Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome

Abstract

Case series

Patients: 38, female • 28, female • 41, female • 18, female • 23, male

Final Diagnosis: Woodhouse-Sakati syndrome

Symptoms: Hypogonadism • dystonia • alopecia • hearing loss • diabetes

Medication: —

Clinical Procedure: —

Specialty: Endocrinology and Metabolic

Objective:

Rare disease

Background:

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic condition that was first described in 1983. Since its original description, approximately 50 cases have been reported with various clinical signs and symptoms. Characteristics include progressive neurologic deterioration with extrapyramidal involvement and polyendocrinopathy most notable for hypogonadism starting in early adolescence. Clinical presentation is variable, and a subset of patients may have additional features, such as premature aging, alopecia, distinctive facial features, cognitive impairment, or deafness.

Case Report:

We illustrate the phenotypic variability of 5 patients with WSS due to the previously reported homozygous single nucleotide deletion c.436delC in the DCAF17 gene, identified in 2008. Despite identical genetic alteration, our 5 patients had various clinical features among them and compared with previously reported cases with the same pathogenic mutation.

Conclusions:

The phenotypic variability of WSS due to c.436delC founder mutation may have a wider range than previously recognized.