A Case Series of Hypogonadism in 22q11.2 Deletion Syndrome: Is It Time to Check the Gonadal Axis?

22q11.2 deletion syndrome is a multifaceted disorder most characterized by congenital cardiac anomalies, immunodeficiency, and psychiatric conditions. Endocrine abnormalities such as hypoparathyroidism and growth hormone deficiency are well documented, but hypogonadism remains rarely reported in this patient population. Only 1 case of hypogonadism has been reported in a patient with multiple other comorbidities which may have contributed to the condition. The relationship between 22q11.2 deletion syndrome and hypogonadism is not well understood. We report 2 male patients with 22q11.2 deletion syndrome and low testosterone levels. The first patient was a 25-year-old male with Tetralogy of Fallot and hypoparathyroidism who presented with balanitis and was found to have low testosterone. Evaluation for causes, including pituitary imaging and hormone panels, was unremarkable. The second patient was a 20-year-old male with a history of growth hormone deficiency and hypogonadism, scoliosis, and neurodevelopmental disorders who had low testosterone levels. No identifiable causes were found. Mechanisms include disruptions in the hypothalamic-pituitary-gonadal axis during embryonic development or testicular dysfunction. Impaired function of synaptosomal-associated protein 29, a gene located within the 22q11.2 region, may contribute to testosterone deficiency. The rarity of reported hypogonadism in 22q11.2 deletion syndrome suggests that it may be underdiagnosed due to a lack of routine screening protocols. Further studies evaluating testosterone, LH, and FSH levels in this population are warranted to establish prevalence and determine whether routine endocrine assessment should be incorporated into clinical guidelines.