Introduction: Aromatase deficiency leading to virilization in mother and female fetuses during pregnancy is a rare disease. It is characterized by impaired estrogen production, increased gonadotropins, and ovarian cysts. Herein, we report a clinical phenotype of the virilized female due to a novel compound heterozygous mutation in CYP19A1.
Case report: A 4-month-old girl was referred due to cliteromegaly. Her mother had developed acne, hair loss, voice change, and hirsutism during pregnancy. She was born with a birthweight of 2710 gr at the 35th week of gestation. Her clitoris size had regressed after birth. The parents were no relatives. The physical examination revealed that her weight was 6.8 kg (0.36 SDS), length was 64 cm (0.48 SDS), a clitoral length of 1 cm, and posteriorly fused labia minora. Initial evaluations excluded congenital adrenal hyperplasia. Ultrasonography revealed a normal uterus and but no ovarian tissue. Gonadotropin levels were normal at the time of admission but increased by the age of 6 months (Table 1). Karyotype was identified as 46, XX and SRY was negative. The laparoscopic evaluation showed normal uterus and ovaries. The biopsy specimens from both gonads were histologically consistent with ovarian tissue and the karyotype analysis of this specimens revealed 46,XX. The diagnosis of aromatase deficiency was suspected and a previously unidentified compound heterozygote mutation in CYP19A1 [IVS10+1 G> A; p.R115Q (c.344 G> A)] was found. The parents were carriers. The in silico analyzes categorized the variant to be pathogenic. During the follow-up, the fusion at the posterior of the labium minus was surgically corrected and no ovarian cyst was observed with pelvic ultrasonography until now.
|16 days||4 months||6 months||8 months||11 months||17 months|
|Total testosterone (ng/dl)||78||<10||<10||-||-||-|
Conclusions: Aromatase deficiency should also be considered even if the initial FSH and LH levels are normal and ovarian cysts are lacking.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology