ESPE Abstracts

Introduction: Klinefelter syndrome (KS) is most common sex chromosomal aneuploidy in males. The typical clinical features are tall stature with long extremities, small testis, and learning disabilities. Three M syndrome is an extremely rare genetic disorder characterized by short stature, craniofacial abnormality and skeletal malformations. We report a unique case of short stature in KS due to three M syndrome.

Case: A 9-year-old boy previously diagnosed with KS, visited the department of pediatric endocinology due to his short stature. He was born at gestational age of 40 weeks through normal delivery and with a birth weight of 2840 g (5th percentile). There were no specific findings other than cryptorchidism at birth. Orchiopexy was performed at the age of 4, and at that time he was accompanied by developmental delay. Chromosomal analysis revealed a 47,XXY karyotype. When he presented to our clinic, his height were 119.2 cm (-2.70 standard deviation score [SDS]) and weight was 18.8kg (- 3.72 SDS). The mid parental height is 170cm (father’s height, 171cm; mother’s height, 156cm). There was no family history of short stature. The head circumference was 49cm (near 50 percentile), and it was relatively large compared to the height and weight. Both testicles were palpable with 2cc. His bone age was 9 years. There was no skeletal malformation other than mild scoliosis. Serum levels of insulin-like growth factor 1 (IGF-1) was 106.0 ng/mL (normal range: 136-308 ng/mL). The other pituitary hormone levels including thyroid hormone were normal. In the GH provocation test, the peak GH levels after arginine and L-dopa were 6.69 and 7.87 ng/mL respectively. Next generation sequencing for short stature revealed a compound heterozygous CUL7 mutation, c.1823A>G (p. Glu608Gly) and c.364C〉G (p.Leu122Val). Recombinant human GH therapy was initiated (0.64 U/kg/wk). After 1 year of GH therapy, his height was 127.3 cm (-1.97 SDS), and his height velocity increased from 3.4 to 8.1 cm/yr. No adverse events were observed during GH treatment. We will monitor the progress of growth and puberty of patient and consider the sex hormone replacement.

Conclusion: This study reports a boy with short stature, in which a unique combined case of KS and compound heterozygous CUL7 mutation was identified. We report that growth hormone therapy is effective in this patient.