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Cardiac anomalies in the Simpson-Golabi-Behmel syndrome
A E Lin1, G Neri, R Hughes-Benzie
1Genetics and Teratology Unit, Massachusetts General Hospital, Boston 02114, USA. lin.angela@mgh.harvard.edu
Insights
Cardiac abnormalities are common in Simpson-Golabi-Behmel syndrome (SGBS), affecting nearly half of patients. Cardiovascular malformations are present in one-third, highlighting the need for baseline cardiac screening in SGBS patients.
Area of Science:
- Genetics and Developmental Biology
- Cardiology
- Clinical Medicine
Background:
- Simpson-Golabi-Behmel syndrome (SGBS) is associated with diverse cardiac abnormalities and high early mortality.
- Previous reports suggest a link between cardiac issues and mortality in SGBS, but incidence and significance require clarification.
Purpose of the Study:
- To determine the incidence and significance of cardiac abnormalities in Simpson-Golabi-Behmel syndrome (SGBS).
- To investigate the relationship between cardiac findings, GPC3 mutations, and clinical outcomes in SGBS patients.
Main Methods:
- Retrospective review of 101 Simpson-Golabi-Behmel syndrome (SGBS) patients (89 literature, 12 new).
- Analysis of cardiac abnormalities, cardiovascular malformations (CVMs), cardiomyopathy, and electrocardiogram (ECG) findings.
- GPC3 mutation analysis using Southern blot and polymerase chain reaction in a subset of patients.
Main Results:
- Cardiac abnormalities were found in 47% of informative SGBS cases, with cardiovascular malformations (CVMs) in 34%.
- Class II CVMs (altered embryonic intracardiac flow) comprised 77% of cardiovascular malformations.
- GPC3 mutations were detected in 70% of tested patients, with 46% of those having cardiac abnormalities.
Conclusions:
- Cardiac abnormalities are frequent in Simpson-Golabi-Behmel syndrome (SGBS), necessitating baseline echocardiogram and ECG screening.
- Cardiovascular malformations are a significant component of cardiac involvement in SGBS.
- Further research with larger cohorts and consistent cardiac evaluations is needed to define the cardiac phenotype and molecular correlations.
Abstract:
Diverse cardiac abnormalities have been reported in patients with the Simpson-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 clearly 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 phenotype of macrosomia and typical "coarse" face. Thirty-six patients (36%) had a cardiac abnormality, of whom 26 (26%) had a cardiovascular malformation (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 flow). Other cardiac abnormalities included cardiomyopathy (n = 4) and electrocardiogram (ECG) conduction or rhythm abnormalities (n = 12); three of the 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 cardiac abnormality in six (23%). GPC3 mutation analysis using Southern blot testing 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 cardiac abnormalities of any type are common in SGBS (almost one-half of informative cases), with CVMs seen in one-third of cases. The heterogeneous ECG abnormalities in this survey must be viewed with caution, since they may represent 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 echocardiogram and ECG in SGBS patients. Data are insufficient to define a cardiac phenotype/molecular correlation.