ESPE Abstracts

Background: Wiedemann–Steiner syndrome (WSS) is a rare autosomal dominant disorder characterized with hypertrichosis cubiti, dysmorphic facial appearance (hypertelorism, thick eyebrows, and narrow palpebral fissures), psychomotor delay, and short stature. WSS is caused by a mutation in the KMT2A gene. The timing of secondary sexual characteristics in patients with WSS is not well known. To our knowledge, two patients (one boy and one girl) with WSS have been reported to have had central precocious puberty (CPP). It has been reported that 20–47% of patients with WSS showed advanced bone age; however, signs of secondary sexual characteristics in these cases were merely mentioned. Therefore, some of the cases with advanced bone age in these reports might have had CPP, although the first reported patient with WSS who showed advanced bone age did not show signs of secondary sexual characteristics.

Case presentation: A female patient was born at 39 weeks of gestation with a weight, height, and head circumference at birth of 2712 g (+0.15 SD), 47.5 cm (-0.69 SD), and 29.0 cm (-3.06 SD), respectively. She has had hypertrichosis on her arms and legs since birth. She showed hypertelorism, narrow palpebral fissures, and arched and thick eyebrows. Her psychomotor development was delayed with head support obtained at 7 months, and she was able to sit stably at 10 months, walk independently at 3 years, and speak her first words at 5 years. She was referred to our endocrinology outpatient clinic at 9.3 years of age with a history of pubic and axillary hair development over several months. Her breast pubertal status was Tanner stage 3 or 4, and her bone age was advanced at the first visit. Her levels of luteinizing hormone and follicle-stimulating hormone were elevated at 0.7 and 3.3 mIU/mL, respectively. Menarche occurred at 9.6 years of age, and the diagnosis of CPP was made. Her head MRI showed no brain tumor. She did not receive luteinizing hormone-releasing hormone analogue treatment at the time. Her adult height was 126.0 cm (-6.1 SD) at 17 years of age. We identified a novel, de novo splicing mutation (c.4012+1G>C) in the KMT2A gene by trio whole-exome sequencing, thus confirming the diagnosis of WSS.

Conclusions: CPP should be considered as a rare complication of WSS.