Recent insights into the Smith–Lemli–Opitz syndrome

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Abstract
The Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation disorder caused by an inborn error of post‐squalene cholesterol biosynthesis. Deficient cholesterol synthesis in SLOS is caused by inherited mutations of 3β‐hydroxysterol‐Δ7 reductase gene (DHCR7). DHCR7 deficiency impairs both cholesterol and desmosterol production, resulting in elevated 7DHC/8DHC levels, typically decreased cholesterol levels and, importantly, developmental dysmorphology. The discovery of SLOS has led to new questions regarding the role of the cholesterol biosynthesis pathway in human development. To date, a total of 121 different mutations have been identified in over 250 patients with SLOS who represent a continuum of clinical severity. Two genetic mouse models have been generated which recapitulate some of the developmental abnormalities of SLOS and have been useful in elucidating the pathogenesis. This mini review summarizes the recent insights into SLOS genetics, pathophysiology and potential therapeutic approaches for the treatment of SLOS.