Spontaneously regressing brain lesions in Smith-Lemli-Opitz syndrome

Dang Do AN, Baker EH, Warren KE, Bianconi SE, Porter FD. Spontaneously regressing brain lesions in Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2018 Feb;176(2):386-390.

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn error of cholesterol synthesis that affects the development of many organ systems. Malformations in the central nervous system typically involve midline structures and reflect abnormal growth and differentiation of neurons and supporting cells. Despite these defects in central nervous system development, brain tumor formation has only rarely been reported in association with SLOS. We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals' clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions.

This is a series of T2-weighted images of Individual 2. At age 3 years 3 months no lesion is visible. At age 5 years 10 months, the lesion measures 12 mm and is slightly exophytic. At age 7 years 7 months, the lesion remains exophytic and measures its maximum size of 16 mm. At age 16 years 9 months, the lesion is no longer visible, but the left anterior pons remains expanded.