A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy

Aims: To describe the occurrence of spinal muscular atrophy (SMA) in childhood; to evaluate if any of the genes in the SMA region on chromosome 5q13 correlates with disease severity; to make genotype-phenotype correlations; to evaluate the variability of different disease alleles in carriers and the sensitivity of multiplex ligation-dependent probe amplification (MLPA) for detecting carriers. Methods: In a population-based study from Western Sweden MLPA was used to determine the copy-numbers of several genes in the SMA region (SMN1, SMN2, BIRC1, GTF2H2 and SERF1A) in SMA-patients and their parents. Results: We estimated the incidence of SMN1-related SMA in childhood at 1 in 11 800 live births and confirmed the relationship between the number of SMN2 copies and the severity of disease. No other direct relationships were found. All but one of the analysed parents were confirmed as carriers by MLPA analysis. A total of at least 30 different disease alleles were identified and no specific disease allele represented more than 15% of the total. Conclusion: The childhood incidence of SMA in the Swedish population is around 1 in 12 000 live births and it is unlikely that there is any founder effect involved in SMA in western Sweden.