Angle B, Tint G S, Yacoub O A, Clark A L
Child Evaluation Center, Department of Pediatrics, University of Louisville, Kentucky 40202, USA.
Am J Med Genet. 1998 Dec 4;80(4):322-6.
Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder comprised of recognizable facial abnormalities, growth retardation, and multiple congenital anomalies, commonly involving genitalia, second and third toe syndactyly, and cleft palate. The condition is associated with hypocholesterolemia and elevated levels of 7-dehydrocholesterol (7DHC) resulting from deficient activity of the enzyme 7-dehydrocholesterol reductase. The clinical spectrum of SLO ranges from individuals with mental retardation and minor anomalies to those with major structural defects and early or even prenatal lethality. Low maternal serum unconjugated estriol (uE3) levels and a variety of fetal ultrasound anomalies have been identified in affected pregnancies, and prenatal diagnosis is possible by measurement of amniotic fluid 7DHC levels in pregnancies known to be at risk because of a previously affected child. We report on a pregnancy with low maternal uE3 level, abnormal antenatal ultrasound findings including limb deformities, ventriculomegaly, and hydrops fetalis, and a normal 46,XY karyotype. The infant died at birth. At autopsy the infant had hydrops, unusual face, cleft palate, genital abnormalities, Dandy-Walker malformation, and absence of toe syndactyly. Tests performed on cultured skin fibroblasts showed elevated levels of 7DHC and abnormalities of cholesterol biosynthesis characteristic of the metabolic defect that causes SLO. The atypical findings of hydrops, uncharacteristic facial appearance, and absence of toe syndactyly in this case additionally illustrates the wide phenotypic spectrum of SLO and the need for a high index of suspicion for a disorder with great clinical variability. Identification of another affected pregnancy with a low maternal uE3 level and abnormal fetal ultrasound findings in the presence of a normal karyotype lends additional support for consideration of prenatal biochemical testing for SLO in pregnancies with these findings, including pregnancies not previously known to be at risk.
史密斯-利姆利-奥皮茨（SLO）综合征是一种常染色体隐性疾病，其特征包括可识别的面部异常、生长发育迟缓以及多种先天性畸形，常见的有生殖器异常、第二和第三趾并指以及腭裂。该病症与低胆固醇血症以及由于7-脱氢胆固醇还原酶活性不足导致的7-脱氢胆固醇（7DHC）水平升高有关。SLO的临床谱范围广泛，从有智力障碍和轻微异常的个体到有严重结构缺陷以及早期甚至产前致死的个体。在受影响的妊娠中已发现母体血清未结合雌三醇（uE3）水平降低以及多种胎儿超声异常，对于因之前有患病儿童而已知有风险的妊娠，通过测量羊水7DHC水平可进行产前诊断。我们报告了一例妊娠，其母体uE3水平低，产前超声检查结果异常，包括肢体畸形、脑室扩大和胎儿水肿，且核型为正常的46,XY。婴儿出生时死亡。尸检发现婴儿有水肿、面容异常、腭裂、生殖器异常、丹迪-沃克畸形以及无趾并指。对培养的皮肤成纤维细胞进行的检测显示7DHC水平升高以及胆固醇生物合成异常，这是导致SLO的代谢缺陷的特征。该病例中水肿、不典型面容以及无趾并指的非典型表现进一步说明了SLO广泛的表型谱以及对于具有很大临床变异性的疾病需要高度怀疑。在核型正常的情况下，识别出另一例母体uE3水平低且胎儿超声检查结果异常的受影响妊娠，为在有这些发现的妊娠中，包括之前未知有风险的妊娠，考虑对SLO进行产前生化检测提供了额外支持。
