SYNE1)
- Arthrogryposis multiplex congenita 6 (NEB)
- Arthrogryposis, distal, type 1A + 2B4 (TPM2)
- Bethlem myopathy 1 (COL6A1, COL6A2, COL6A3)
- Bethlem myopathy 2 (COL12A1)
- CAP myopathy 1 (TPM3)
- CAP myopathy 2 (TPM2)
- Carey-Fineman-Ziter syndrome [cong. myopathy +Moebius- + Robin sequences] (MYMK)
- Central core disease (RYR1)
- Centronuclear myopathy 1 (DNM2)
- Centronuclear myopathy 2 (BIN1)
- Centronuclear myopathy 4 (CCDC78)
- Centronuclear myopathy 5 (SPEG)
- Centronuclear myopathy 6 with fiber-type disproportion (MAP3K20)
- Centronuclear myopathy, autosomal, modifier of (MTMR14)
- Congenital disorder of glycosylation, type Im (DOLK)
- Congenital disorder of glycosylation, type Iu (DPM2)
- Duchenne muscular dystrophy (DMD)
- Epidermolysis bullosa simplex 5B, with muscular dystrophy (PLEC)
- Fetal akinesia deformation sequence 2 (RAPSN)
- Fetal akinesia deformation sequence 3 (DOK7)
- Kollagen-VI-Muskeldystrophie (COL12A1)
- Lethal congenital contracture syndrome 5 (DNM2)
- Marinesco-Sjogren syndrome [cong. cataracts, myopathy, hypotonia, ID, hyperg. hypogonadism] (SIL1)
- Muscular dystrophy, congenital (LMNA)
- Muscular dystrophy, congenital, due to ITGA7 deficiency (ITGA7)
- Muscular dystrophy, congenital, megaconial type (CHKB)
- Muscular dystrophy, congenital, merosin deficient or partially deficient (LAMA2)
- Muscular dystrophy, congenital, with cataracts + intellectual disability (INPP5K)
- Muscular dystrophy, limb-girdle, AR 17 (PLEC)
- Muscular dystrophy, limb-girdle, AR 18 (TRAPPC11)
- Muscular dystrophy, rigid spine, 1 (SELENON)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies, type A, 10 (RXYLT1)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies], type A, 1 (POMT1)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies], type A, 11 (B3GALNT2)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies], type A, 13 (B4GAT1)
- 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, 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, 6 (LARGE1)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies], type A, 7 (CRPPA)
- Muscular dystrophy-dystroglycanopathy [cong. with brain + eye anomalies], type A, 9 (DAG1)
- Muscular dystrophy-dystroglycanopathy [cong. with mental retard.], type B, 1 (POMT1)
- Muscular dystrophy-dystroglycanopathy [cong. with mental retard.], type B, 2 (POMT2)
- Muscular dystrophy-dystroglycanopathy [cong. with mental retard.], type B, 3 (POMGNT1)
- Muscular dystrophy-dystroglycanopathy [cong. with mental retard.], type B, 6 (LARGE1)
- Muscular dystrophy-dystroglycanopathy [cong. with mental retardation], type B, 14 (GMPPB)
- Muscular dystrophy-dystroglycanopathy [cong. with/-out mental retard.], type B, 5 (FKRP)
- Muscular dystrophy-dystroglycanopathy [cong. without mental retard.], type B, 4 (FKTN)
- Myasthenia, congenital, 12, with tubular aggregates (GFPT1)
- Myasthenic syndrome, congenital, 10 ((DOK7)
- Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (RAPSN)
- 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)
- Myopathy with extrapyramidal signs (MICU1)
- Myopathy, XL, with postural muscle atrophy (FHL1)
- Myopathy, actin, congenital, with cores (ACTA1)
- Myopathy, actin, congenital, with excess of thin myofilaments (ACTA1)
- Myopathy, congenital, with fiber-type disproportion (SELENON)
- Myopathy, congenital, with fiber-type disproportion (TPM3)
- Myopathy, congenital, with fiber-type disproportion 1 (ACTA1)
- Myopathy, mitochondrial, + ataxia (MSTO1)
- Myotonic dystrophy 1 (DMPK_CTG)
- Myotubular myopathy, XL (MTM1)
- Nemaline myopathy 1, AD/AR (TPM3)
- Nemaline myopathy 10 (LMOD3)
- Nemaline myopathy 2, AR (NEB)
- Nemaline myopathy 3, AD/AR (ACTA1)
- Nemaline myopathy 4, AD (TPM2)
- Nemaline myopathy 5, Amish type (TNNT1)
- Nemaline myopathy 6, AD (KBTBD13)
- Nemaline myopathy 7, AR (CFL2)
- Nemaline myopathy 8, AR (KLHL40)
- Neuromuscular disease, congenital, with uniform type 1 fiber (RYR1)
- Reducing body myopathy, XL 1a, severe, infantile or early childhood onset (FHL1)
- Spinal muscular atrophy-1, -2, -3, -4 (SMN1)
- Ullrich congenital muscular dystrophy 1 (COL6A1, COL6A2, COL6A3)
- Ullrich congenital muscular dystrophy 2 (COL12A1)
- Uruguay faciocardiomusculoskeletal syndrome (FHL1)
- AD
- AR
- XLR
- Multiple OMIM-Ps
Bioinformatik und klinische Interpretation
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