ESPE Abstracts

Background: We present a 17-year-old female who presented with a 1 year history of hirsutism, male pattern baldness, marked cystic acne and mild cliteromegaly. She had her menarche at the age of 15 years and continued thereon to have a regular menstrual cycle. She was pubertal on examination (B3, P5, A5) with no neurological deficit.

Objective and hypotheses: This female presented with marked clinical hyperandrogenism. We initially suspected polycystic ovarian syndrome (PCOS) given her phenotype. Through investigation and characterisation she has been found to have an unusual genetic mutation which we hypothesise is causative of her symptoms.

Method: Our case had blood taken for baseline endocrinology, genetic testing, provocation testing, 24 h urine for steroid profiling, and an ultrasound scan of her abdomen/pelvis. She was commenced on treatment for PCOS with Yasmin which she has not shown an early response to.

Results: She was found to have a normal pubertal ultrasound scan, normal baseline endocrinology, normal provocation testing and a normal 24 hour urinary steroid profile. Her microarray revealed she carries a 46XX/47XX+ mosaic karyotype with a supernumerary marker chromosome which was shown to be derived from the long arm of the X chromosome. This additional genetic material contains the androgen receptor gene but does not include the XIST gene and therefore genes present in this marker chromosome would not be subject to x-inactivation. This was found to be a de novo mutation.

Conclusion: We present a novel case of a de novo genetic mutation that we hypothesise has led to overexpression of the androgen receptor leading to her having increased sensitivity to normal levels of circulating androgens. The resulting severe phenotype mimics PCOS in appearance but with normal blood biochemistry, urinary steroid profile and ultrasound.