A clinical and molecular investigation of two South African families with Simpson-Golabi-Behmel syndrome.

Background: Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked recessive overgrowth syndrome manifesting primarily in boys and characterised by macrosomia, distinctive facial features and multiple congenital abnormalities. Although this rare condition is thought to be underdiagnosed, making a diagnosis is important as affected boys have a 7.5% risk of developing visceral tumours and surveillance is warranted. Mutations in GPC3 are found in up to 70% of boys affected with SGBS.

Objectives: A clinical and molecular investigation of two boys with SGBS, probands B and S, and their mothers. Documentation of the clinical phenotype could assist with diagnosis in affected boys and will lead to early initiation of tumour surveillance.

Methods: Hospital folders were reviewed and clinical consultations arranged for both probands and their mothers. Molecular investigations initially searched for whole-exon deletions in GPC3 followed by gene sequencing.

Results: The clinical phenotype of both probands was consistent with that previously reported in the literature. The main features pointing towards the diagnosis were macrosomia, coarse facial features and macroglossia with a midline groove in the tongue. Proband B developed a Wilms tumour. He was found to have a novel mutation causing a premature stop codon.

Conclusions: This research represents the first published report of SGBS in South Africa. Early recognition and confirmation of this condition is important in order to institute tumour surveillance and assist families with accurate recurrence risks.