ESPE Abstracts

The SRD5A2 gene (MIM607306) codes for the type 2 5α-reductase enzyme that catalyzes the conversion of testosterone to its active metabolite, dihydrotestosterone (DHT), essential for the development of the male external genitalia. Pathogenic variants in homozygosis or compound heterozygosis may be responsible for a 46XY Disorder of Sex Development.

Case: A 5-year-old girl who was referred to us after the mother noticed lumps on both labia majora when adopting the genuflecting position. No family or personal history of interest, clinical examinations at birth record genital examination at birth and in successive health check-ups as a normal-configured female phenotype. - Clinical examination: 5.2 years old, 19.5 kg (p45, +0.1 SD), 115cm (p72, +0.61 SD), BMI: 14.7 kg/m2 (p31, -0.2SD), female phenotype. Rounded masses in the bilateral inguinal area, close to the pubis measuring 1.5 x 1.5 cm, cremasteric reflex detectable in genuflection. Thickened labia majora, labia minora decreased in size with posterior fusion, vaginal introitus, normal-shaped non-hypertrophic clitoris. Prader 3/5. - Abdominal ultrasound: testes are observed in the inguinal canal, 13x4 mm and 12x4mm, epididymis is identified. There is no evidence of the uterus or ovaries. - Abdominal MRI: normal-sized testes with epididymis and minimal amount of fluid around them are observed in the inguinal canal. No ovary, uterus, or prostate is identified. In the labia majora, a small vaginal introitus can be sensed, without connection to any anatomical structure. - 46, XY karyotype. SRY gene positive. - Prepubertal gonadal profile with LH 0.12 mIU/ml, FSH 0.7 mIU/ml, Antimüllerian Hormone 107 ng/ml, Inhibin B 101 pg/ml. Estradiol <24 pg/ml, Prolactin 9.2 ng/ml, Cortisol 9 mg/dl.

- A homozygous variant was detected, c.377A>G; (p.Gln126Arg) in exon 2 of the SRD5A2 gene, already previously described as pathogenic; heterozygous parents (INGEMM, SDSeq_v3.0).

Conclusions: Genital feminization is a clinical challenge that requires a correct gender assignment, taking into account factors such as identity, the possibility of fertility, the need for masculinizing genitoplasty or gonadectomy and hormone replacement treatment, being of vital importance to have a multidisciplinary team.