Brain magnetic resonance imaging findings in smith–lemli–opitz syndrome

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27M, 28F) between age 0.17 years and 25.4 years (mean = 6.2, SD = 5.8) received a total of 173 brain MRI scans (mean = 3.1 per subject) on a 1.5T GE scanner between September, 1998 and December, 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and Type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS.

Normal IQ is possible in Smith‐Lemli‐Opitz syndrome

“…Thus, severity of cholesterol depletion in the brain is expected to affect the degree of neuronal dysfunction and somatic malformations including brain abnormalities such as microcephaly, holoprosencephaly, and corpus callosum agenesis. In support of this, Lee, Conley, Gropman, Porter, and Baker (2013) found significant correlations between brain anomaly severity score and other measures of SLOS severity such as somatic severity score, 7-DHC and total cholesterol levels. Lee, Yoshida, et al (2013) measured midsagittal corpus callosum (CC) length and area in individuals with SLOS and mild to severe developmental delay, and found that shorter CC length and smaller area correlated with lower developmental quotient in gross motor and language domains.…”

Decreased cerebral spinal fluid neurotransmitter levels in Smith‐Lemli‐Opitz syndrome

“…Congenital anomalies of the central nervous system include microcephaly in most individuals, as well as defects of myelination, malformations of the corpus callosum, abnormalities of the cerebellum including Dandy-Walker variant, and at the severe end of the spectrum, holoprosencephaly (Ryan, Bartlett et al 1998; Kelley and Hennekam 2000; Caruso, Poussaint et al 2004; Lee, Conley et al 2013; Lee, Yoshida et al 2013). Hypotonia is extremely common in infants and young children with SLOS, whereas older children often exhibit hypertonia.…”

Pathogenesis, epidemiology, diagnosis and clinical aspects of Smith–Lemli–Opitz syndrome

“…Strabismus is not uncommon. Imaging of the central nervous system often shows malformations, which range from septum pellucidum abnormalities and agenesis of the corpus callosum to holoprosencephaly in severe cases [26,27]. …”