1. Smith-Lemli-Opitz Syndrome (SLOS) Suraj Gathani

2. 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.

3. 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.

4. 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 www.apollos.net/.../ images/grade5_small.jpg

5. 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

6. Cholesterol Metabolism http://www.thefetus.net/images/article-images/syndromes/smith- lemli-opitz_silva_jeanty_files/cholesterol-smith-1.gif

7. 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.

8. 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;67,269-280 Pasternak, J.J.: An introduction to Human Molecular Genetics. Second Edition. Pg. 550-552. John Wiley & Sons Inc. 2005. 111 River Street, Hoboken, NJ 07030. www.apollos.net/.../ images/grade5_small.jpg http://www.thefetus.net/images/article- images/syndromes/smith-lemli- opitz_silva_jeanty_files/cholesterol-smith-1.gif