Klinische FragestellungNeuropathie, CMT/HMSN, infantil/juvenil; autosomal rezessiv; Differentialdiagnose

NGS +

[Sanger]

Unter den hereditären sensorischen und motorischen Neuropathien (Charcot-Marie-Tooth-Krankheiten; CMTs) werden einige CMT2-Subtypen, die CMT4 und einige intermediäre Formen autosomal rezessiv vererbt. In den deutschen Leitlinien (derzeit in Überarbeitung) wurden bisher 19 Entitäten explizit genannt, die im vorliegenden Genpanel enthalten sind. Diese CMTs zeigen meist den typischen Phänotyp mit fortschreitender, distal akzentuierter Schwäche/Atrophie der Muskeln der unteren Gliedmaßen, gefolgt von den Handmuskeln, sensorischen Störungen und charakteristischen Fußanomalien. CMT kann im frühen Säuglingsalter mit Hypotonie beginnen - oft mit Schwierigkeiten beim Gehen und mit Skelettdeformitäten. Die sensorischen Zeichen sind in der Regel schwächer als motorische ausgeprägt, z.B. mit Verlust des Tastempfindens und Schmerzen distal in den unteren Gliedmaßen mit reduzierten tiefen Sehnenreflexen. Frühes Auftreten und schwere (respiratorische) Komplikationen verschlechtern die Prognose quoad vitam. Die molekulargenetische Ausbeute ist hoch, aber nicht genauer bekannt, zumal erhebliche ethnische Unterschiede bestehen. Daher schließt ein negatives DNA-Testergebnis die CMT nicht mit Sicherheit aus.

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

https://www.awmf.org/uploads/tx_szleitlinien/022-027l_S1_Neuropathien_hereditaer_erworben_Kinder_Jugendliche_Differentialdiagnose.pdf

