Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome

Abstract

The behavior phenotype of Smith-Lemli-Opitz syndrome (SLOS) was studied by assessing behavior, social, and communication abilities, sensory hyperreactivity, and the deficits associated with autistic disorder. Fifty-six SLOS subjects, age 0.3 to 32.3 years, were evaluated by multiple age-dependent questionnaires and telephone interviews. Of the 56 subjects, 50 (89%) had a history of repeated self-injury: 30 (54%) bit themselves; 27 (48%) head-banged; and 30 (54%) threw themselves backward in a highly characteristic upper body movement ("opisthokinesis"). Forty-seven of these subjects were also evaluated by direct observation and by direct interview of the parent or caregiver. Of 11 subjects 10 years or older, three (27%) had a stereotypic stretching motion of the upper body accompanied by hand flicking. Additional measures showed sensory hyperreactivity, temperament dysregulation, sleep disturbance, and social and communication deficits. Nine of 17 subjects (53%) met the diagnostic criteria for autistic disorder by the Autism Diagnostic Interview-Revised (ADI-R) algorithm questions [Lord et al., 1993, 1994]. Thus, SLOS is a metabolic disorder that can be associated with autism and other behavioral characteristics that define a distinctive and diagnostically important behavioral disorder.

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…The incidence has been estimated to be one in 10 000 to one in 60 000. 65 SLO can be improved by supplementary dietarial cholesterol. The phenotype is variable with only rare symptoms or multiple congenital anomalies comprising cleft palate, cataracts, ptosis, hypospadias, syndactyly and a distinctive craniofacial appearance.…”

“…66 The most common malformation in large-scale studies was the syndactyly of toes 2 and 3; however, only present in about 80% of affected individuals. 66,67 Two studies have shown a high rate of AD in individuals with SLO, 65,68 especially in children with a start of cholesterol supplementation after age 5 years.…”

Advances in behavioral genetics: mouse models of autism

“…[282][283][284] Interestingly, SLOS is a neurodevelopmental disorder characterized by high rates of autism. 285,286 The disease is caused by mutations in DHCR7, leading to a disruption in cholesterol synthesis and an accumulation of precursor sterols. 287 In mice, the loss of Dhcr7 function results in severe respiratory impairment, failure to feed, and death soon after birth.…”

Abnormalities of cholesterol metabolism in autism spectrum disorders

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AbstractAlthough Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al, 2001], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated 1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and 2) the type and incidence of other sterol disorders in the same group.

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“…Most SLOS individuals who survive the newborn period are compound heterozygotes for a common DHCR7 null mutation and a milder missense mutation, whereas the most mildly affected SLOS individuals carry two missense alleles with residual DHCR7 activity. Various genetic disorders such as fragile X syndrome, Joubert syndrome, Prader-Willi syndrome, tuberous sclerosis, and Down syndrome may present with autism spectrum disorders [Folstein and Piven, 1991].Individuals with SLOS children have a high incidence of autism [Tierney et al, 2001]. Among 17 patients with SLOS administered the algorithm questions of the Autism Diagnostic Interview-Revised (ADI-R; Lord et al, 1994), 53% met criteria for autism.…”