Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz Syndrome (SLOS)
By: Suraj Gathani

Description and Occurrence
* Autosomal recessive disorder
o Cholesterol metabolism effected.
* Common characteristics:
o Multiple malformations at birth.
o Mental retardation later.
* Occurrence:
o 1 in 20,000 people of central European decedents.
o Rare in Africans and Asians.

Clinical Features
* Clinical anomalies:
o Mental retardation (100% affected)
o Small brain at birth (microcephaly) >90%
o Second and third toe fusion (synadactyly) ~98%
o Genital abnormalities in males >50%
o Muscle weakness (hypotonia) ~50%
o Polydactyly
o Abnormalities of heart, lung, kidneys, and liver.

Smith-Lemli-Opitz Syndrome
* Distinctive facial features:
o High, broad forehead
o Narrow temples
o Upward pointing nostrils
o Drooping eyelids and a broad nasal bridge
* Behavioral characteristics:
o Repeated self injury
o Prolonged temper tantrums & violent outbursts
o Hyperactivity

Molecular Defects
* Caused from mutation in the DHCR7 gene
o Located at 11q12-13
o Encodes for sterol-Δ7-reductase
* Defects in sterol-Δ7-reductase
o Build up of 7-dehydrocholesterol
o Deficiency of cholesterol
* Importance of cholesterol
o Important component in cell membrane and myelin sheaths
o Precursor for steroid hormones such as progesterone
o Precursor for bile salts

Cholesterol Metabolism
Diagnosis and Treatment
* Diagnosis:
o Detection of an elevated level of 7-dehydrocholesterol in plasma
* Treatment:
o Individuals with SLOS need support and care
o Congenital abnormalities can be corrected with surgery.
o Dietary cholesterol supplementation is beneficial.

Reference

Smith-Lemli-Opitz Syndrome.ppt