TY - JOUR
T1 - Cardiovascular malformations in Smith-Lemli-Opitz syndrome
AU - Lin, Angela E.
AU - Ardinger, Holly H.
AU - Ardinger, Robert H.
AU - Cunniff, Christopher
AU - Kelley, Richard I.
PY - 1997/2/27
Y1 - 1997/2/27
N2 - 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 I (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.
AB - 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 I (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.
KW - MCA/MR syndrome
KW - Smith-Lemli-Opitz syndrome
KW - anomalous pulmonary venous return
KW - atrioventricular canal
KW - cardiovascular malformation
KW - congenital heart defect
KW - mechanistic classification
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U2 - 10.1002/(SICI)1096-8628(19970131)68:3<270::AID-AJMG5>3.0.CO;2-Q
DO - 10.1002/(SICI)1096-8628(19970131)68:3<270::AID-AJMG5>3.0.CO;2-Q
M3 - Article
C2 - 9024558
AN - SCOPUS:0031056983
SN - 0148-7299
VL - 68
SP - 270
EP - 278
JO - American journal of medical genetics
JF - American journal of medical genetics
IS - 3
ER -