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.