Twins With Pathogenic RNF113A Variant Presenting With Testicular Regression Syndrome

RNF113A-related disorders are rare X-linked conditions characterized by neurodevelopmental impairment, endocrine abnormalities, and gonadal dysgenesis. To date, this condition has been documented in only a few individuals. We report 46,XY twin siblings with a hemizygous pathogenic RNF113A variant [c.901C > T, p.(Gln301*)], presenting with a remarkably consistent phenotype that includes microcephaly, corpus callosum dysgenesis, intractable epilepsy, subclinical hypothyroidism, microphallus, and bilateral testicular regression syndrome (TRS). Whole-exome sequencing identified a maternally inherited variant consistent with X-linked recessive inheritance. Despite the absence of testicular tissue, both twins had evidence of prenatal androgen exposure. Thyroid dysfunction evolved during infancy. These cases expand the phenotypic spectrum associated with pathogenic RNF113A variant and provide evidence linking this gene to TRS. They further highlight the importance of whole-exome sequencing in evaluating complex 46,XY disorders of sex development with multisystem involvement. RNF113A should be considered in the genetic evaluation of 46,XY disorder of sex development and TRS, particularly when accompanied with multisystem involvement.