Elias Ellen Roy
Pediatrics and Genetics, University of Colorado School of Medicine, Special Care Clinic, Children's Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, United States.
J Steroid Biochem Mol Biol. 2025 Nov;254:106822. doi: 10.1016/j.jsbmb.2025.106822. Epub 2025 Jul 1.
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive genetic disorder associated with complex anatomic abnormalities, accompanied by medical, developmental and behavioral challenges. It was the first human disorder identified to be caused by an error in the complex cholesterol biosynthetic pathway, more than thirty years ago. This review will cover the clinical and developmental phenotype of patients with SLOS, and the understanding of how cholesterol deficiency, accumulation of the cholesterol precursors 7- and 8-dehydrocholesterol (7-DHC and 8-DHC), and the oxidation of these precursors into toxic oxysterols, are now known to cause this complex phenotype. There is a wide range of severity in patients with SLOS. The most severely affected babies may be miscarried or die in the newborn period due to lethal congenital anomalies. The most mildly impacted patients may show few anatomic abnormalities other than 2-3 toe syndactyly, but still display cognitive and behavioral challenges along the autism spectrum. The review will also cover the medical evaluation and interventions which are recommended in caring for patients with SLOS. There is no cure for this devastating disease, but certain interventions can lead to an improved quality of life, and stabilization of progressive problems for these complex patients.
史密斯-勒米-奥皮茨综合征（SLOS）是一种常染色体隐性遗传疾病，与复杂的解剖学异常相关，同时伴有医学、发育和行为方面的问题。三十多年前，它是首个被确定由复杂胆固醇生物合成途径错误导致的人类疾病。本综述将涵盖SLOS患者的临床和发育表型，以及目前对胆固醇缺乏、胆固醇前体7-脱氢胆固醇和8-脱氢胆固醇（7-DHC和8-DHC）的积累，以及这些前体氧化为有毒氧化甾醇如何导致这种复杂表型的理解。SLOS患者的严重程度差异很大。受影响最严重的婴儿可能因致命的先天性异常而流产或在新生儿期死亡。受影响最轻的患者除了2-3趾并指外可能几乎没有解剖学异常，但仍会表现出自闭症谱系中的认知和行为问题。本综述还将涵盖在护理SLOS患者时推荐的医学评估和干预措施。这种毁灭性疾病无法治愈，但某些干预措施可以提高这些复杂患者的生活质量，并稳定其进行性问题。
