Smith-Lemli-Opitz syndorme (SLOS) is an autosomal recessive disorder characterized by defective synthesis of cholesterol. It is estimated to affect one in 20,000 to 40,000 births. One of the key enzymes involved in cholesterol biosynthesis is defective in this disease, resulting in lack of cholesterol and accumulation of the cholesterol precursor, 7-dehydrocholesterol (DHC7). Since cholesterol is a major component of cell membranes and myelin sheath, and is also the precursor for steroid hormones and bile, as well as an important factor for proper embryonic development, its absence leads to several problems. The toxic accumulation of the 7-dehydrocholesterol precursor also leads to additional complications. Typical symptoms of SLOS are microcephaly, distinctive facial features characterized by broad nose, small lower jaw, cleft palate, and low set ears, hypotonia, toe-webbing, mental and growth retardation, and genital malformations. Affected individuals may also show malformations of the heart, kidney, lungs, or the gastrointestinal tract. According to the symptoms, SLOS has been classified as Type-I (characterized by mental retardation, and minimal anomalies), intermediate Type II, and Type III (characterized by major structural defects, and early lethality). The congenital malformations are mostly due to defects in morphogenesis during embryonal life, mediated by the lack of cholesterol.
Afifi et al, 2000, reported the first Egyptian cases with SLOS. They studied seven male patients (aged from 18 months to 18 years), and found the most common manifestations to be mental retardation, toe syndactyly, genital anomalies, micrognathia, and high arched palate. Other anomalies seen were microcephaly, hypotonia, and whorled fingertip pattern. The authors opined that SLOS was an under-estimated metabolic disorder and that the absence of reports of the disease from Egypt could be due to its extremely wide phenotypic spectrum.
[Afifi HH, Youssef SM, el Bassyouni HT. Clinical and biochemical variability of the classical Smith-Lemli-Opitz Syndrome in Egyptians. Ain Shams Med J. 2000; 51(4-6):421-433.]
Sawardekar, 2005, conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in an Omani hospital in Nizwa. Of the 21,988 total births in the hospital, one child was born with Smith-Lemli-Opitz Syndrome. The author hinted at a possible genetic contribution in this child.