Endocrine Abstracts

JOINT3585

Introduction: KBG syndrome is a rare autosomal dominant disorder characterized by specific craniofacial features (triangular face, macrodontia, a single upper central incisor), short stature, and skeletal abnormalities. The condition is caused by heterozygous mutations or deletions in the ANKRD11 gene. Herewe present a case of a patient diagnosed with KBG syndrome, monitored in our clinic due to short stature.

Case Report: A 9-year-9-month-old male patient presented to our clinic with short stature. His history revealed a birth weight of 2450 grams at 35 weeks of gestation. Short stature was noticed from six months of age. He had been followed by pediatric gastroenterology due to recurrent vomiting, which resolved after a diagnosis of cholelithiasis and subsequent cholecystectomy. Parental consanguinity was noted. The mother’s height was 150.9 cm, and the father’s height was 168 cm (mid-parental height: 165.9 cm). The patient’s physical examination showed a weight of 21 kg (-2.59 SD), height of 120 cm (-2.79 SD), and BMI of 14.5 (-1.29 SD). He exhibited atypical facial features (triangular face, long philtrum), macrodontia and Tanner stage 1 puberty. Laboratory findings included IGF-1 at 140 ng/ml (0/+1 SD), IGFBP-3 at 3817 ng/ml (+1/+2 SD), normal thyroid function tests, negative celiac antibodies and a bone age of 6 years and 6 months. The patient was monitored for growth velocity. At 10 years and 8 months of age, he entered puberty, with a pubertal growth velocity of 5.2 cm/year. A growth hormone stimulation test revealed a peak response of 11.2 ng/ml. Genetic testing confirmed KBG syndrome by identifying a heterozygous c.5273_5274dup variant in the ANKRD11 gene, consistent with the patient’s atypical facial features, macrodontia, and short stature. Due to inadequate pubertal growth and short stature, somatropin therapy was initiated. Growth velocity improved to 7.7 cm/year with treatment. At his last follow-up (15 years and 9 months), his chronological age was 15 years and 9 months, height age was 12 years and 8 months, bone age was 15 years, weight was 47.1 kg (-2.14 SD), height was 156.9 cm (-2.36 SD), and his pubertal examination corresponded to Tanner stage 4.

Discussion/Conclusion: Short stature is a common feature of KBG syndrome, and achieving target height is rare in affected individuals. Growth hormone therapy may be effective in patients with KBG syndrome presenting with significant prepubertal short stature, even in the absence of growth hormone deficiency. However, larger-scale studies are needed to evaluate treatment efficacy and safety comprehensively.