Spinal Muscular Atrophy in the Chinese

Spinal muscular atrophy (SMA) is a hereditary disorder characterized by degeneration of the anterior horn cells. SMA was first reported by Hoffmann 1 and Werdnig 2, who described neonates with profound muscle wasting and flaccid paralysis. The gene locus was mapped to chromosome 5q11.2~q13.3 in 1995, and deletion or mutation in the survival motor neuron gene (SMN) was identified 3. The diagnosis can be confirmed by genetic testing in most cases by determining the homozygous deletion or point mutation of the SMN1 gene (telomeric copy), thus avoiding the invasive muscle biopsy in clinically suspicious cases. The clinical severity is partly determined by the copy number of the SMN2 gene (centromeric copy) with an inverse relationship between copy number and disease severity. The SMN2 mRNA, which lacks Exon 7, results in a truncated and less stable protein; thus, methods to increase SMN2-derived protein production is an important focus for therapeutic trials 4.

Abstract

Spinal muscular atrophy (SMA) is one of the common neuromuscular disorders in children. In this review, the classification, phenotype, genetics, and management strategy for Chinese SMA patients are discussed, together with insights on new treatment modalities and prospective trials. SMA is an autosomal-recessive disorder with progressive muscle weakness and fatal outcome in many severely affected cases. Thus, identification of the otherwise healthy and asymptomatic carriers is of paramount importance toward prevention of the disease by prenatal diagnosis. Carrier testing among family members and even population screening should be advocated. Different methods of carrier testing to detect heterozygous deletion of the SMN1 gene, gene mutation, the 2+0 SMN1 genotype, and assessment of relative gene dosage of SMN1 and SMN2 are considered.

Keywords

SMA, SMN1, SMN2, carrier testing, children, Chinese