Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades.
Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with costello syndrome: case report and review of the literature.
Panel testing for rasopathies identified a novel HRAS mutation (c.179G>A; p.Gly60Asp) in three individuals with attenuated features of Costello syndrome.
Mutations in the RAS-MAPK pathway have recently been reported in both of these syndromes, with HRAS mutations characteristic for CS and BRAF and MEK1/2 mutations for CFC.
We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene.
Other less common lesions in HRAS can induce a milder phenotype on the one hand and a more severe phenotype on the other broadening the spectrum of clinical manifestations in CS-affected individuals.
However, some patients carrying HRAS mutations may exhibit prominent congenital muscular dysfunction, although features of CS may be less obvious, suggesting that germline HRAS mutations may underlie some cases of otherwise unclassified neonatal neuromuscular disorders.
However, some patients carrying HRAS mutations may exhibit prominent congenital muscular dysfunction, although features of CS may be less obvious, suggesting that germline HRAS mutations may underlie some cases of otherwise unclassified neonatal neuromuscular disorders.