Klinische FragestellungNeuronopathie/Muskelatrophie, distale hereditäre; Differentialdiagnose

NGS +

Distale hereditäre motorische Neuropathien (dHMN) sind klinisch und genetisch heterogene Erkrankungen, die durch eine Funktionsstörung der unteren Motoneuronen verursacht werden.- Der klassische Phänotyp einer dHMN ist eine längenabhängige motorische Schwäche und Atrophie, die zunächst die intrinsischen Fußmuskeln und das Peronealkompartiment des Beins betrifft und häufig zu Fußdeformitäten wie Hohlfuß, Planfuß und Krallenstellung der Zehen führt. In den meisten Fällen zeigt sich ein langsam fortschreitender Krankheitsverlauf, der nach und nach die proximalen Beinmuskeln oder die intrinsischen Handmuskeln betrifft. Variables Erkrankungsalter, unterschiedlicher klinischer Verlauf und damit verbundene neurologische Merkmale komplizieren den Phänotyp und führen zur klinische Unterklassifizierung. Derzeit sind rund 30 Gene bekannt, die für autosomal-dominante, rezessive und X-chromosomale Formen der dHMN verantwortlich sind.

Literatur: https://www.neurology.org/doi/pdf/10.1212/WNL.0000000000003772

• Alias: dHMN distal Hereditary MotoNeuropathy
• Allelic: Alpha-aminoadipic + alpha-ketoadipic aciduria (DHTKD1)
• Allelic: Amyotrophic lateral sclerosis 8 (VAPB)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to (DCTN1)
• Allelic: Androgen insensitivity (AR)
• Allelic: Androgen insensitivity, partial, +/- breast cancer (AR)
• Allelic: Boucher-Neuhauser syndrome (PNPLA6)
• Allelic: Developmental and epileptic encephalopathy 29 (AARS1)
• Allelic: Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• Allelic: Farber Lipogranulomatosis (ASAH1)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
• Allelic: Hypospadias 1, XL (AR)
• Allelic: Leukoencephalopathy, hereditary diffuse, with spheroids 2 (AARS1)
• Allelic: Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Allelic: Muscular dystrophy, congenital, Davignon-Chauveau type (TRIP4)
• Allelic: Myasthenic syndrome, congenital, 20, presynaptic (SLC5A7)
• Allelic: Myopathy, isolated mitochondrial, AD (CHCHD10)
• Allelic: Primary lateral sclerosis, juvenile (ALS2)
• Allelic: Trichothiodystrophy 8, nonphotosensitive (AARS1)
• Allelic: VEXAS syndrome, somatic (UBA1)
• Amyotrophic lateral sclerosis 2, juvenile (ALS2)
• Amyotrophic lateral sclerosis 5, juvenile (SPG11)
• Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• Charcot-Marie-Tooth disease, axonal, type 2F (HSPB1)
• Charcot-Marie-Tooth disease, axonal, type 2L (HSPB8)
• Charcot-Marie-Tooth disease, axonal, type 2N (AARS1)
• Charcot-Marie-Tooth disease, axonal, type 2Q (DHTKD1)
• Charcot-Marie-Tooth disease, axonal, type 2S (IGHMBP2)
• Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
• Charcot-Marie-Tooth disease, type 2D (GARS1)
• Distal hereditary motor neuropathy
• Distal spinal muscular atrophy
• Fazio-Londe disease (SLC52A3)
• Hereditary motor + sensory neuropathy VIA (MFN2)
• Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Laurence-Moon syndrome (PNPLA6)
• Myasthenic syndrome, congenital, 7A, presynaptic, distal motor neuropathy, AD (SYT2)
• Myasthenic syndrome, congenital, 7B, presynaptic, AR (SYT2)
• Neuronopathy, distal hereditary motor, type IIA (HSPB8)
• Neuronopathy, distal hereditary motor, type IIB (HSPB1)
• Neuronopathy, distal hereditary motor, type IIC (HSPB3)
• Neuronopathy, distal hereditary motor, type IID (FBXO38)
• Neuronopathy, distal hereditary motor, type IX (WARS1)
• Neuronopathy, distal hereditary motor, type VA (GARS1)
• Neuronopathy, distal hereditary motor, type VB (REEP1)
• Neuronopathy, distal hereditary motor, type VI (IGHMBP2)
• Neuronopathy, distal hereditary motor, type VIIA (SLC5A7)
• Neuronopathy, distal hereditary motor, type VIIB (DCTN1)
• Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Neuropathy, distal hereditary motor, type VA (BSCL2)
• Oliver-McFarlane syndrome (PNPLA6)
• Perry syndrome (DCTN1)
• Pontocerebellar hypoplasia type 1A (VRK1)
• Pontocerebellar hypoplasia, type 1B (EXOSC3)
• Pontocerebellar hypoplasia, type 1C (EXOSC8)
• SMA, distale Form
• Silver spastic paraplegia syndrome (BSCL2)
• Slowed nerve conduction velocity, AD (ARHGEF10)
• Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORD)
• Spastic paralysis, infantile onset ascending (ALS2)
• Spastic paraplegia 11, AR (SPG11)
• Spastic paraplegia 31, AD (REEP1)
• Spastic paraplegia 39, AR (PNPLA6)
• Spinal + bulbar muscular atrophy of Kennedy (AR_CAG)
• Spinal and bulbar muscular atrophy of Kennedy (AR)
• Spinal muscular atrophy with congenital bone fractures 1 (TRIP4)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Spinal muscular atrophy, Jokela type (CHCHD10)
• Spinal muscular atrophy, XL 2, infantile (UBA1)
• Spinal muscular atrophy, distal, AR, 2 (SIGMAR1)
• Spinal muscular atrophy, distal, AR, 4 (PLEKHG5)
• Spinal muscular atrophy, distal, AR, 5 (DNAJB2)
• Spinal muscular atrophy, distal, XL 3 (ATP7A)
• Spinal muscular atrophy, late-onset, Finkel type (VAPB)
• 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-1, -2, -3, -4 (SMN1)