Endocrine Abstracts

Introduction: CHARGE syndrome is a rare autossomal dominant genetic disorder with an estimated birth incidence of 1:10000. It affects multiple organ systems and can have a variable phenotypic expression.

Case report: 34-years-old man, referred to Endocrinology in the context of bilateral gynecomastia. He had an acute corneal hydrops which was treated by ophthalmology. Physical examination showed short stature (149 cm), obesity (BMI 31.5 kg/m²), micropenis and cryptorchidism. He presented other problems: coloboma of the iris, bilateral hearing loss, anosmia, craniofacial dysmorphisms (abnormal ear shape, microstomia) and intellectual disability. Patient’s investigation included among others: breast ultrasound which revealed bilateral gynecomastia; testicular ultrasound that demonstrated an empty scrotal sac with the atrophic testes in the inguinal canals; biochemical evaluation showed hypogonadotrophic hypogonadism (FSH 0.42 mUI/ml (n:1.5–12.4), LH<0.10 mUI/ml (n:1.7–8.6), total testosterone 0.08 ng/ml (n:2.8–8.0) and a low IGF-1 12 ng/ml (n:140–405). Pituitary had a 3 mm height on MRI; Karyotype result was normal male (46, XY); He started monthly 250 mg/ml enanthate testosterone with poor compliance. Otolaryngology evaluation excluded choanal stenosis/atresia (peri-nasal sinuses CT showed only exuberant deviation to the left of the nasal septum) and confirmed moderate sensorineural hearing loss (audiogram with about 50 dB hearing threshold bilaterally and normal tympanogram) but the patient refused auditory prosthesis. His echocardiogram was normal. Family history was irrelevant for congenital malformations, intellectual disability, deafness or vision loss and endocrinological problems. CHARGE Syndrome was suspected and molecular study of CHD7 gene was requested. A heterozygous pathogenic variant was identified [c.3106C>T, (p.Arg1036Ter)] and clinical suspicion was confirmed.

Conclusion: CHARGE acronym stands for C–coloboma, H–heart disease, A–atresia choanae, R–retarded growth and retarded development and/or CNS anomalies, G–genital hypoplasia, and E–ear anomalies and/or deafness. Diagnostic criteria currently combined major and minor features are used. Pathogenic variants in CDH7 gene are found in around 80% of CHARGE patients. We present CHARGE Syndrome referred to our clinic due to gynecomastia. Most of CHARGE syndrome patients are diagnosed in childhood infancy and rarely in adulthood. With this clinical report we would like to alert that in the presence of hypogonadotrophic hypogonadism associated with suggestive features, this diagnosis should be considered.