46,XY differences of sex development in pontocerebellar hypoplasia type 7 (PCH7): two case reports and systematic review.

We report two cases of 46,XY siblings with pontocerebellar hypoplasia type 7 (PCH7) and conduct a systematic literature review for genetically confirmed PCH7 cases, focusing on phenotypic characteristics, particularly gonadal parameters, and associated genotypic data. Two 46,XY siblings diagnosed with PCH7 were reviewed. Both exhibited hypoplastic male external genitalia, absent uterus, and cryptorchid testes, confirmed through histological assessments showing dysgenesis. A systematic literature search revealed an additional 26 cases of 46,XY PCH7, with neurological involvement noted in all cases except one. The external genitalia were described as abnormal (17/23); however, few of these were hypoplastic male type on pictorial review. Nonlocalized testes (5/5) and absent uterus (4/7) on ultrasonography, elevated FSH (7/7), and low testosterone (3/3) were observed. Besides a novel variant (p.Ile133Thr) in Indian siblings, a total of 25 variants in TOE1 were identified with no specific genotype-phenotype correlation. Testicular development was defective in all PCH7 patients but was variable, with the predominant phenotypic manifestation being testicular regression syndrome/partial gonadal dysgenesis with Müllerian duct regression (TRS/PGD-MDR).