Charcot-Marie-Tooth Disease: Genetic Causes, Types, and Management
Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies (prevalence ~1:2,500). It affects motor and sensory nerves, causing progressive distal weakness and sensory loss.
Genetic Classification (Major Types)
| Type | Inheritance | Gene | Pathology | Key Features |
|---|
| CMT1A | AD | PMP22 dup (17p12) | Demyelinating | Most common (~50% CMT); onset 1st–2nd decade; slow progression |
| CMT1X | XL | GJB1 (Cx32) | Demyelinating | Males more severe; females variable; CNS involvement possible |
| CMT2A | AD | MFN2 | Axonal | Early onset, severe; optic atrophy common |
| CMT4C | AR | SH3TC2 | Demyelinating | Childhood onset; scoliosis, cranial nerve involvement |
Over 100 genes implicated; AD, AR, XL patterns. Genetic testing confirms diagnosis and guides counseling.
Clinical Hallmarks
- Distal muscle wasting ("stork legs," "inverted champagne bottle" calves).
- Foot deformities: pes cavus, hammer toes, foot drop.
- Gait: steppage, frequent tripping.
- Sensory loss: stocking-glove distribution.
- Hand weakness (thenar wasting) later.
- Absent deep tendon reflexes.
Management (Multidisciplinary)
- PT/OT: Stretching, strengthening, AFOs, assistive devices.
- Orthopedic: Tendon transfers, osteotomies for fixed deformities.
- Pain management: Neuropathic agents (gabapentin, duloxetine).
- Genetic counseling: Recurrence risk, prenatal/preimplantation options.
- Surveillance: Pulmonary (rare diaphragmatic involvement), cardiac (some types).
Emerging Therapies
Gene therapy (AAV-PMP22 shRNA for CMT1A), antisense oligonucleotides, small molecules targeting proteostasis — in clinical trials.
CMT is lifelong but manageable; early intervention preserves function and independence.
Premenstrual Syndrome (PMS) - Related Articles
