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last update : 19-06-2013
Symbol COSTS
Location 11p15.5
Name Costello syndrome
Other name(s) faciocutaneoskeletal syndrome
Corresponding gene HRAS
Other symbol(s) FCS, CSTLO
Main clinical features
  • prenatally increased growth, post natal growth deficiency, mental retardation, coarse facies loose skin of the neck, hand, feet, cardiomyopathy, increased tumor rate (bladder cancer)
  • Genetic determination autosomal dominant
    autosomal recessive
    Related entries including rare forms with neonatal neuromuscular disorders
    Function/system disorder congenital malformation
    mental retardation
    Type disease
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/gain of function mutations in exons 12 to 18, substitution of a glycine in position 12 or 13
  • cases of mosaic for the common HRAS mutation, likely due to a somatic mutation occurring very early in fetal development
  • mostly paternal origin of point mutation among autosomal dominant disease (advanced age at conception in unaffected fathers transmitting the mutation)
  • duplication of Glu37 in the switch I region of HRAS mildly enhanced signal flux through the MAPK and PI3K-AKT cascades resulting from a balancing effect between a profound GAP insensitivity and inefficient binding to effector proteins (demars 2010)
  • Genotype/Phenotype correlations mutation G12A having higher risk of malignancies