SMITH LEMLI OPITZ SYNDROME

SLO Syndrome; SLOS; RSH Syndrome; DHCR7 Deficiency; Smith-Lemli-Optiz Syndrome Type II

Smith Lemli Opitz Syndrome (SLOS) is an inherited genetic disorder that results in an enzyme deficiency (7-dehydrocholesterol reductase, or 7-DHC reductase) necessary for cholesterol metabolism. Toxic byproducts of disrupted cholesterol synthesis build up in the blood, nervous system, and other tissues, disrupting the growth and development of many body systems. SLOS is characterized by multiple congenital malformations that are so severe that the fetus is often miscarried or still-born, or the infant dies within the first weeks of life. Surviving infants have dysmorphic facial features, microcephaly, toe abnormalities, and developmental delay. Many affected children have features of autism, and physical malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia. Feeding difficulties and failure to thrive are common. Vision loss due to cataracts and optic nerve abnormalities, and hearing loss may also occur.

Diagnostic testing: A definitive diagnosis of SLOS is by the measurement of plasma sterols, including cholesterol and genetic testing for evidence of mutations in the DHCR7 gene.

Physical findings:

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  Microcephaly;

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  Characteristic facial features such as broad nose, small lower jaw, and low set ears; and

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  Hypotonia (floppy muscle tone).

These infants may also have:

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  Webbing of the second and third toes (syndactyly);

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  Extra fingers or toes (polydactyly);

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  Cleft palate;

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  Heart and lung defects;

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  Brain malformations; and

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  Hearing loss.

ICD-9: 272.8

SLOS is a genetic condition that is present prior to birth but has signs that are so subtle that detection is not made until later childhood. Most cases identified at birth or shortly after birth are due to obvious birth defects. Mildly affected individuals may have only minor physical abnormalities with learning and behavior problems Some children with SLOS may have more severe intellectual impairments, multi-organ system failure, and behavior problems that can include antisocial, self-destructive, or violent acts; or withdrawal, self-stimulation, and autism.

There is no current cure for SLOS. Treatment is supportive and may include surgery to repair physical conditions, such as heart defects, cleft palate, or foot deformities. Hearing aids may benefit those with hearing loss. Gastrostomy feeding may be necessary for nutritional needs.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical history and examination that describes diagnostic features of the impairment;

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  Laboratory findings;

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  Imaging studies of affected organs (brain, kidneys, heart, or lungs); and

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  Psychological testing with evidence of intellectual impairment.

Suggested Listings for Evaluation:

REMARKS