SMITH-LEMLI-OPITZ SYNDROME

• Autosomal recessive inheritance.
• Reduced cholesterol synthesis and accumulation of the cholesterol precursor 7-dehydrocholesterol (probably due to a deficiency of the enzyme 7-dehydrocholesterol reductase (1).
• A wide phenotypic spectrum for the same biochemical defect is described, but there is debate whether the severity of the biochemical defect correlates with the phenotype.

1. Hypospadias.
2. Syndactyly of the toes.
3. Postaxial polydactyly.
4. Club foot.
5. Microcephaly.
6. Mental retardation.
7. Cleft palate.
8. Cardiac defects.
9. Abnormal lung lobulation.
10. Ambiguous or female external genitalia in the male.
11. Increased nuchal translucency in the first trimester (2). Progression to second trimester nuchal edema and third trimester fetal hydrops has been reported (3).
12. Hirschprung's disease.
13. Renal dysplasia.

RECURRENCE RATE

Sib recurrence rate is less than one would expect (18%).
There is an increased number of miscarriages in sibships.

REFERENCES

1. Tint GS, Irons M, Elias ER et.al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994;330:107-113.
2. Hobbins JC, Jones OW, Gottesfeld S et.al. Transvaginal sonography and transabdominal embryoscopy in the first trimester diagnosis of the Smith-Lemli-Opitz syndrome, type 2. Am J Obstet Gynecol 1994'171:546-549.
3. Ogle RF, Maymon R, Chitty LS. Smith-Lemli-Opitz presenting nuchal edema and non-immune hydrops. World Congress in Ultrasound in Obstetrics and Gynecology. Poster Presentation. Edinburugh, November 1998.