CONGENITAL AXONAL NEUROPATHY CAUSED BY DELETIONS IN THE SPINAL MUSCULAR-ATROPHY REGION

Three newborn siblings presented with generalized weakness, asphyxia, facial diplegia, and external ophthalmoplegia. Electrophysiological te sting showed inexcitability of motor and sensory nerves and myographic signs of denervation. Nerve biopsies and postmortem examination showe d loss of myelinated fibers and axonal damage in sensory and mixed ner ves, Many spinal motor neurons were chromatolytic although their numbe r was normal. Molecular genetic investigations revealed a homozygous d eletion of the survival motor neuron (SMN) gene and a loss of markers Agl-CA and C212 in the paternal haplotype. These findings are consiste nt with the diagnosis of an unusually severe type of spinal muscular a trophy. Given the large extent of the deletion, it must be considered that the unusual severe phenotype with involvement of brainstem nuclei and afferent nerves might also be due to changes of yet unknown genes neighboring the SMN gene.