IllnessNeuropathy, hereditary motor-sensory, demyelinating, type I; 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: Charcot-Marie-Tooth type I; CMT1
• Alias: Hereditary motor sensory neuropathy, type I; HMSNI
• Alias: Polyneuropathie, erblich
• Alias: Polyneuropathy
• Allelic: Cutis laxa, AD 2 (FBLN5)
• Allelic: Cutis laxa, AR, type IA (FBLN5)
• Allelic: Diabetes, type 1, susceptibility to (ITPR3)
• Allelic: Leukodystrophy, hypomyelinating, 8, +/- oligodontia +/- hypogonadotr. hypogonadism (POLR3B)
• Allellc: Macular degeneration, age-related, 3 (FBLN5)
• Charcot-Marie-Tooth disease, demyelinating, type 1G (PMP2)
• Charcot-Marie-Tooth disease, demyelinating, type 1H (FBLN5)
• Charcot-Marie-Tooth disease, demyelinating, type 1I (POLR3B)
• Charcot-Marie-Tooth disease, demyelinating, type 1J (ITPR3)
• 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)
• Neuropathy, hereditary, +/- age-related macular degeneration (FBLN5)