SAT-297 Mutation in SRY Gene Presenting as Syndromic 46XY Disorder of Sexual Differentiation (DSD)

Introduction Mutations in the SRY gene presenting as sex reversal is rare and not associated with problems in other organ systems. We report a case of a 46 XY adolescent with history of cleft lip and palate, phenotypically female, diagnosed with a mutation in the SRY gene causing sex reversal. Clinical Case A 14 year old phenotypically female patient was referred to our Endocrine clinic for evaluation of delayed puberty. She reported body odor for one year, without breast development, axillary or pubic hair. The family reported normal growth pattern growing at about 2 inches per year. She had a history of cleft lip and palate that had been repaired during infancy. They reported a history of recurrent 4-5 urinary tract infections in her lifetime. Her mother reported menarche at 12 years age, while her father had slightly delayed puberty. On physical examination her height was at z-score -0.63, weight z-score 0.42, BMI z-score 0.74. She had healed surgical scars on her right lip, with no other dysmorphic features. She had Tanner stage I breasts and no pubic or axillary hair. Examination of the external genitalia showed a normal vaginal and urethral opening with no clitoromegaly. Laboratory testing was significant for hypergonadotropic hypogonadism. Bone age was 10 years, therefore significantly delayed. Pelvic ultrasound showed a pre-pubertal uterus measuring 1.9 x 0.3 x 1.0 cm. The right gonad measured 1.5 x 1.0 x 1.1 cm. The left gonad was not visualized and there was no adnexal mass. MRI of the pelvis showed a prepubertal uterus measuring approximately 2 x 1 x 0.4 cm, and possible gonadal tissue measuring 1.2 cm on the left and 1.1 cm on the right, located antero-medial to the external iliac vessels. The urinary bladder was normal. Chromosomal analysis was consistent with 46,XY, ish(Y)(SRY+). Laparoscopic bilateral gonadectomy was performed without any complications. There was no indentifiable gonad on the right side but a formed fallopian tube with fimbria and an adjacent mesonephric duct remnant was identified. On the left side a small dysgenetic gonad with ovarian stroma, müllerian ductal epithelial remnant, ovarian hilar cell nests without germ cells, were identified. Genetic testing was done and was significant for a variant c.380A>G (p.Tyr127Cys), identified in her SRY gene. She was subsequently started on Estrogen supplement to which she is responding well. Conclusion - Mutations in the SRY gene presenting as sex reversal is rare and not reported to be associated with problems in other organ systems. Our patient with 46 XY sex reversal due to SRY mutation, had a history of cleft lip and palate, which has not been reported before to our knowledge. - Variants that disrupt the p.Tyr127Cys amino acid residue in SRYgene has been observed in affected individuals.