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Dysfunction of NaV1.4 in Sudden Infant Death Syndrome
Study Questions:
Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. What is the prevalence of rare, functionally disrupted SCN4A variants in infants with sudden infant death syndrome (SIDS)?
Methods:
A case-control study was performed using data from the United States and the United Kingdom. The study included two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched adult controls with no history of cardiovascular, respiratory, or neurologic disease. The frequency of rare variants in SCN4A was compared between groups. Biophysical characterization of the variant channels was assessed using a heterologous expression system.
Results:
Four (1.4%) of the infants in the SIDS cohort had a functionally disruptive SCN4A variant as compared with none of the 729 matched controls (p = 0.0057).
Conclusions:
The investigators concluded that rare SCN4A variants that alter skeletal muscle sodium channels are over-represented in a cohort of SIDS cases.
Perspective:
This study investigated the prevalence of genetic variants for a skeletal muscle sodium channel in cases of SIDS as compared with a normal control group. Although over-represented as compared with the general population, these genetic variants contribute to a very small fraction (1.4%) of the cases of SIDS in this cohort. On the other hand, the study is important in identifying a potential mechanism of death in SIDS as well as a risk factor that potentially is modifiable with medical therapy.
Keywords: Genetics, Heart Defects, Congenital, Infant, Intercostal Muscles, Respiratory Muscles, Risk Factors, Sodium Channels, Sudden Infant Death, Voltage-Gated Sodium Channels
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