Lateralized overgrowth with vascular malformation caused by a somaticPTPN11pathogenic variant: Another piece added to the puzzle of mosaicRASopathies

• DOI: 10.1002/gcc.23086
• Publication Date: 2022-07-02T10:04:35Z
• Authors: Alessandro Mussa; Antonella Turchiano; Simona Cardaropoli; Paola Coppo; Antonino Pantaleo; Rosanna Bagnulo; Carlotta Ranieri; Matteo Iacoviello; Antonella Garganese; Alessandro Stella; Stefano Gabriele ...; Daniele Bertin; Federica Santoro; Diana Carli; Giovanni Battista...; Nicoletta Resta
• Keywords: PTPN11

Abstract Lateralized/segmental overgrowth disorders (LOs) encompass a heterogeneous group of congenital conditions with excessive body tissue growth. Documented molecular alterations in LOs mostly consist somatic variants genes the PI3KCA/AKT/mTOR pathway or chromosome band 11p15.5 imprinted region anomalies. In some cases, pathogenic RAS/MAPK have been reported. We present first case variant (T507K) PTPN11 causing LO phenotype characterized by severe lateralized overgrowth, vascular proliferation, and cerebral astrocytoma. The T507K was detected DNA from overgrown leg capillary malformation. astrocytoma showed higher allele frequency. A FGFR1 also found tumor tissue, representing second hit on pathway. These findings indicate that cascade overactivation can cause mosaic phenotypes resembling PIK3CA‐related (PROS) cancer predisposition are consistent hypothesis hyperactivation be involved pathogenesis This observation raises issue patients gene expands genotype spectrum treatment options for similar cases through inhibition oversignaling.