• Alias: Charcot-Marie-Tooth [CMT] hereditary neuropathy
• Alias: Hereditary motor + sensory neuropathy [HMSN]
• Alias: Polyneuropathie
• Allelic: Amyotrophic lateral sclerosis 11 (FIG4)
• Allelic: Amyotrophic lateral sclerosis 16, juvenile (SIGMAR1)
• Allelic: Amyotrophic lateral sclerosis 5, juvenile (SPG11)
• Allelic: Ataxia-oculomotor apraxia 4 (PNKP)
• Allelic: Combined oxidative phosphorylation deficiency 7 (C12orf65)
• Allelic: Combined oxidative phosphorylation deficiency 7 (MTRFR)
• Allelic: Deafness, AR 89 (KARS1)
• Allelic: Epidermolysis bullosa simplex, AR 2 (DST)
• Allelic: Hemolytic anemia due to hexokinase deficiency (HK1)
• Allelic: Leigh syndrome, due to COX IV deficiency (SURF1)
• Allelic: Lethal congenital contracture syndrome 7 (CNTNAP1)
• Allelic: Medulloblastoma (ELP1)
• Allelic: Microcephaly, seizures, developmental delay (PNKP)
• Allelic: Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
• Allelic: Myopia 6 (SCO2)
• Allelic: Neurodevelopmental disorder with visual defects + brain anomalies (HK1)
• Allelic: Polymicrogyria, bilateral temporooccipital (FIG4)
• Allelic: Pontocerebellar hypoplasia, type 1 (SLC25A46)
• Allelic: Pseudohypoaldosteronism, type IIC (WNK1)
• Allelic: Retinitis pigmentosa 79 (HK1)
• Allelic: Spastic paraplegia 55, ÁR (MTRFR)
• Allelic: Yunis-Varon syndrome (FIG4)
• Basel-Vanagait-Smirin-Yosef syndrome (MED25)
• Charcot-Marie-Tooth disease, DI G (NEFL)
• Charcot-Marie-Tooth disease, RI A (GDAP1)
• Charcot-Marie-Tooth disease, RI B (KARS1)
• Charcot-Marie-Tooth disease, RI C (PLEKHG5)
• Charcot-Marie-Tooth disease, RI D (COX6A1)
• Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
• Charcot-Marie-Tooth disease, axonal, type 2K (GDAP1)
• Charcot-Marie-Tooth disease, axonal, type 2P (LRSAM1)
• Charcot-Marie-Tooth disease, axonal, type 2S (IGHMBP2)
• Charcot-Marie-Tooth disease, axonal, type 2T (MME)
• Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
• Charcot-Marie-Tooth disease, axonal, with vocal cord paresis (GDAP1)
• Charcot-Marie-Tooth disease, type 1F (NEFL)
• Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Charcot-Marie-Tooth disease, type 2B2 (PNKP)
• Charcot-Marie-Tooth disease, type 2E (NEFL)
• Charcot-Marie-Tooth disease, type 2R (TRIM2)
• Charcot-Marie-Tooth disease, type 4A (GDAP1)
• Charcot-Marie-Tooth disease, type 4B1 (MTMR2)
• Charcot-Marie-Tooth disease, type 4B2 (SBF2)
• Charcot-Marie-Tooth disease, type 4B3 (SBF1)
• Charcot-Marie-Tooth disease, type 4C (SH3TC2)
• Charcot-Marie-Tooth disease, type 4D (NDRG1)
• Charcot-Marie-Tooth disease, type 4F (PRX)
• Charcot-Marie-Tooth disease, type 4H (FGD4)
• Charcot-Marie-Tooth disease, type 4J (FIG4)
• Charcot-Marie-Tooth disease, type 4K (SURF1)
• Congenital cataracts, facial dysmorphism + neuropathy (CTDP1)
• Dejerine-Sottas disease (EGR2, PRX)
• Dysautonomia, familial (ELP1)
• Erythermalgia, primary (SCN9A)
• Giant axonal neuropathy-1 (GAN)
• Hereditary neuropathy [panelapp] (MTRFR)
• Hypomyelinating neuropathy, congenital, 1 (EGR2)
• Hypomyelinating neuropathy, congenital, 3 (CNTNAP1)
• Insensitivity to pain, congenital (SCN9A)
• Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
• Mononeuropathy of the median nerve, mild (SH3TC2)
• NESCAV syndrome [NEurodeg., Spasticity +/- Cereb. Atrophy/cortical Visual impairment] (KIF1A)
• Neuromyotonia + axonal neuropathy, AR (HINT1)
• Neuronopathy, distal hereditary motor, type VI (IGHMBP2)
• Neuropathy, hereditary motor + sensory, Russe type (HK1)
• Neuropathy, hereditary motor + sensory, type VIA (MFN2)
• Neuropathy, hereditary motor + sensory, type VIB (SLC25A46)
• Neuropathy, hereditary sensory + autonomic, type II (WNK1)
• Neuropathy, hereditary sensory + autonomic, type IIB (RETREG1)
• Neuropathy, hereditary sensory + autonomic, type IID (SCN9A)
• Neuropathy, hereditary sensory + autonomic, type V (NGF)
• Neuropathy, hereditary sensory + autonomic, type VI (DST)
• Neuropathy, hereditary sensory + autonomic, type VIII (PRDM12)
• Neuropathy, hereditary sensory, type IIC (KIF1A)
• Paroxysmal extreme pain disorder (SCN9A)
• Peripheral neuropathy, AR, +/- impaired intellectual development (MCM3AP)
• Small fiber neuropathy (SCN9A)
• Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORD)
• Spastic ataxia, Charlevoix-Saguenay type (SACS)
• Spastic paraplegia 11, AR (SPG11)
• Spastic paraplegia 30, AD (KIF1A)
• Spastic paraplegia 55, AR (C12orf65)
• Spinal muscular atrophy, distal, AR, 2 (SIGMAR1)
• Spinal muscular atrophy, distal, AR, 4 (PLEKHG5)
• Spinal muscular atrophy, distal, AR, 5 (DNAJB2)
• Spinocerebellar ataxia 43 (MME)