Clinical and Molecular Findings in Two Siblings with a Novel Homozygous DCAF17 Frameshift Variant and Review of the Literature: A Case Report.

INTRODUCTION: Woodhouse-Sakati syndrome (WSS) is an ultra-rare autosomal recessive multisystem disorder caused by biallelic pathogenic variants in DCAF17. The condition is characterized by endocrine dysfunction, ectodermal abnormalities, and variable neurological involvement, with considerable intra- and inter-familial phenotypic heterogeneity. CASE PRESENTATION: We report two siblings born to consanguineous parents who presented with short stature, delayed puberty, partial alopecia, and hypogonadism. The male sibling had hypogonadotropic hypogonadism and intermittent hyperglycemia, while the female sibling showed delayed pubertal development with bilaterally atrophic ovaries. Brain magnetic resonance imaging demonstrated iron accumulation in the globus pallidus in both patients, without overt extrapyramidal symptoms. Molecular analysis identified a novel homozygous frameshift variant in exon 13 of DCAF17 (NM_025000.4: c.1382_1383del; p.Thr461Ilefs*3), predicted to cause loss of function and classified as pathogenic according to ACMG/AMP criteria; segregation analysis confirmed parental heterozygosity. CONCLUSION: Although a definitive genotype-phenotype correlation for DCAF17 has yet to be established, the phenotypic overlap between our patients and previously reported cases supports the clinical consistency of WSS. The observation of persistent erythrocyturia and hemoglobinuria in both siblings represents an additional clinical finding; however, its relationship to WSS remains uncertain and requires further investigation. The identification of this novel pathogenic DCAF17 variant further broadens the mutational spectrum of the disorder.