PPP2R5D-Related Neurodevelopmental Disorder and Multiple Haemangiomas: A Novel Phenotypic Trait?

Abstract

Background: Houge-Janssens syndrome 1 is a condition with onset in early childhood caused by heterozygous pathogenic variants in the PPP2R5D gene, which encodes a B56 regulatory subunit of the serine/threonine protein phosphatase 2A (PP2A). There is evidence that the PP2A-PPP2R5D complex is involved in regulating the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, which is crucial for several cellular processes, including the pathogenesis and progression of haemangiomas.

Case presentation: We report the first PPP2R5D-related neurodevelopmental disorder case from Sardinia, a child with transient hypoglycaemia, facial dysmorphisms, and multiple haemangiomas. Whole Exome Sequencing analysis confirmed the clinical suspicion, detecting the presence of the de novo missense variant c.592G>A in the PPP2R5D gene.

Conclusions: Haemangiomas have never been linked to the syndromic phenotype of the PPP2R5D-associated disorder. The close correlation between the PP2A enzyme and the PI3K/AKT signalling pathway suggests the possible correlation between its dysfunction and activation of haemangiogenesis. Our report highlights a possible link between the PPP2R5D-related disorder and altered angiogenesis, characterizing diffuse haemangiomas as a possible novel phenotypic trait of this condition.