ESPE Abstracts

Background: CHARGE syndrome is a complex of congenital malformations affecting multiple organ systems caused by mutations in CHD7.

Objective and hypotheses: This study was performed to evaluate endocrine dysfunctions including hypogonadotropic hypogonadism, growth hormone deficiency, or hypothyroidism in patients with CHARGE syndrome.

Method: Eighteen patients (10 males and 8 females) with CHARGE syndrome were included. A diagnosis of CHARGE syndrome was made according to the diagnostic criteria by Verloes. All coding exons and exon-intron boundaries of the CHD7 were amplified by PCR and directly sequenced in 14 patients. Clinical features and endocrine functions were evaluated by retrospective chart review.

Results: Nine patients fulfilled the criteria for typical CHARGE syndrome, two patients for partial/incomplete, and seven for atypical CHARGE syndrome. CHD7 mutations were identified in 12 patients: 11 truncating and one complete deletion mutations. Micropenis was found in all 10 boys, 6 of whom had unilateral or bilateral cryptorchidism. Two females and one male were diagnosed with hypogonadotropic hypogonadism during adolescents. LH responses to GnRH stimulation were prepubertal pattern. Mean height- and weight-SDS were −2.54±1.16 and −2.57±1.86, respectively. Of these, short stature of less than 3rd percentile was apparent in 12 patients (66.7%). One female was confirmed to have growth hormone deficiency by L-dopa and insulin tolerance tests at age 8 years. She was previously diagnosed with hypothyroidism at age 6.7 years and treated with levothyroxine, however, brain MRI did not show abnormalities.

Conclusion: Hypogonadotropic hypogonadism has been reported as an endocrine defect in CHARGE syndrome. However, endocrinological evaluation is necessary in patients with CHARGE syndrome. As the ages of the patients in the present study were not in the range that would provide useful information concerning gonadotropin secretion, long-term follow-up is needed to assess endocrine functions in these patients.