Hereditary pure lower motor neuron disease with adult onset and rapid progression

We describe three members each of two families presenting with a hereditary form of lower motor neuron disease with adult onset and rapid progression and compare their pathological and clinical features with hereditary lower motor neuron disease with adult onset, as described in the literature. No i nvolvement of upper motor neurons was found either clinically or pathologic ally. Disease progression was rapid, and the majority of patients died from respiratory failure within 1-5 years after onset of disease. On pathologic al examination of the spinal cord we found ballooned neurons, neuronophagia and gliosis in family A, which have been regarded as characteristic pathol ogical features of infantile-onset spinal muscular atrophy (SMA). In family B specific neuronal changes were observed that also occur in patients with amyotrophic lateral sclerosis (ALS). An autosomal dominant mode of inherit ance would seem likely in both families. In family A the pathological findi ngs and the clinical presentation with symmetrical proximal limb weakness s how similarities with autosomal dominant SMA. Based on the finding of patho logical features in family B that also occur in ALS, together with the dist al asymmetrical muscle weakness and bulbar signs and a high age at onset we hypothesize that the members of family B suffered from familial ALS. The d isease forms in both families in our opinion further broaden the spectrum o f motor neuron disease.