ESPE Abstracts

Introduction: Primary ovarian failure (POF) is traditionally defined as cessation of menstruation prior to 40 yr of age and diagnosis is confirmed by elevated serum FSH levels (often above 40 IU/L). It is known that 0.1% of the population is affected with POF before age 30 yr. Here, we report a case with POF, who presented wit tall stature due to structural abnormalities in X chromosome.

Case Report: A 13.5 year-old-adolescent girl was brought to medical attention because of secondary amenorrhea. She was born at term without any perinatal problems. The parents were second- degree cousins. Past medical history was unremarkable. She was 177 cm (2.9 SDS) tall. Her body mass index was 23.3kg/m2 (1.01SDS). Her midparental height was 171 cm (1.35 SDS). The physical examination revealed normal findings except for kyphoscoliosis. There were no other pathologic findings. Her Sexual Maturity Rating was consistent with Stage 3. Laboratory work up showed that serum LH and FSH levels were 25 mIU/ml and 43.7 mIU/ml, respectively. Serum estradiol level was 35.8 pg/ml and AMH level was <0.01 ng/mL. Serum androstenedione, dehydoepiandrosterone-sulfate, testosterone, 17-hydroxyprogesterone, prolactin levels and thyroid function tests were all normal. Due to tall stature, GH-IGF axis was evaluated; serum IGF-1 level was also normal, 304µg/l (SDS: -0.44). Pelvic ultrasonography showed uterine hypoplasia and streak ovaries. The karyotype was 46,XX. Due to coexistence of tall stature and POF, chrosomal microarray was performed. Partial Xq deletion and partial Xp duplication including SHOX gene was identified [(Xp22.33p11.21 (265492_57830778)x3, Xq22.2q28 (103534396_156003212)x1)]. She was placed on sex steroid replacement therapy with the diagnosis of POF.

Conclusion: Here, we report a case of POF who presented with tall stature due to SHOX overdosage. Gene dosage alterations in X chromosome that require molecular genetic tests should be considered in POF patients with tall stature that is unexplained by parental stature. A structurally abnormal X chromosome with Xp duplication concomitant with partial Xq deletion is a rare event. In the few cases reported to date, a very tall stature has been a frequent clinical finding. The enhancing effect of SHOX gene triplication in combination with estrogen deficiency has been proposed as a factor leading to tall stature.