Smith-Lemli-Opitz syndrome: Phenotype, natural history, and epidemiology
Smith-Lemli-Opitz syndrome: Phenotype, natural history, and epidemiology
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DOI：
10.1002/ajmg.c.31343
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发表时间：
2012-11-15
影响因子：
3.1
通讯作者：
Irons, Mira B.
中科院分区：
文献类型：
--
作者：
Nowaczyk, Malgorzata J. M.;Irons, Mira B.
SmithLemliOpitz综合征（SLOS）是一种先天性多发性异常/智力残疾综合征，由DHCR 7编码的7-脱氢胆固醇（7 DHC）还原酶缺乏引起的胆固醇合成缺乏引起。SLOS以常染色体隐性模式遗传。其特征是产前和产后生长迟缓、小头畸形、不同程度的智力残疾（包括正常智力到严重智力缺陷）以及多种大小畸形。外部畸形包括独特的面部特征，腭裂，轴后多指（趾）畸形，脚趾并指（趾）畸形和男性外生殖器发育不全，而内部异常可能影响每个器官系统。临床范围很广，很少有个体发育正常，只有轻微畸形。SLOS的临床诊断通过证明血清或其他组织中胆固醇前体7 DHC的浓度异常升高或通过存在两个DHCR 7突变来证实。酶缺乏导致胆固醇降低和7 DHC水平升高，无论是在胚胎发育期间还是出生后。在SLOS中发现的畸形可能是由于胆固醇降低、7 DHC增加或这两种因素的组合。本文综述了SLOS的生理和行为表型，诊断方法，从产前到成年的自然史，以及目前对SLOS病理生理学的了解。(C)2012 Wiley Periodicals，Inc.
SmithLemliOpitz syndrome (SLOS) is a congenital multiple anomaly/intellectual disability syndrome caused by a deficiency of cholesterol synthesis resulting from a deficiency of 7-dehydrocholesterol (7DHC) reductase encoded by DHCR7. SLOS is inherited in an autosomal recessive pattern. It is characterized by prenatal and postnatal growth retardation, microcephaly, a variable degree of intellectual disability that encompasses normal intelligence to severe intellectual deficiency, and multiple major and minor malformations. External malformations include distinctive facial features, cleft palate, postaxial polydactyly, 23 syndactyly of the toes, and underdeveloped external genitalia in males, while internal anomalies may affect every organ system. The clinical spectrum is wide, and rare individuals have been described with normal development and only minor malformations. The clinical diagnosis of SLOS is confirmed by demonstrating an abnormally elevated concentration of the cholesterol precursor, 7DHC, in serum or other tissues, or by the presence of two DHCR7 mutations. The enzymatic deficiency results in decreased cholesterol and increased 7DHC levels, both during embryonic development and after birth. The malformations found in SLOS may result from decreased cholesterol, increased 7DHC or a combination of these two factors. This review discusses the physical and behavioral phenotype of SLOS, the diagnostic approaches, the natural history from the prenatal period to adulthood, and current understanding of the pathophysiology of SLOS. (C) 2012 Wiley Periodicals, Inc.