Transient QT interval prolongation in an infant with Simpson–Golabi–Behmel syndrome

Abstract

Simpson–Golabi–Behmel syndrome (SGBS, OMIM #312870) is a rare X-linked overgrowth syndrome resulting from mutations in the GPC3 gene [Pilia et al., 1996]. SGBS is characterized by preand post-natal macrosomia, coarse facial features, varying degrees of intellectual impairment, cardiac and hand abnormalities, and an increased risk of embryonic cancers. Diagnosis in these patients can be challenging due to variability in clinical presentation, a small number of known patients, and overlap with other syndromic conditions. Timothy syndrome (OMIM #601005), also known as type 8 long QT syndrome (LQT8), is one of many syndromes that shares some common features with SGBS. Timothy syndrome is a cardiac channelopathy caused by a mutation in the CACNA1C gene of 12p13.3 resulting in marked QT interval prolongation and risk for sudden death [Splawski et al., 2004]. Additional clinical findings in Timothy syndrome include syndactyly, congenital heart disease, immune deficiency and cognitive abnormalities. We report on a male infant who presented elsewhere with transient QT interval prolongation and syndactyly that prompted an initial diagnosis of Timothy syndrome rather than the subsequent clinically suspected and genetically confirmed diagnosis of SGBS. We also describe the phenotype of his carrier mother and his prenatal findings that may be characteristic of SGBS and could potentially help in prenatal diagnosis.