IllnessNeuropathy, CMT1/-4/-X, demyelinating; differential diagnosis

NGS +

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). CMT1 accounts for 2/3 of all CMT cases. 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: CMT1 + CMT4 + CMTX
• Alias: HMSNI + HMSNIV + HMSNX
• Alias: Polyneuropathie
• Allelic: Arts syndrome (PRPS1)
• Allelic: Cutis laxa, AD 2 (FBLN5)
• Allelic: Cutis laxa, AR, type IA (FBLN5)
• Allelic: Deafness, XL 1 (PRPPS1)
• Allelic: Dejerine-Sottas disease (EGR2, MPZ, PMP22, PRX)
• Allelic: Gout, PRPS-related (PRPS1)
• Allelic: Hypomyelinating neuropathy, congenital, 2 (MPZ)
• Allelic: Macular degeneration, age-related, 3 (FBLN5)
• Allelic: Mononeuropathy of the median nerve, mild (SH3TC2)
• Allelic: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
• Allelic: Roussy-Levy syndrome (MPZ, PMP22)
• Amyotrophic lateral sclerosis 11 (FIG4)
• Charcot-Marie-Tooth disease, DI D (MPZ)
• Charcot-Marie-Tooth disease, DI G (NEFL)
• Charcot-Marie-Tooth disease, RI, A (GDAP1)
• Charcot-Marie-Tooth disease, XLD, 6 (PDK3)
• Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
• Charcot-Marie-Tooth disease, axonal, type 2K (GDAP1)
• 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 1C (LITAF)
• Charcot-Marie-Tooth disease, type 1D (EGR2)
• Charcot-Marie-Tooth disease, type 1E (PMP22)
• Charcot-Marie-Tooth disease, type 1F (NEFL)
• 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 disease, type 4B1 (MTMR2)
• Charcot-Marie-Tooth disease, type 4B2 (SFB2)
• 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 neuropathy, XLD, 1 (GJB1)
• Cowchock syndrome (AIFM1)
• Hypomyelinating neuropathy, congenital, 1 (EGR2)
• Neuropathy, hereditary, with/-out age-related macular degeneration (FBLN5)
• Neuropathy, recurrent, with pressure palsies (PMP22)