Smith-Lemli-Opitz Syndrome (SLOS)

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Smith-Lemli-Opitz Syndrome (SLOS)

• Suraj Gathani

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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.

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Clinical Features

• Clinical anomalies
• Mental retardation (100 affected)
• Small brain at birth (microcephaly) gt90
• Second and third toe fusion (synadactyly) 98
• Genital abnormalities in males gt50
• Muscle weakness (hypotonia) 50
• Polydactyly
• Abnormalities of heart, lung, kidneys, and liver.

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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
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Molecular Defects

• Caused from mutation in the DHCR7 gene
• Located at 11q12-13
• Encodes for sterol-?7-reductase
• Defects in sterol-?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

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Cholesterol Metabolism
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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.

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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. 200367,269-280
• 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/synd
  romes/smith-lemli-opitz_silva_jeanty_files/cholest
  erol-smith-1.gif