title: Is a shorter atrioventricular septal length an intermediate phenotype in the spectrum of nonsyndromic atrioventricular septal defects?
abstract: BACKGROUND
  Atrioventricular septal defects (AVSDs) account for 7% of all congenital cardiovascular malformations. The atrioventricular septum (AVS) is the portion of the septal tissue that separates the right atrium from the left ventricle; deficiency of the AVS contributes to the AVSD phenotype. A study of case and control families was performed to identify whether an intermediate phenotype consisting of a shortened AVS existed in relatives of children with AVSDs.
  
  
  METHODS
  AVS length (AVSL) was measured on the echocardiograms of clinically unaffected parents and siblings from families that were identified through children with nonsyndromic AVSDs and in families with no histories of congenital heart disease.
  
  
  RESULTS
  No significant differences were seen between case and control family members in terms of gender, age, weight, and height. AVSLs were significantly shorter in case parents compared with control parents. Similar findings were noted within the sibling groups. There was significant evidence for two-component distributions in the case parent, case sibling, and control sibling groups after standardizing AVSL for age and body surface area. Heritability of AVSL standardized for age and body surface area was 0.82 and 0.71 in nonsyndromic case and control families, respectively.
  
  
  CONCLUSIONS
  Evidence for two-component distributions from the analysis of AVSL standardized for age and body surface area for case parents and case siblings suggests the presence of an intermediate phenotype for nonsyndromic AVSD. The high heritability in the control families suggests that there may be polygenic involvement in the determination of AVSL. Broadening the definition of AVSD to include those with shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes for AVSD.
authors.affiliation: Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. sonali-patel@uiowa.edu
authors.forename: Sonali S
authors.initials: SS
authors.lastname: Patel
authors.forename: Larry T
authors.initials: LT
authors.lastname: Mahoney
authors.forename: Trudy L
authors.initials: TL
authors.lastname: Burns
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006344:Heart Septal Defects, Atrial / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D006346:Heart Septum / Q000000981:diagnostic imaging*; D006801:Humans; D007484:Iowa / Q000453:epidemiology; D008297:Male; D010641:Phenotype; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013577:Syndrome; D014463:Ultrasonography