Nelson Textbook of Pediatrics 22nd Edition โ CMT1A (PMP22 duplication, demyelinating, slow NCV), CMT2 (axonal, MFN2), CMTX1 (GJB1/connexin-32), HNPP (PMP22 deletion, pressure palsies), Dejerine-Sottas (severe infantile), Refsum disease (phytanic acid), giant axonal neuropathy (GAN), Fabry disease (ฮฑ-galactosidase A).
๐ paeds.online โ Pakistan's Pediatric Platform| Type | Gene/Locus | Protein | Inheritance | NCV (motor) | Key Features |
|---|---|---|---|---|---|
| CMT1A (most common) | PMP22 duplication (17p11.2) | Peripheral myelin protein 22 | AD | Slow (<38 m/s) | Onset childhood, distal weakness, pes cavus, sensory loss, palpably enlarged nerves |
| HNPP | PMP22 deletion | PMP22 | AD | Mild slowing | Episodic pressure palsies (carpal tunnel, peroneal), tomaculous neuropathy |
| CMT1B | MPZ (P0) | Myelin protein zero | AD | Slow | Variable, infantile to adult |
| CMT2A (most common axonal) | MFN2 (1p36) | Mitofusin 2 | AD | Normal or mildly reduced | Axonal, onset childhood, optic atrophy (some) |
| CMTX1 | GJB1 (Xq13.1) | Connexin-32 | X-linked | Intermediate (25-45) | Males more severe, CNS symptoms (transient weakness), deafness |
| Dejerine-Sottas (CMT3) | PMP22, MPZ, EGR2 | Various | AD/AR | Very slow (<10 m/s) | Severe infantile onset, hypotonia, delayed motor milestones |
| Refsum disease | PHYH, PEX7 | Phytanoyl-CoA hydroxylase | AR | Slow | Retinitis pigmentosa, ataxia, ichthyosis, deafness, elevated phytanic acid, dietary restriction |
| Giant axonal neuropathy | GAN (16q24) | Gigaxonin | AR | Axonal | Kinky hair, CNS white matter changes, giant axons on biopsy |
| Fabry disease | GLA (Xq22) | ฮฑ-Galactosidase A | X-linked | Normal or mild | Acroparesthesias, angiokeratomas, renal/cardiac, enzyme replacement |
CMT1A (PMP22 duplication): Most common CMT (70% of CMT1). Slow nerve conduction (<38 m/s). Palpably enlarged nerves, pes cavus, hammer toes.
HNPP (PMP22 deletion): Episodic mononeuropathies (carpal tunnel, peroneal palsy) after minor trauma. Sural nerve biopsy: tomaculous (sausage-shaped) myelin thickenings.
CMTX1 (GJB1): Males more severely affected. Transient CNS symptoms (dysarthria, weakness) due to CNS involvement. Intermediate NCV.
Refsum disease: Elevated plasma phytanic acid (due to impaired ฮฑ-oxidation). Treat with dietary restriction of phytanic acid (avoid spinach, nuts, dairy).
Giant axonal neuropathy: Kinky/frizzy hair (tightly curled), CNS white matter changes on MRI, nerve biopsy shows giant axons (neurofilament accumulation).