Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development

Pediatr Res. 2004 Sep;56(3):391-5. doi: 10.1203/01.PDR.0000136285.91048.4A. Epub 2004 Jul 7.


We have previously identified polymorphisms in the serotonin transporter gene promoter region and in intron 2 that were more common among sudden infant death syndrome (SIDS) cases compared with control subjects. To elucidate further the genetic profile that might increase an infant's vulnerability to SIDS, we focused on the recognized relationship between autonomic nervous system (ANS) dysregulation and SIDS. We therefore studied genes pertinent to early embryologic development of the ANS, including MASH1, BMP2, PHOX2a, PHOX2b, RET, ECE1, EDN1, TLX3, and EN1 in 92 probands with SIDS and 92 gender- and ethnicity-matched control subjects. Eleven protein-changing rare mutations were identified in 14 of 92 SIDS cases among the PHOX2a, RET, ECE1, TLX3, and EN1 genes. Only 1 of these mutations (TLX3) was identified in 2 of 92 control subjects. Black infants accounted for 10 of these mutations in SIDS cases and 2 control subjects. Four protein-changing common polymorphisms were identified in BMP2, RET, ECE1, and EDN1, but the allele frequency did not differ between SIDS cases and control subjects. However, among SIDS cases, the allele frequency for the BMP2 common polymorphism demonstrated ethnic differences; among control subjects, the allele frequency for the BMP2 and the ECE1 common polymorphisms also demonstrated ethnic differences. These data represent further refinement of the genetic profile that might place an infant at risk for SIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autonomic Nervous System* / growth & development
  • Autonomic Nervous System* / physiology
  • Case-Control Studies
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology*
  • Ethnicity
  • Homeodomain Proteins / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Genetic*
  • Risk Factors
  • Sudden Infant Death / ethnology
  • Sudden Infant Death / genetics*
  • Transcription Factors / genetics


  • Homeodomain Proteins
  • NBPhox protein
  • Nerve Tissue Proteins
  • Transcription Factors