Klinische FragestellungNeuropathie, CMT2/HMSNII, axonal; Differentialdiagnose

NGS +

[[Sanger]]

Hereditäre motorische und sensorische Neuropathien (HMSN) oder Charcot-Marie-Tooth-(CMT) Erkrankungen und verwandte Neuropathien sind eine Gruppe von klinisch und genetisch heterogenen Leiden, die primär das periphere Nervensystem mit sekundärem Muskelschwund und Schwäche betreffen. CMT ist die häufigste vererbte neuromuskuläre Störung, und diese Patienten können sich mit vielen Symptomen präsentieren, wobei in allen Altersgruppen üblicherweise motorische Anzeichen gegenüber sensorischen Symptomen überwiegen. CMT kann im Säuglingsalter beginnen, in der Adoleszenz oder lebenslang mit milden Symptomen auftreten - selbst asymptomatische Verwandte können in bestimmten Familien nachgewiesen werden. Die motorischen Nervenleit-Geschwindigkeiten (NCV) unterscheiden zwei Haupttypen: CMT1 (demyelinisierend; NCV<35m/sec) und CMT2 (axonal; NCV>45m/sec). Die CMT-Neuropathie kann entweder autosomal dominant, rezessiv oder X-chromosomal (CMTX-Formen) vererbt werden und tritt häufig als sporadische Neuropathie auf. Bislang wurden über 60 verschiedene genetische Loci mit CMT1-4 und CMTdi (dominanter intermediärer Typ; NCV 35-45m/sec) in Verbindung gebracht. Fast alle der relevanten Gene sind identifiziert. Diese Gene kodieren für Proteine, die an der Myelinisierung, der Schwann-Zell-Differenzierung, dem axonalen Transport, dem endozytären Recycling, der mitochondrialen Funktion, der Protein-Translation, der Signaltransduktion, der Reparatur von Einzelstrang-DNA-Brüchen und anderen Prozessen beteiligt sind. Die bisher berichteten DNA-Diagnoseausbeuten für alle CMT-Formen unterscheiden sich erheblich von >20% bis >60%, wahrscheinlich in Abhängigkeit vom Grad der klinischen Aufarbeitung. Negative molekulargenetische Ergebnisse schließen die klinische Diagnose keinesfalls aus.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1358/

• Alias: CMT2, Charcot-Marie-Tooth type 2
• Alias: HMSNII
• Alias: Polyneuropathie
• Allelic: Amyotrophic lateral sclerosis, susceptibility to (NEFH)
• Allelic: Arts syndrome (PRPS1)
• Allelic: Ataxia-oculomotor apraxia 4 (PNKP)
• Allelic: Combined oxidative phosphorylation deficiency 6 (AIFM1)
• Allelic: Combined oxidative phosphorylation deficiency 7 (MTRFR)
• Allelic: Cortical dysplasia, complex, with other brain malformations 1 (TUBB3)
• Allelic: Deafness, AR 89 (KARS1)
• Allelic: Deafness, XL 1 (PRPS1)
• Allelic: Deafness, XL 5 (AIFM1)
• Allelic: Epileptic encephalopathy, early infantile, 29 (AARS)
• Allelic: Fibrosis of extraocular muscles, congenital, 3A (TUBB3)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Allelic: Glomerulosclerosis, focal segmental, 5 (INF2)
• Allelic: Gout, PRPS-related (PRPS1)
• Allelic: Hypomagnesemia, seizures + mental retardation 2 (ATP1A1)
• Allelic: Microcephaly, seizures, developmental delay (PNKP)
• Allelic: Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
• Allelic: Myoclonus, intractable, neonatal (KIF5A)
• Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
• Allelic: Myopia 6 (SCO2)
• Allelic: Pheochromocytoma (KIF1B)
• Allelic: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
• Allelic: Pontocerebellar hypoplasia, type 1E (SLC25A46)
• Allelic: Spastic ataxia, Charlevoix-Saguenay type (SACS)
• Allelic: Spastic paraplegia 10, AD (KIF5A)
• Allelic: Spastic paraplegia 55, AR (MTRFR)
• Allelic: Spastic paraplegia 57, AR (TFG)
• Allelic: Spinal muscular atrophy, distal, AR, 4 (PLEKHG5)
• Allelic: Spondyloepimetaphyseal dysplasia, XL, with hypomyelinating leukodystrophy (AIFM1)
• Allelic: Usher syndrome type 3B (HARS1)
• Basel-Vanagait-Smirin-Yosef syndrome (MED25)
• Charcot-Marie-Tooth disease, DI C (YARS1)
• Charcot-Marie-Tooth disease, DI D (MPZ)
• Charcot-Marie-Tooth disease, DI E (INF2)
• Charcot-Marie-Tooth disease, DI F (GNB4)
• Charcot-Marie-Tooth disease, DI G (NEFL)
• Charcot-Marie-Tooth disease, RI C (PLEKHG5)
• Charcot-Marie-Tooth disease, RI D (COX6A)
• Charcot-Marie-Tooth disease, RI, A (GDAP1)
• Charcot-Marie-Tooth disease, RI, B (KARS1)
• Charcot-Marie-Tooth disease, XLD, 6 (PDK3)
• Charcot-Marie-Tooth disease, XLI [OMIM: CMTX1] (DRP2)
• Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
• Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2CC (NEFH)
• Charcot-Marie-Tooth disease, axonal, type 2DD (ATP1A1)
• Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
• Charcot-Marie-Tooth disease, axonal, type 2F (HSPB1)
• Charcot-Marie-Tooth disease, axonal, type 2HH (JAG1)
• Charcot-Marie-Tooth disease, axonal, type 2K (GDAP1)
• Charcot-Marie-Tooth disease, axonal, type 2N (AARS)
• Charcot-Marie-Tooth disease, axonal, type 2W (HARS1)
• Charcot-Marie-Tooth disease, axonal, type 2Z (MORC2)
• Charcot-Marie-Tooth disease, axonal, with vocal cord paresis (GDAP1)
• Charcot-Marie-Tooth disease, type 1A (PMP22)
• Charcot-Marie-Tooth disease, type 1B (MPZ)
• Charcot-Marie-Tooth disease, type 1E (PMP22)
• Charcot-Marie-Tooth disease, type 1F (NEFL)
• Charcot-Marie-Tooth disease, type 2A1 (KIF1B)
• Charcot-Marie-Tooth disease, type 2A1 [OMIM] (DGAT2)
• Charcot-Marie-Tooth disease, type 2B2 (PNKP)
• Charcot-Marie-Tooth disease, type 2D (GARS1)
• Charcot-Marie-Tooth disease, type 2E (NEFL)
• Charcot-Marie-Tooth disease, type 2I (MPZ)
• Charcot-Marie-Tooth disease, type 2J (MPZ)
• Charcot-Marie-Tooth disease, type 4A (GDAP1)
• Charcot-Marie-Tooth neuropathy, XLD, 1 (GJB1)
• Cowchock syndrome (AIFM1)
• Dejerine-Sottas disease (MPZ, PMP22)
• Developmental delay, impaired growth, dysmorphic facies + axonal neuropathy (MORC2)
• Giant axonal neuropathy-1 (GAN)
• Giant axonal neuropathy-2, AD (DCAF8)
• Hereditary motor + sensory neuropathy VIA (MFN2)
• Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Hereditary motor and sensory neuropathy, Okinawa type (TFG)
• Hereditary neuropathies [panelapp] (KIF5A, TTR, TUBB3)
• Hereditary neuropathy [panelapp] (MTRFR)
• Hereditary neuropathy [panelapp] (SACS)
• Hereditary neuropathy [panelapp] (SCO2)
• Hypomyelinating neuropathy, congenital, 2 (MPZ)
• Infantile-onset multisystem neurologic, endocrine + pancreatic disease 2 (YARS1)
• Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
• Neuromyotonia and axonal neuropathy, AR (HINT1)
• Neuronopathy, distal hereditary motor, type IIB (HSPB1)
• Neuronopathy, distal hereditary motor, type VA (GARS1)
• Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Neuropathy, distal hereditary motor, type VA (BSCL2)
• Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
• Neuropathy, inflammatory demyelinating (PMP22)
• Neuropathy, recurrent, with pressure palsies (PMP22)
• Peripheral neuropathy, AR, with/-out impaired intellectual development (MCM3AP)
• Roussy-Levy syndrome (MPZ, PMP22)
• Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORD)
• Spinal muscular atrophy, Jokela type (CHCHD10)
• Spinal muscular atrophy, distal, AR, 5 (DNAJB2)