The etiologic heterogeneity of penile agenesis

Penile agenesis may present as an isolated malformation or in association with other abnormalities, most often of the genitourinary or gastrointestinal tracts. We present 4 cases of penile agenesis that demonstrate die etiologic heterogeneity of this disorder. Patient 1 presented with a hypoplastic left kidney and megacolon without aganglionosis. Patient 2 had no associated malformations but developed atrophy of the kidneys, left greater than right, over the first few years of life. Patients 3 and 4 had associated findings that were incompatible with life. Patient 3 had a short rib polydactyly syndrome, and patient 4 had an unknown malformation syndrome consisting of penile agenesis, renal abnormalities, anal atresia, a cardiac defect and spinal anomalies. The cases herein described and review of the literature demonstrate the variable, usually sporadic presentation of penile agenesis. In patients 1 and 2, the pathogenesis of penile agenesis is likely the result of abnormal development of the genital tubercle and associated mesodermal structures. The multiple malformation syndrome seen in patient 3 suggests a single gene mutation, perhaps analogous to the SOX9 mutations in children with campomelic dysplasia. Patient 4 has a disorder of unknown genesis which shares many features of the VATER association. These cases are important to alert clinicians who care for neonates to the risk of associated findings in newborns with penile agenesis, the range of prognostic and recurrence counseling issues, and the possible pathogenetic mechanisms of this malformation.