Clinical and molecular genetic features of congenital spinal muscular atrophy

A neonate presented with the fetal hypokinesia sequence and signs of spinal muscular atorphy (SMA). Severe pathological changes including ballooned neurons and neuronophagia were found not only in themotor nerve nuclei but also in the thalamic, cerebellar, and brainstem nuclei as well as in the dorsal root ganglia. Direct DNA analysis showed the presence of chimeric SMN gene, with a rearrangment occurring between exon 7 of the centromeric SMN gene and exon 8 of the telomeric SMN gene. Circumstantial evidence suggests that only a single copy of this gene is present, with transciriptional characeristics of a centromeric SMN gene. In addition, a homozygous deletion in the NAIP genes was demonstrated. This observation demonstrates that at least some cases with fetal hypokinesia and SMA may represent the severe end of a spectrum of disorders caused by deletions in the SMA locus on chromosome 5q13. In addition, these findigns are compatible with a modifying role for the centromeric SMN genes and the NAIP genes in the severitiy of the SMA phenotype.