ESPE Abstracts

Background: Disorder of sex development (DSD) includes a wide spectrum of clinical disorders affecting gonadal and genital development. Many causative gene mutations are involved in these disorders. One of these genes is nuclear receptor subfamily 5 group A member 1 (NR5A1) encoding Steroidogenic factor-1 (SF-1) located on chr 9q33.3. This gene is expressed in many tissues such as Sertoli cell and Leydig cell in testes, ovaries, placenta, adrenal cortex, hypothalamus and anterior pituitary taking part in the regulation of their functions. There are lots of detected mutations in this gene those can cause a variety of phenotypic features in patients with XY DSD.

Objectives: This study describes a spectrum of phenotypic features of four patients with XY DSD who have different mutations in NR5A1 gene.

Cases description: It is a case series of four patients with XY DSD having different heterozygous mutations in NR5A1 gene. Two patients were presented at birth by ambiguous genitalia. No internal female genitalia were found. One of them had extra-genital manifestations such as arrested hydrocephalus, renal anomalies, ear tag, short stature and learning disabilities. This patient had spontaneous virilization at puberty. The third patient was normal baby girl at birth and reared as a female. Then, spontaneous virilization of external genitalia occurred at pubertal age with no breast maturation. This patient had increased hair distribution in extremities, abdomen and chest at pubertal age. He had no internal female genitals. The fourth one was presented by cliteromegaly, but she was reared as a female till puberty. This patient had no internal female genitals, normal hair distribution and no breast development. The first two patients were assigned as males and the remaining patients were assigned as females and received tapered feminizing hormonal treatment as an induction of puberty. All of them had normal adrenal function. Furthermore, testicular function was evaluated in all patients. the karyotype was 46,XY for all patients. The syndromic one had additional mutation in FRAS1 gene besides NR5A1 mutation which might cause the associated renal manifestations. additionally, the last two patients had the same NR5A1 novel mutation.

Conclusion: Although, NR5A1 gene mutation is a common cause of XY DSD, it has a wide spectrum of phenotypic features. This may be due to different mutations in the same gene or due to associated gene mutations.