Cardiac anomalies in the Simpson-Golabi-Behmel syndrome

Diverse cardiac abnormalities have been reported in patients with the Simps on-Golabi-Behmel syndrome (SGBS), and it is suspected that they are related to the apparently high incidence of early death. To clarify the incidence and significance of the various cardiac abnormalities, we reviewed 101 SGBS patients (89 from the literature, 12 new). All were male, except for one c learly affected female patient with translocation X;1 [Punnett, 1994: Am J Med Genet 50: 391-393]. Ninety-six of 99 (97%) patients had the classic phe notype of macrosomia and typical "coarse" face. Thirty-six patients (36%) h ad a cardiac abnormality, of whom 26 (26%) had a cardiovascular malformatio n (CVM). After excluding 24 patients with insufficient clinical data, these percentages among the 77 informative cases were 47% and 34%, respectively. When grouped according to a mechanistic classification, most cases (20/26, or 77%) were class II CVMs (attributed to altered embryonic intracardiac f low). Other cardiac abnormalities included cardiomyopathy (n = 4) and elect rocardiogram (ECG) conduction or rhythm abnormalities (n = 12); three of th e affected patients (25%) also had a CVM. Among 92 informative cases, there were 29 (32%) deaths, a figure that excludes seven elective terminations. Among the 25 patients younger than 3 years, death was associated with a car diac abnormality in six (23%). GPC3 mutation analysis using Southern blot t esting and polymerase chain reaction amplification was performed for 37 of 101 (37%) patients. A mutation was detected in 26 of the 37 patients tested (70%), 12 of whom (46%) had a cardiac abnormality. We conclude that cardia c abnormalities of any type are common in SGBS (almost one-half of informat ive cases), with CVMs seen in one-third of cases. The heterogeneous ECG abn ormalities in this survey must be viewed with caution, since they may repre sent a genuine component of the syndrome or reporting bias. Determining the true prevalence and natural history of cardiac abnormalities in SGBS will require a larger number of patients and more consistent prospective cardiac evaluations. There are sufficient data to recommend a baseline echocardiog ram and ECG in SGBS patients. Data are insufficient to define a cardiac phe notype/molecular correlation. Am. J. Med. Genet. 83:378-381, 1999. (C) 1999 Wiley-Liss, Inc.