A Unique Case of PPP1R12A ‐Related Urogenital and Brain Malformation Syndrome Phenotypically Overlapping With VACTERL Association, With Additional Literature Review of Previously Described Phenotypes
Year: 2026
Type: article
Abstract: PPP1R12A-related urogenital and brain malformation syndrome (UBMS) is a rare genetic disorder caused by pathogenic variants in PPP1R12A, which encodes a regulatory subunit of myosin phosphatase. We report a 46,XY male with a heterozygous de novo pathogenic variant in PPP1R12A, c.2629del (p.S877Pfs*38). He presented with features consistent with UBMS, including bilateral cryptorchidism, Müllerian duct remnants, tracheoesophageal fistula, anal atresia, and global developmental delay. Notably, he exhibited cardiac anomalies and hepatic cirrhosis not previously reported in individuals with PPP1R12A-related UBMS, including bilateral pulmonary artery hypoplasia and mitral valve prolapse; however, a causal relationship between these findings and the PPP1R12A variant has not been established. His presentation also has significant overlap with VACTERL association. This case reinforces the association between PPP1R12A dysfunction and complex urogenital and gastrointestinal malformations while expanding the phenotypic spectrum to include novel cardiac and hepatic findings. Collectively, these findings raise the possibility of an expanded phenotypic spectrum associated with PPP1R12A-related disease, though additional data is needed to determine whether all associated features are attributable to the variant.
DOI: 10.1002/ajmg.a.70340
Institutions: University of Kentucky, University of Kentucky HealthCare
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7225659632