The girl was born full-term vaginally with birth weight 3.380kg. She had stayed in neonatal unit for 3 days for neonatal fever. Physical examination was unremarkable. She had normal-looking female external genitalia. She was discharged after a negative infection screen.
She presented again at the age of 11 years with hoarseness of voice. Physical examination revealed normal growth and blood pressure. She had hoarseness of voice with mild laryngeal prominence. She had no goitre and no hirsutism. Pubertal examination showed stage 1 breast, prominent phallus measured 3cm in length and 2cm in width, bilateral palpable gonads in inguinal regions and stage 3 pubic hair. Both labia majora and minora were seen. Urethral opening was seen but vaginal opening was not well seen. Other systemic review was unremarkable.
Extensive investigations were performed for her virilization. Karyotype was 46, XY. SRY gene was present with no mutation detected by Sanger sequencing. Biochemistry showed LH 33.1 IU/L, FSH 61.3 IU/L, oestradiol 26 pmol/L, testosterone 8.3 nmol/L, 17-hydroxyprogesterone 1.9 nmol/L, androstenedione 1.1 nmol/L, AMH 0.39 µg/L, AFP 2 µg/L and b-HCG <1 IU/L. USG scan showed normal adrenal glands, no urogenital anomalies, no uterus and ovary identified and both gonads in inguinal regions. MRI scan confirmed no uterus and ovary identified, bilateral undescended testes in inguinal regions and hypoplastic vagina.
Paediatric urologist and paediatric gynaecologist had been consulted. Examination under anaesthesia revealed right gonad at superficial inguinal pouch and left gonad inside inguinal canal. External genitalia favoured female phenotype with normal-looking labia majora and underdeveloped labia minora, separate urethral and vaginal openings at introitus, phallus enlarged measured 4cm in length and 1.6cm in width. Cystoscopy showed normal-looking female type urethra, normal bladder with bilateral ureteric orifices at orthotopic position. Vaginoscopy showed blind-ended vagina lined by normal-looking mucosa with length of 4cm, no cervical opening seen.
Whole exome sequencing revealed no mutation in SRD5A2 gene but a missense mutation c.2591T>A (p.Leu864Gln) in AR gene. This mutation has been found previously in a case of complete androgen insensitivity syndrome. The underlying pathology had been explained to the parents and the girl. The gender options and subsequent management had been counselled. GnRH analogue was offered for adequate time for decision making and defer of surgery during school holiday. 5 months after the treatment, hoarseness of voice improved, and phallus reduced to 3cm in length and 1.3cm in width.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology