Klinische FragestellungNeuropathie, CMT/HMSN, infantil/juvenil; autosomal dominant/X-gebunden; Differentialdiagnose

NGS +

Die klassische hereditäre motorisch-sensorische Neuropathie (HMSN/CMT) besteht in symmetrischer Schwäche (später Atrophie) der distalen Beinmuskeln und Abschwächung der Muskeleigenreflexe. Distale Sensibilitätsstörungen sind meist wenig ausgeprägt, die Krankheit verläuft variabel. Oft treten in den ersten zwei Jahrzehnten Fußfehlstellungen und Fußheberschwäche auf, selten Schmerzen in den Waden, im Verlauf ggf. auch ein neurogener Hohlfuß. Später sind auch die Hand- und Oberschenkelmuskulatur betroffen. Am häufigsten liegt eine demyelinisierende Form (HMSNI/CMT1) vor, worauf elektrophysiologisch die reduzierte motorische Nervenleitgeschwindigkeit (<38 m/sec) hinweist. Die axonale Variante der HMSN (HMSNII/CMT2) ist klinisch von der demyelinisierenden kaum zu unterscheiden, Übergänge und Mischformen erschweren die Zuordnung. Ähnliches gilt auch für die X-chromosomal dominante Variante (CMTX). Zusätzliche Symptome wie Hörstörungen, Optikusatrophie, auffallend rasche Progredienz, Skoliose, Niereninsuffizienz, mentale Retardierung oder Dysmorphien finden sich bei seltenen CMT-Formen. Wiewohl immer mehr Gene auch für seltenste CMT-Formen definiert werden, schließt ein unauffälliger genetischer Befund die klinische Verdachtsdiagnose nicht sicher aus.

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

• Alias: Charcot-Marie-Tooth [CMT] hereditary neuropathy
• Alias: HMSN
• Allelic: Amyloidosis, hereditary, transthyretin-related (TTR)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to (NEFH)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to, 25 (KIF5A)
• Allelic: Arts syndrome (PRPS1)
• Allelic: Carpal tunnel syndrome, familial (TTR)
• Allelic: Centronuclear myopathy 1 (DNM2)
• Allelic: Combined oxidative phosphorylation deficiency 6 (AIFM1)
• Allelic: Cortical dysplasia, complex, with other brain malformations 1 (TUBB3)
• Allelic: Cutis laxa, AD 2 (FBLN5)
• Allelic: Cutis laxa, AR, type IA (FBLN5)
• Allelic: Deafness, XL 1 (PRPS1)
• Allelic: Deafness, XL 5 (AIFM1)
• Allelic: Dejerine-Sottas disease (MPZ, PMP22)
• Allelic: Dystransthyretinemic hyperthyroxinemia (TTR)
• Allelic: Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• Allelic: Epileptic encephalopathy, early infantile, 29 (AARS1)
• Allelic: Fibrosis of extraocular muscles, congenital, 3A (TUBB3)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (VCP)
• Allelic: Glomerulosclerosis, focal segmental, 5 (INF2)
• Allelic: Gout, PRPS-related (PRPS1)
• Allelic: Hypomagnesemia, seizures + mental retardation 2 (ATP1A1)
• Allelic: Hypomyelinating neuropathy, congenital, 2 (MPZ)
• Allelic: Inclusion body myopathy with early-onset Paget disease + frontotemporal dementia 1 (VCP)
• Allelic: Interstitial lung + liver disease (MARS1)
• Allelic: Lethal congenital contracture syndrome 5 (DNM2)
• Allelic: Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Allelic: Macular degeneration, age-related, 3 (FBLN5)
• Allelic: Mental retardation, AD 13 (DYNC1H1)
• Allelic: Myoclonus, intractable, neonatal (KIF5A)
• Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
• Allelic: Neuroblastoma, susceptibility to, 1 (KIF1B)
• Allelic: Neuronopathy, distal hereditary motor, type IIA (HSPB8)
• Allelic: Neuronopathy, distal hereditary motor, type IIB (HSPB1)
• Allelic: Neuronopathy, distal hereditary motor, type VA (GARS1)
• Allelic: Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Allelic: Neuropathy, inflammatory demyelinating (PMP22)
• Allelic: Neuropathy, recurrent, with pressure palsies (PMP22)
• Allelic: Occipital horn syndrome (ATP7A)
• Allelic: Pheochromocytoma (KIF1B)
• Allelic: Roussy-Levy syndrome (MPZ, PMP22)
• Allelic: Silver spastic paraplegia syndrome (BSCL2)
• Allelic: Spastic paraplegia 10, AD (KIF5A)
• Allelic: Spastic paraplegia 57, AR (TFG)
• Allelic: Spinal muscular atrophy, distal, XL 3 (ATP7A)
• Allelic: Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Allelic: Spinocerebellar ataxia 43 (MME)
• Allelic: Spondyloepimetaphyseal dysplasia, XL, with hypomyelinating leukodystrophy (AIFM1)
• Allelic: Trichothiodystrophy 9, nonphotosensitive (MARS1)
• Allelic: Usher syndrome type 3B (HARS1)
• Charcot-Marie-Tooth disease, DI B (DNM2)
• Charcot-Marie-Tooth disease, DI C (YARS)
• 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 A (GDAP1)
• Charcot-Marie-Tooth disease, XLD, 1 (GJB1)
• 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 2F (HSPB1)
• Charcot-Marie-Tooth disease, axonal, type 2HH (JAG1)
• Charcot-Marie-Tooth disease, axonal, type 2K (GDAP1)
• Charcot-Marie-Tooth disease, axonal, type 2L (HSPB8)
• Charcot-Marie-Tooth disease, axonal, type 2M (DNM2)
• Charcot-Marie-Tooth disease, axonal, type 2N (AARS1)
• Charcot-Marie-Tooth disease, axonal, type 2O (DYNC1H1)
• Charcot-Marie-Tooth disease, axonal, type 2P (LRSAM1)
• Charcot-Marie-Tooth disease, axonal, type 2Q (DHTKD1)
• Charcot-Marie-Tooth disease, axonal, type 2T (MME)
• Charcot-Marie-Tooth disease, axonal, type 2U (MARS1)
• Charcot-Marie-Tooth disease, axonal, type 2V (NAGLU)
• 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, demyelinating, type 1G (PMP2)
• Charcot-Marie-Tooth disease, demyelinating, type 1H (FBLN5)
• Charcot-Marie-Tooth disease, type 1A (PMP22)
• Charcot-Marie-Tooth disease, type 1B (MPZ)
• Charcot-Marie-Tooth disease, type 1C (LITAF)
• 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 2B (RAB7A)
• 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 2Y (VCP)
• Charcot-Marie-Tooth disease, type 4A (GDAP1)
• Cowchock syndrome (AIFM1)
• Developmental delay, impaired growth, dysmorphic facies + axonal neuropathy (MORC2)
• Giant axonal neuropathy 2, AD (DCAF8)
• Hereditary motor + sensory neuropathy VIA (MFN2)
• Hereditary motor + sensory neuropathy, IIc (TRPV4)
• Hereditary motor and sensory neuropathy, Okinawa type (TFG)
• Hereditary neuropathies [panelapp] (KIF5A, TTR, TUBB3)
• Menkes disease (ATP7A)
• Mucopolysaccharidosis type IIIB, Sanfilippo B (NAGLU)
• Neuropathy, distal hereditary motor, type VC (BSCL2)
• Neuropathy, hereditary, with/-out age-related macular degeneration (FBLN5)
• Spinal muscular atrophy, Jokela type (CHCHD10)