Motor neuron disease due to neuropathy target esterase gene mutation: Clinical features of the index families

Abstract Recently, we reported that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive motor neuron disease (NTE‐MND). We describe clinical, neurophysiologic, and neuroimaging features of affected subjects in the index families. NTE‐MND subjects exhibited progressive lower extremity spastic weakness that began in childhood and was later associated with atrophy of distal leg and intrinsic hand muscles. NTE‐MND resembles Troyer syndrome, except that short stature, cognitive impairment, and dysmorphic features, which often accompany Troyer syndrome, are not features of NTE‐MND. Early onset, symmetry, and slow progression distinguish NTE‐MND from typical amyotrophic lateral sclerosis. NTE is implicated in organophosphorus compound–induced delayed neurotoxicity (OPIDN). NTE‐MND patients have upper and lower motor neuron deficits that are similar to OPIDN. Motor neuron degeneration in subjects with NTE mutations supports the role of NTE and its biochemical cascade in the molecular pathogenesis of OPIDN and possibly other degenerative neurologic disorders. Muscle Nerve, 2011