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GENATLAS PHENOTYPE

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

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
missense		abnormal protein/gain of function	mutations in exons 12 to 18, substitution of a glycine in position 12 or 13

Remark(s)

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