Biochemical and genetic diagnosis of Smith-Lemli- Opitz syndrome in South Africa

Abstract

Background. The Smith-Lemli-Opitz syndrome (SLOS), due to defective function of 7-dehydrocholesterol reductase, is an autosomal recessive disorder that is more common than other defects in cholesterol biosynthesis. The dysmorphology can be suggestive, but biochemical and genetic investigations are required for confirmation of this diagnosis to assist with the management of the patient and planning for future children in affected families.
Objective. To perform biochemical and genetic work-ups in four South African families of European ancestry with suspected SLOS in a range of presentations, from early fatality, congenital malformations, feeding problems and developmental delay.
Methods. Plasma was analysed by ultraviolet spectrophotometry. The genetic cause was investigated by polymerase chain reaction, followed by high-resolution melting and sequencing of amplicons displaying abnormal patterns.
Results. Spectrophotometry confirmed the diagnosis in three families. Genetic confirmation was made in these patients, and carrier status confirmed in the parents of the fatal case. All the patients were of European ancestry, and the mutations reflected those in European studies.
Conclusion. This rare disorder should be considered in antenatal assessment when increased nuchal lucency is detected on sonography, or in newborns with syndactyly, hypotonia and feeding problems. Less severe forms could present with developmental delay and behavioural problems. Confirmation of the diagnosis may assist in decisions about nutritional management as well as future pregnancies in the affected family and primary relatives.