IllnessNeuropathy, CMT2/HMSNII, axonal; differential diagnosis

NGS +

[[Sanger]]

Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) disorders and related neuropathies are a group of clinically and genetically heterogeneous conditions primarily affecting the peripheral nervous system with secondary muscle wasting and weakness. CMT is the most common inherited neuromuscular disorder, and patients with CMT and other HMSNs may present with many symptoms, with motor signs predominating over sensory symptoms in all age groups. Onset can occur in infancy, adolescence or throughout life with mild symptoms - even asymptomatic relatives can be detected in respective families. Motor nerve conduction velocities (NCV) distinguish two main types: CMT1 (demyelinating; NCV<35m/sec) and CMT2 (axonal; NCV>45m/sec). CMT neuropathy can be inherited either autosomal dominantly, recessively or X-linked (CMTX forms) and often occurs as a sporadic neuropathy. To date, over 60 different genetic loci have been associated with CMT1-4, CMTX and CMTdi (dominant intermediate type; NCV 35-45m/sec). Almost all of the relevant genes have been identified. These genes encode proteins involved in myelination, Schwann cell differentiation, axonal transport, endocytic recycling, mitochondrial function, protein translation, signal transduction, single-strand DNA break repair, and other processes. DNA diagnostic yields reported to date for all forms of CMT vary considerably from >20% to >60%, probably depending on the degree of clinical workup. Negative molecular genetic results by no means exclude clinical diagnosis.

Reference: 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)