This article reviews the various aspects (clinical, genetic, pathophysiological and therapeutic) of this group of heterogeneous inherited diseases characterized by slowly progressive pure distal motor neuropathy and normal motor and sensory conduction velocities.
Over thirty genes are associated with these purely motor pathologies, which Harding classified into seven major clinical groups:
- four with autosomal dominant transmission (types I, II, V and VII) and three with autosomal recessive transmission (types III, IV and VI);
- types I (juvenile onset) and II (adult onset) present as amyotrophy and distal muscle weakness of the lower limbs;
- type V as distal muscular amyotrophy and weakness, predominantly in the upper limbs;
- type VII manifests as vocal cord paralysis associated with distal weakness of all four limbs.
This review integrates genetic findings with Harding’s classification. It highlights the diversity of altered cellular functions, as well as the clinical overlap of distal hereditary motor neuropathies with Charcot-Marie-Tooth disease type 2 or juvenile forms of familial amyotrophic lateral sclerosis. Physiotherapy and splinting remain the mainstay of treatment for these conditions.
