Distal hereditary motor neuropathy type 2

Distal hereditary motor neuropathy type 2 (dHMN2), also known as distal spinal muscular atrophy type 2 or hereditary distal motor neuronopathy type 2, is a rare inherited neuromuscular disorder characterized by progressive weakness and wasting (atrophy) of muscles in the distal parts of the limbs, particularly the legs. The disease primarily affects the lower motor neurons — the nerve cells in the spinal cord that control voluntary muscle movement — without significant sensory nerve involvement, which distinguishes it from other hereditary neuropathies such as Charcot-Marie-Tooth disease. The condition is caused by mutations in the HSPB1 gene (encoding heat shock protein beta-1, also known as HSP27) or the HSPB8 gene (encoding heat shock protein beta-8, also known as HSP22), both of which play important roles in protein folding and cellular stress responses. Symptoms typically begin in adolescence or early adulthood, though onset can be variable. Affected individuals usually first notice difficulty walking due to weakness and atrophy of the feet and lower legs, leading to foot drop and a steppage gait. Over time, the weakness may progress to involve the hands and forearms, causing difficulty with fine motor tasks. Tendon reflexes are often reduced or absent in affected limbs. The disease is slowly progressive, and most patients remain ambulatory for many years, though some may eventually require assistive devices. Sensation is generally preserved, and upper motor neuron signs are absent. There is currently no cure or disease-modifying treatment for dHMN2. Management is supportive and symptomatic, including physical therapy to maintain muscle strength and flexibility, occupational therapy for hand function, orthotic devices such as ankle-foot orthoses to assist with foot drop, and surgical interventions for skeletal deformities if needed. Genetic counseling is recommended for affected families. Research into potential therapies targeting the underlying molecular mechanisms, including protein misfolding and aggregation pathways, is ongoing.

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