Lucía Miranda-Alcaraz, Simone Carbonera, Mónica Mora-Gómez, Natalia Gallego-Zazo, Inmaculada Guillén, Elena Padilla, Gaia Visani, Alessia Asaro, Valeria Vásquez-Amell, Mario Cazalla, Manuel Rodríguez-Canó, Cristina Silván, Pedro Arias, Juan Andrés Jiménez-Estrada, Tomás Valle, Alejandro Cruz-Utrilla, Pilar Escribano-Subías, Nuria Ochoa Parra, María Jesús Del Cerro Marín, Julián Nevado, Spanish PAH Consortium, Pablo Lapunzina, Fabio Sirchia, Jair Tenorio-Castano
Pathogenic variants in PORCN cause focal dermal hypoplasia (FDH/Goltz syndrome), an X-linked dominant disorder historically considered lethal in males, with milder presentations now recognized as PORCN non-Goltz spectrum (PONGOS). We report three male patients identified by exome sequencing: one with a mosaic de novo variant (c.727C>T; p.Arg243*) showing FDH features, and two siblings with an inherited non-mosaic variant (c.1315T>G; p.Trp439Gly) from their unaffected carrier mother with a PONGOS phenotype. These cases confirm that male survival is possible with both mosaic and non-mosaic PORCN variants and expand the clinical and molecular spectrum of the disease. Our findings highlight the role of residual protein function in clinical variability and have important implications for diagnosis, genetic counseling, and management in families with apparently unaffected carrier mothers.