SMA

 

 

Spinal Muscular Atrophy (SMA)

The childhood spinal muscular atrophy (SMA) is an autosomal recessive diseases with prevalence of 1 in 6000 new-borns in Caucasian population. SMA is characterized by degeneration of the anterior horn cells of the spinal cord. The nerves controlling the proximal voluntary muscle movements such as locomotion are destroyed. Three different clinical syndromes are defined on the basis of severity of illness, but the classes overlap. SMA type I (Werdnig-Hoffmann disease; severe  or acute SMA) is the most severe form, with onset of symptoms at birth to several months of age. These children never raise their heads or sit unsupported. They usually die within the first three years of life because of recurrent respiratory infections. SMA types II (intermediate) and III (mild SMA; Kugelberg-Welander) are clinically more heterogeneous, with onset ranging from 3 months to 17 years. All three forms have been genetically mapped to chromosome 5q11.2-q13.3.  In SMA type II onset is usually between 3 and 15 month of age and these children learn to sit without support but can never stand or walk without aided

 

SMA affects all ethnic groups. Collective carrier frequency of types I, II and III is estimated to be between 1 in 40 and 1 in 80. SMA is the most common recessive disorder after cystic fibrosis and PKU deficiency.

 

Molecular basis

All three forms of SMA have been genetically mapped to chromosome 5q11.2-q13.3. Lefebvre et al. (1995) and Roy et al. (1995) have described the gnomic structure of the SMA locus, although both grope identified a different gene. The region is characterised by the inverted duplication of about 500 kb. SMA patients have deletions in the telomeric repeating unit. A gene was identified in this region is called SMN. There is an almost identical copy of this gene in the centromeric repeating unit (BCD541).

 

Lefebvre et al. (1995) have found that in 98.6% of  patients with SMA, regardless of the severity type, the SMN gene is deleted, thus allowing for a diagnostic test. In the in the remaining patients (1.4 %) in which no deletion of this gene could be shown, point mutations in the SMN gene may indeed cause SMA. Thus far, the molecular basis for the different severity of SMA types I, II and III cases is not known. Limited evidence suggests that it has to do with the size of the deletion in this region of duplicated genes on chromosome 5.

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