Gonadoblastoid Testicular Dysplasia in Walker-Warburg Syndrome

Two male fetuses (18 and 22 weeks gestation) and a 3-month-old male infant (full sibling of the younger fetus) who were diagnosed with Walker-Warburg syndrome (WWS) on the basis of neuropathologic autopsy findings in brain, eyes, and muscle also had micro-orchia and, microscopically, diffuse gonadoblastoid dysplasia in the testes. Both fetuses also had a miniature left ureter and cystic dysplastic left kidney. Testes from control fetuses of 17–24 weeks gestation with normal karyotype and no central nervous system abnormalities (group A, n = 50), a variety of central nervous system abnormalities (group B, n = 50), or an autosomal aneuploidy syndrome with or without central nervous system abnormalities (group C, n = 30) had no diffuse dysplasia, although a single gonadoblastoid seminiferous tubular profile was present in three controls. Testicular morphology was normal in older fetuses and infants with a wide variety of central nervous system malformations (group D, n = 50). We found no evidence of hypogonadotrophic hypogonadism in the three WWS cases to account for the small penis and incompletely descended testes commonly reported in this condition. We concluded that the apparent specificity of the gonadoblastoid testicular dysplasia to WWS suggests that the gene defect directly affects testicular development.