Endocrine Abstracts

Introduction: CHARGE Syndrome (CS) is a rare cause of hypogonadotropic hypogonadism (HH), usually diagnosed in paediatric age when pubertal development is compromised. Herein, we report a case that presented a major criterion and three minor criteria.

Case report: At age ten, the patient was referred to the paediatric endocrinology unit due to phenotypic alterations and psychomotor and cognitive impairment. She had no family history of consanguinity, inherited or genetic disorders. At 8 years of age she was diagnosed with semicircular channels bilateral agenesis with consequent profound bilateral deafness. At physical examination there was a normal stature and weight, facial asymmetry and dysmorphia, low ear implantation, cleft palate and dorsocifoescoliosis. Genital examination revealed normal morphology and a Tanner 2 stage. Pelvic ultrasonography was consistent with small ovaries and uterus, without evidence of follicular activity. Basal FSH and LH were below the normal range without response to LHRH stimulation. CHARGE syndrome was considered and genetic tests were performed. The karyotype was 46 XX and a missense mutation in the CHD7 gene was identified (c.484C>T/p.Q162X). The patient initiated treatment with an estradiol/norgestrel combination at the age of 15 with marked improvement of pubertal development.

Conclusion: CS should be considered in the differential diagnosis of HH particularly in presence of an abnormal phenotype. Mutations in the CHD7 gene cause more than half of all cases of CS and most of the times are new mutations as occurred in the current case. Different malformations may be present but the pattern varies among affected individuals justifying a long term follow up.