What is the epidemiology of Spinal Muscular Atrophy (SMA)?

Epidemiology of Spinal Muscular Atrophy (SMA)

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder with an estimated incidence of 1 in 6,000 to 1 in 10,000 live births and a carrier frequency of approximately 1 in 40-60 individuals. 1, 2

Genetic Basis and Prevalence

• SMA is caused by homozygous mutations or deletions of the survival motor neuron 1 (SMN1) gene located on chromosome 5q13, resulting in degeneration of alpha motor neurons in the spinal cord 2
• Approximately 94% of clinically typical SMA patients have a homozygous absence of SMN1 exon 7 due to gene deletion or conversion 3
• The remaining 6% of SMA cases have small intragenic SMN1 mutations or may have SMA unrelated to SMN1 3
• The SMN2 gene, a homologue of SMN1, is retained in all SMA patients and produces low levels of functional SMN protein, but cannot fully compensate for the mutated SMN1 1

Global Distribution and Demographics

• The prevalence of SMA varies slightly by region but remains one of the most common autosomal recessive disorders worldwide 2
• Carrier frequency is consistently high across populations at approximately 1 in 40-60 individuals 1, 2
• SMA affects all ethnic groups, with no known significant differences in incidence between populations 2

Clinical Classification

SMA is classified into four main phenotypic categories based on age of onset and motor function achieved:

• Type I (Werdnig-Hoffmann disease): Severe infantile form with onset before 6 months and high mortality within the first year 2
• Type II: Intermediate form with onset between 6-18 months 2
• Type III (Kugelberg-Welander disease): Mild form with onset after 18 months 2
• Type IV: Adult-onset form with mild motor impairment 2

Diagnostic Testing

• The primary diagnostic test demonstrates homozygous deletion of the SMN1 gene, typically showing absence of SMN1 exon 7 2
• This test achieves up to 95% sensitivity and nearly 100% specificity 2
• SMN gene dosage analysis can determine copy numbers of both SMN1 and SMN2 genes, which is important for carrier testing and prognosis 3
• Comprehensive genetic testing includes PCR-RFLP assay, SMN gene dosage analysis, and linkage analysis in certain cases 3

Screening Considerations

• Due to the high carrier frequency, population-wide newborn and carrier screening has been proposed 1
• Carrier testing is frequently requested by siblings of patients or parents of affected children to assist with reproductive planning 2
• Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%) 2

Associated Complications

• SMA patients frequently experience malnutrition, with studies showing up to 65% of patients being malnourished 4
• Nutritional deficiencies, particularly calcium absorption issues, have been documented in up to 84% of patients in some populations 4
• Gut microbiota alterations have been observed in SMA patients compared to healthy controls, which may play a role in disease progression 4

Understanding the epidemiology of SMA is crucial for appropriate genetic counseling, early diagnosis, and developing targeted therapeutic strategies for this devastating neuromuscular disorder.