Pinto G et al. (2005) CHARGE syndrome includes hypogonadotrophic hypogonadism and abnormal olfactory bulb development. J Clin Endocrinol Metab 90: 5621–5626

Children with CHARGE SYNDROME have a collection of congenital abnormalities including growth retardation and genital hypoplasia, but the endocrine status of these patients is rarely reported.

Pinto and colleagues studied gonadotropic-axis function and growth parameters in 32 children (20 male and 12 female). In addition, they performed MRI scans of the hypothalamopituitary and olfactory-bulb regions, and analyzed patients' sense of smell. Of 20 boys, 19 had micropenis, cryptorchidism, or both, consistent with fetal hypogonadotropic hypogonadism. The majority had extremely low testosterone levels during the neonatal peak period, and showed variable responses to infusion with human chorionic gonadotropin and stimulation with gonadotropin-releasing hormone during the first year of life, which did not correlate with clinical abnormalities or testosterone levels. The majority of females did not respond to stimulation with gonadotropin-releasing hormone. Despite correction of cardiovascular and nutritional problems, the mean height of children at 5 years of age was below average (−2.0 ± 0.2 SDs); however, growth-hormone deficiency was diagnosed in only three patients. Olfactory-bulb development was found to be abnormal in all individuals examined (n = 18). These patients also showed abnormal olfactory function, and therefore fitted the criteria for Kallmann syndrome, which combines hypogonadotropic hypogonadism with deficiencies in sense of smell due to olfactory-bulb aplasia or hypoplasia.

If these findings are confirmed in follow-up studies, olfactory-bulb abnormalities might become a major criterion for CHARGE syndrome, which could help in the early diagnosis of prepubertal hypogonadotropic hypogonadism.