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Cardiovascular malformations in Smith-Lemli-Opitz syndrome
A E Lin1, H H Ardinger, R H Ardinger
1Department of Pediatrics University of Kansas, Kansas City, USA.
Insights
Smith-Lemli-Opitz syndrome (SLOS) is linked to cardiovascular malformations (CVMs) in 44% of patients. The study classifies CVMs by embryonic mechanisms, revealing specific patterns in SLOS that impact cardiac development.
Area of Science:
- Genetics
- Developmental Biology
- Cardiology
Background:
- Smith-Lemli-Opitz syndrome (SLOS) is a genetic disorder with a complex phenotype.
- Cardiovascular malformations (CVMs) are a significant concern in SLOS patients.
- Understanding the mechanisms of CVMs in SLOS is crucial for clinical management and research.
Purpose of the Study:
- To investigate the types and frequencies of CVMs in patients with Smith-Lemli-Opitz syndrome.
- To classify CVMs based on underlying embryonic developmental mechanisms.
- To compare CVM frequencies in SLOS with a control population to identify specific developmental alterations.
Main Methods:
- Retrospective review of 215 patients with SLOS (59 new, 156 literature-based).
- Classification of CVMs according to five established embryonic mechanism categories.
- Statistical comparison of CVM frequencies in SLOS patients against the Baltimore-Washington Infant Study control group.
Main Results:
- 44% of SLOS patients exhibited CVMs.
- Class II (abnormal intracardiac blood flow) CVMs were most common (58.9%).
- Classes IV (abnormal extracellular matrix) and V (abnormal targeted growth) CVMs were significantly more frequent in SLOS compared to controls, while Class I (ectomesenchymal tissue migration) was less frequent.
Conclusions:
- CVMs in SLOS exhibit mechanistic heterogeneity, with a predominance of Class II defects.
- Developmental errors in SLOS appear to particularly affect mechanisms underlying atrioventricular canal defects and anomalous pulmonary venous return.
- Findings aid clinical geneticists in evaluating SLOS patients and guide future research into SLOS-related developmental mechanisms.
Abstract:
We reviewed 215 patients (59 new, 156 from the literature) with Smith-Lemli-Opitz syndrome (SLOS), and found that 95 (44%) had a cardiovascular malformation (CVM). Classifying CVMs by disordered embryonic mechanisms, there were 5 (5.3%) class 1 (ectomesenchymal tissue migration abnormalities), 56 (58.9%) class II (abnormal intracardiac blood flow), 25 (26.3%) class IV (abnormal extracellular matrix), and 5 (5.3%) class V (abnormal targeted growth). Comparing the frequencies of individual CVMs in this series with a control group (the Baltimore-Washington Infant Study), there were 6 individual CVMs which showed a significant difference from expected values. When frequencies of CVMs in SLOS were analyzed by mechanistic class, classes IV and V were significantly more frequent, and class I significantly less frequent, than the control group. Although CVMs in SLOS display mechanistic heterogeneity, with an overall predominance of class II CVMs, the developmental error appears to favor alteration of the cardiovascular developmental mechanisms underlying atrioventricular canal and anomalous pulmonary venous return. This information should assist the clinical geneticist evaluating a patient with possible SLOS, and should suggest research direction for the mechanisms responsible for the SLOS phenotype.