Advancing our understanding of the inheritance and transmission of pectus excavatum

Lisa Horth; Michael W. Stacey; Virginia K. Proud; Kara Segna; Chelsea Rutherford; Donald Nuss; Robert E. Kelly

doi:10.3233/PGE-2012-026

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2012; 01(03): 161-173
DOI: 10.3233/PGE-2012-026

Georg Thieme Verlag KG Stuttgart – New York

Advancing our understanding of the inheritance and transmission of pectus excavatum

Lisa Horth

^aDepartment of Biological Science, Old Dominion University, Norfolk, VA, USA

,

Michael W. Stacey

^bCenter for Bioelectrics, Old Dominion University, Norfolk, VA, USA

^cCenter for Pediatric Research, Eastern Virginia Medical School, Norfolk, VA, USA

,

Virginia K. Proud

^dDepartment of Medical Genetics and Metabolism, Children’s Hospital of The King’s Daughters and Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA, USA

,

Kara Segna

^cCenter for Pediatric Research, Eastern Virginia Medical School, Norfolk, VA, USA

,

Chelsea Rutherford

^aDepartment of Biological Science, Old Dominion University, Norfolk, VA, USA

,

Donald Nuss

^eDepartment of Surgery, Eastern Virginia Medical School and Pediatric Surgery Division, Children’s Hospital of The King’s Daughters, Norfolk, VA, USA

,

Robert E. Kelly

^eDepartment of Surgery, Eastern Virginia Medical School and Pediatric Surgery Division, Children’s Hospital of The King’s Daughters, Norfolk, VA, USA

› Author Affiliations
Subject Editor:

Abstract

PDF Download

Abstract

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum in children before severe symptoms present. Quantifying sex-ratio bias in probands demonstrates a highly significant male bias associated with pectus excavatum. When combined with pedigree data, sex-bias is indicative of sex-linked, sex-limited, and/or epigenetic control such as X-inactivation, reiterating a point made with pedigrees alone, which is that more than one mutation is likely responsible for this disorder.

Keywords

Disease - heritable - genetic - association study

PDF (563 kb)