Endocrine Abstracts

JOINT1263

Background: CHARGE syndrome is a rare genetic disorder characterized by a spectrum of anomalies, including coloboma, heart defects, choanal atresia, growth retardation, genital hypoplasia, and ear/hearing abnormalities. It is caused by mutations in the CHD7 gene and follows an autosomal dominant inheritance pattern. One of the primary features of CHARGE syndrome is hypogonadotropic hypogonadism (HH), leading to delayed or absent puberty in both males and females. Short stature is also common, affecting 60-72% of individuals, though the underlying mechanisms remain poorly understood.

Method: We reviewed the clinical data and investigations of a Romanian patient diagnosed with CHARGE syndrome who was admitted to our hospital in February 2024.

Case description: The patient exhibited multiple features of CHARGE syndrome, including cochlear implants, surgically corrected choanal atresia, left testicular atresia, and right testicular orchidopexy. Whole-exome sequencing (WES) identified a heterozygous pathogenic variant, NM_017780.4:c.4695C>T, in the CHD7 gene, confirming the clinical suspicion and genetic diagnosis of CHARGE syndrome in 2020. At the time of consultation, the 14-year-old patient had a significantly below-average growth trajectory, with a height of -3.01 standard deviations (SD) and a developmentally small penis (-2.5 SD). Hormonal tests revealed low levels of FSH (0.53 mUI/ml), LH (<0.03 mUI/ml), and testosterone (0.14 ng/ml), indicating hypogonadotropic hypogonadism. His Tanner stage was also inconsistent with his chronological age, further confirming the diagnosis of HH. Two years prior, the patient’s growth hormone levels were normal. However, recent stimulation tests indicated growth hormone deficiency. IGF-1 values were at the lower limit (-2.09 SD). As a result, hormone replacement therapy (HRT) with somatropin and Androgel was initiated. After seven months of somatropin treatment, his height improved from -3.01 SD to -2.68 SD. However, Androgel proved ineffective, prompting a switch to testosterone enanthate in January 2025. Following this change, the patient’s penile length increased to 6 cm. Additionally, autoimmune thyroiditis was detected via ultrasound during his first consultation, although his thyroid function remained normal.

Conclusions: Individuals with CHARGE syndrome commonly experience delayed or absent puberty due to hypogonadotropic hypogonadism. Hormone replacement therapy, including growth hormone and testosterone, is essential for promoting growth and inducing puberty in these patients. Early intervention can improve outcomes, particularly in terms of physical growth and sexual development.