ABSTRACT
Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterised by loss of motor function and muscle atrophy due to anterior horn cell degeneration. The most common variant is chromosome 5-linked proximal SMA, ranging in severity from congenital onset and infantile death to onset in adult life. Genetically separate variants with different distribution of weakness and/or additional features such as central nervous system involvement have been described. A rare variant with associated myoclonic epilepsy and lower motor neuron disease had been previously described in three families before the SMN gene, responsible for the common form of SMA, was isolated. We report four patients from two additional families affected by a syndrome characterised by severe and progressive myoclonic epilepsy and proximal weakness, tremor and lower motor neuron disease proven by electrophysiologic and muscle biopsy findings. Extensive metabolic investigations were normal and genetic analysis excluded the SMN gene. This study confirms that the association of myoclonic epilepsy and motor neuron disease represents a separate clinical and genetic entity from chromosome 5-linked SMA, the primary defect of which remains unknown.