Smith-Lemli-Opitz Syndrome (SLOS) Suraj Gathani

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

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

Smith-Lemli-Opitz Syndrome Distinctive facial features: –High, broad forehead –Narrow temples –Upward pointing nostrils –Drooping eyelids and a broad nasal bridge Behavioral characteristics: –Repeated self injury –Prolonged temper tantrums & violent outbursts –Hyperactivity images/grade5_small.jpg

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

Cholesterol Metabolism lemli-opitz_silva_jeanty_files/cholesterol-smith-1.gif

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

Reference Jira, P.E., Waterham, H.R., Wanders, R.J.A., Smeitink, J.A.M., Sengers, R.C.A.: Smith-Lemli-Opitz Syndrome and the DHCR7 Gene. Annals of Human Genetics. 2003;67, Pasternak, J.J.: An introduction to Human Molecular Genetics. Second Edition. Pg John Wiley & Sons Inc River Street, Hoboken, NJ images/grade5_small.jpg images/syndromes/smith-lemli- opitz_silva_jeanty_files/cholesterol-smith-1.gif