Case report and literature review: a 46,xx infant with atypical genitalia diagnosed with primary ovarian insufficiency (POI) caused by hfm1 gene variants

Zheng Yuan; Ming Cheng; Xi Meng; Bingyan Cao; Chunxiu Gong

doi:10.1530/endoabs.110.EP1374

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Endocrine Abstracts (2025) 110 EP1374 | DOI: 10.1530/endoabs.110.EP1374

ECEESPE2025 ePoster Presentations Reproductive and Developmental Endocrinology (128 abstracts)

Case report and literature review: a 46,xx infant with atypical genitalia diagnosed with primary ovarian insufficiency (POI) caused by hfm1 gene variants

Zheng Yuan ¹ , Ming Cheng ¹ , Xi Meng ¹ , Bingyan Cao ² & Chunxiu Gong ¹

Author affiliations

¹Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, China; ²Capital Institute of Pediatrics, Beijing, China

JOINT1075

Introduction: Primary Ovarian Insufficiency (POI) due to single gene variant is classified as a 46,XX difference of sexual development. Variants in the Helicase Family Member 1 (HFM1) gene are associated with POI in females and non-obstructive azoospermia in males.

Case Report: We described a case of POI with unique genital characteristics, including clitoromegaly, fusion of the labia majora, an opening of the urethral meatus at the perineum, and the absence of the vaginal opening. Hormonal analysis revealed hypergonadotropic hypogonadism. Genetic testing identified two variants in the HFM1 gene: c.1978-2A>C and c.2681-3T>A. A comprehensive analysis of published cases with HFM1 gene variations was conducted to summarize the range of variants and phenotypes associated with HFM1 gene mutations.

Discussion: This study connects HFM1 gene variants to external genital malformations, expanding the spectrum of phenotypes related to HFM1 mutations. Clinicians should consider the possibility of POI in 46 XX female infants with atypical genitalia and perform genetic testing for HFM1 to avoid overlooking the diagnosis.