Case Report: KBG syndrome in an adult presenting with diabetes, gout, and hypogonadism

KBG syndrome (MIM #148050) is an autosomal dominant disorder caused by pathogenic variants in ANKRD11 or 16q24.3 microdeletions, classically recognized in children through macrodontia, short stature, skeletal anomalies, and neurodevelopmental delay. How the syndrome presents to adult internal medicine remains poorly documented. A 31-year-old man was admitted with new-onset diabetes (blood glucose 20.0 mmol/L) and an acute gout flare, superimposed on congenital sensorineural deafness, repaired cryptorchidism, and 10 years of recurrent gout. Examination revealed macrodontia of the upper central incisors, kyphoscoliosis, brachydactyly with fifth-finger clinodactyly, bilateral gynecomastia, and small soft testes. Investigations showed preserved β-cell reserve with delayed insulin and C-peptide peaks, negative islet autoantibodies, repeatedly borderline-low testosterone with inadequately normal gonadotropins, and 24-h urinary uric acid excretion at the lower end of the reference range. Maternally inherited diabetes and deafness was initially suspected because diabetes coexisted with deafness, but the burden of congenital anomalies prompted trio whole-exome sequencing, which identified a de novo heterozygous ANKRD11 frameshift (NM_013275.6: c.1903_1907del, p.Lys635Glnfs*26). He was treated with liraglutide, febuxostat, colchicine, and atorvastatin. Over 33 months of follow-up, glycated hemoglobin remained between 4.5% and 5.3% and thyroid function normalized, yet serum urate stayed markedly elevated at nearly every routine measurement, and one gout flare required readmission. This case illustrates delayed recognition of KBG syndrome during adulthood: the characteristic dental, skeletal, and developmental signs had been present since early childhood, yet the syndrome was named only when an acquired metabolic cluster—diabetes, gout, and hypogonadism—brought him to adult endocrine care. The decade of gout preceding glucose intolerance is, to our knowledge, the first such report in KBG syndrome and remains a single observation; whether it reflects an intrinsic urate-handling defect is a hypothesis that merits further study rather than an established association. Careful attention to dental, skeletal, and developmental clues in atypical diabetes can end a long diagnostic odyssey.