TABLE 3.

Genotype–phenotype correlations in Costello syndrome

HRAS mutation	Clinical phenotype
p.G12S	Classic features of CS
p.G12C	Severe neonatal phenotype—severe cardiomyopathy, pleural and pericardial effusion, and lung abnormalities
p.G12D	Severe neonatal phenotype—severe cardiomyopathy, pleural and pericardial effusion, and lung abnormalities
p.G12A	Higher rate of malignancy
p.G12V	Severe cardiomyopathy and tachycardia as well as respiratory distress; typically lethal
p.G13C	Milder symptoms with lower risk for malignant tumors or papillomata, taller stature, and absence of the classic CS ulnar wrist deviation
p.Q22K	Classic features of CS plus congenital myopathy
p.T58I	Facial features tend to be less coarse
p.G60D	Milder phenotype—reported with maternal transmission
p.G60V	Only one case reported—infant death
p.E63K	Classic features of CS plus congenital myopathy
p.E63_D69dup	Milder symptoms—milder intellectual disability, fewer feeding issues, and a lower risk of tumors
p.K117R	Facial features tend to be less coarse
p.A146P	Facial features tend to be less coarse
p.A146T	Milder symptoms—minor skin and joint involvement and milder growth restriction. Microcephaly and sparse, thin hair are also reported.
p.A146V	Facial features tend to be less coarse