Background: 46,XX gonadal dysgenesis is a rare condition linked to delayed puberty, absence of spontaneous pubertal development, and primary amenorrhea related to hypergonadotropic hypogonadism (Hh). External genitalia are typically female with no ambiguity. Although ovarian development is an active process with multiple gene involvement, the genetic etiology of this condition is usually unknown. DCAF17 has recently been implicated in the development of both male and female gonads, thus resulting in hypogonadism. This condition represents one component of Woodhouse-Sakati syndrome (WSS), arising from mutations in the DCAF17 gene, an extremely unusual autosomal recessive disorder.
Methods: A 16-year-old girl with consanguineous parents presented due to delayed puberty, absence of spontaneous pubertal development, and primary amenorrhea. Hypogonadism was present, in the form of Hh. Whole-exome sequencing was used to identify the genetic etiology underlying the hypogonadism.
Results: A novel homozygous variant c.1091+1G>A was detected in DCAF17. Both parents were sequenced and identified as heterozygous for the same mutation.
Conclusions: Various manifestations of WSS do not emerge until later in life, making diagnosis in pediatric cases particularly difficult, as in the present report. DCAF17 may also be implicated in the genetic etiology of 46,XX gonadal dysgenesis.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology