De la Chapelle syndrome: clinical and laboratory characteristics of 4 patients

We describe 4 cases of 46,XX testicular disorder of sex development. Depending on the presence of the SRY gene, two variants of this disease are distinguished: SRY-positive and SRY-negative ones. The SRY (sex-determining region Y) gene is involved in differentiation of Sertoli cells and development of the testes. The pathogenesis of the disease in SRY-positive patients is related to translocation of the SRY gene from the Y chromosome to the X chromosome. The pathogenesis of the disease in SRY-negative patients is associated with overexpression of genes (SOX9, SOX3, etc.) responsible for the development of male genitalia or inadequate gene expression (WNT4, RSPO1, etc.) responsible for the development of female genitalia. The patients had a hermaphroditic genital structure with a masculinization score (EMS) of 6 and 11 and were SRY-negative in 50% of cases; 50% of the patients were SRY-positive with full masculinization, microorchidism, and gynecomastia. All children underwent a hormonal examination in the neutral and pubertal periods. Patients who reached pubertal age developed partial and total hypergonadotropic hypogonadism. The patients have had no need in substitution therapy with testosterone. One of the patients underwent a semiological analysis that revealed necrozoospermia and oligoasthenoteratozoospermia. A SRY-negative patient with cryptorchidism underwent biopsy of the cryptorchid gonad; no Leydig cells were found.