(36) Estrogen Supplementation for Premature Ovarian Insufficiency Management in Adolescent with Mandibular Hypoplasia Deafness Progeroid Lipodystrophy Syndrome (MDPL)

Background: Mandibular hypoplasia deafness progeroid lipodystrophy syndrome (MDPL) is a rare autosomal dominant systemic disorder, which affects approximately 16 people worldwide. It is caused by mutations in the POLD1 gene, and is characterized by loss of subcutaneous fat, sensorineural deafness, along with metabolic abnormalities including diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Current literature has shown this condition to also be characterized by hypogonadism. Management of premature ovarian insufficiency with estrogen supplementation in patients with MDPL has yet to be studied.

Case: We present a 16-year-old female with MDPL. She was evaluated at 14 years old for delayed puberty. During evaluation, labs revealed elevated FSH levels, meeting criteria for premature ovarian insufficiency (POI). Patient was subsequently started on estradiol. Despite the dose of estrogen supplementation being increased over a 6-month period, there was minimal breast growth and concern for potential worsening of MDPL.

Comments: There have been 2 females reported with hypoplastic breast development. However, the current literature lacks thorough discussion of other aspects of puberty and secondary sexual characteristics in females with MDPL. Prior studies have only focused on the use of hormone replacement on solely males with this disorder. There has yet to be any cases that discuss estrogen supplementation in females with this disorder and potential effects.

This particular case illustrates the complexity associated with estrogen supplementation in patients given the potential impact on MDPL. There is also a need for further studies on exogenous estradiol supplementation in individuals with MDPL and expectations for development of secondary sexual characteristics.