Background: NR5A1 mutations in DSD patients result in a wide range of clinical manifestations.
Objective and hypotheses: To evaluate the clinical variability of ambiguous phenotypes and the gender assignment in DSD patients with SF1 mutations.
Method: Clinical examination, hormonal tests, ultrasound, laparoscopy and molecular analyses, including direct and parallel sequencing
Results: Case 1. A girl, aged 18 months with female phenotype and Prader II clitorophallus. A small testis was detected in the right labioscrotal fold. The karyotype was 46,XY. Hormonal tests showed LH 0.25 IU/l, FSH 12.9 IU/l and testosterone after hCG stimulation test 0.3 nmol/l. Pelvic ultrasound and laparoscopy showed the uterus, fallopian tubes and a dysgenetic abdominal gonad on the left side. Bilateral gonadal disgenesis was diagnosed. Molecular analyses detected the nonsense mutation c.256delA of NR5A1. Case 2. A boy, aged 5 months, with ambiguous genitalia. The left testis was found in labioscrotal fold and the right testis was not palpable. The patient had perineal hypospadias and a small phallus 1.5 cm. Hormonal tests showed testosterone 5.6 nmol/l, LH 2.2 IU/l, FSH 5.0 IU/l and AMH 43.8 ng/ml. Pelvic ultrasound detected no uterus and found urogenital sinus. As a result of examination, 5ARD2 deficiency was supposed. However, it was not proved by molecular analyses. The following test revealed the heterozygous p.R313C mutation of NR5A1. Case 3. A 46,XY boy, aged 16 month with similar phenotype was examined. Small testes were palpable in bifid scrotum. Uterus not found during pelvic ultrasound. Heterozygous p.S303R mutation of NR5A1 was detected.
Conctusion: Clinical manifestation of DSD caused by SF1 mutations are characterized by phenotype variability.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology