RESUMO
BACKGROUND & OBJECTIVES: Distal upper limb spinal muscular atrophy (SMA) is an uncommon segmental variant of SMA. The condition is usually sporadic, affects males more often than females, and manifests late in the second decade of life, remaining confined to the upper limbs. We examined four patients with this form of SMA in order to determine if they carried homozygous deletion mutations in the survival motor neuron (SMN) or neuronal apoptosis inhibitory protein (NAIP) genes that underlie proximal SMA. METHODS: The four patients with distal upper limb SMA were analysed clinically, electrophysiologically and biochemically. Genomic DNA from each of the patients was analysed by restriction enzyme digestion of polymerase chain reaction (PCR) amplification products, as well single stranded conformation polymorphism (SSCP), to detect deletion events of selected exons of the SMN and NAIP genes. RESULTS: The clinical phenotype of the four patients, together with the biochemical and electrophysiological studies, confirmed a diagnosis of distal upper limb SMA. The molecular studies excluded homozygous deletion mutations in these patients as causative of their phenotype. INTERPRETATION & CONCLUSION: The genetic component underlying distal upper limb SMA appears not to involve mutations that are common in proximal SMA patients. It is possible that genes other than SMN and NAIP may be involved, while somatic mosaicism of SMN gene mutations could be implicated in the segmental nature of distal upper limb SMA.