A new form of spinal muscular atrophy

Spinal muscular atrophies with mutations in the telomeric SMN1 gene (chromosome 5q13) are one of the most frequent autosomal recessively inherited disorders. Due to a progressive loss of α-motorneurons a muscular atrophy with flaccid, proximally accentuated palsy appears. The spinal muscular atrophy with respiratory distress (SMARD1) results from a mutation in the IGHMBP2 gene (chromosome 11q13) and the first symptom is often weakness of the diaphragm and respiratory insuffiency.

We present two affected siblings from consanguineous parents with a so far unknown spinal muscular atrophy. The patients presented at the age of 13 and 15 years with a slowly progressive, proximal muscular palsy, while the facial muscles seem unaffected. In addition, the girl presents with splenomegaly, the boy with hepatosplenomegaly and tapetoretinal degeneration. Results from NCVs, EMGs, muscle- and nervebiopsies showed neurogenic lesions with moderate signs of demyelination. The parents and five siblings are healthy. Different haplotypes for chromosome 5q and 11q make the diagnosis of juvenile spinal muscular atrophy or SMARD unlikely. On the basis of consanguineous parents and the different sexes of the siblings we hypothesize an autosomal recessive inheritance. We used the Affymetrix-SNP-chip technology for a genomewide linkage-analysis and identified a single locus. To further characterize this unknown form of spinal muscular atrophy we are looking for other patients with a similar phenotype.