Two cases with severe lethal course of Costello syndrome associated with HRAS p.G12C and p.G12D.
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Two cases with severe lethal course of Costello syndrome associated with HRAS p.G12C and p.G12D. / Lorenz, Sybille; Petersen, Christine; Kordaß, Ulrike; Seidel, Heide; Zenker, Martin; Kutsche, Kerstin.
In: EUR J MED GENET, Vol. 55, No. 11, 11, 2012, p. 615-619.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Two cases with severe lethal course of Costello syndrome associated with HRAS p.G12C and p.G12D.
AU - Lorenz, Sybille
AU - Petersen, Christine
AU - Kordaß, Ulrike
AU - Seidel, Heide
AU - Zenker, Martin
AU - Kutsche, Kerstin
PY - 2012
Y1 - 2012
N2 - Costello syndrome (CS) is a rare congenital disorder characterized by severe failure to thrive, coarse facial appearance, cardiac and skin abnormalities, developmental delay, intellectual disability, and predisposition to malignancies. Heterozygous de novo germline mutations in the proto-oncogene HRAS cause CS. About 80% of patients share the same mutation resulting in the amino acid change p.G12S and present a relatively homogeneous phenotype. 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. We report two new patients with the HRAS p.G12C and p.G12D substitutions and a severe neonatal manifestation causing death at the age of three months and 13 days, respectively. Both patients had particularly severe heart involvement with hypertrophic cardiomyopathy and tachyarrhythmia, generalized edema, and respiratory distress. In one case, hypertrophic cardiomyopathy was already noted prenatally. These cases together with other individuals harboring the rare HRAS mutations p.G12C, p.G12V, p.G12D, and p.G12E provide further evidence for a genotype-phenotype correlation that could be of importance for counseling and medical management.
AB - Costello syndrome (CS) is a rare congenital disorder characterized by severe failure to thrive, coarse facial appearance, cardiac and skin abnormalities, developmental delay, intellectual disability, and predisposition to malignancies. Heterozygous de novo germline mutations in the proto-oncogene HRAS cause CS. About 80% of patients share the same mutation resulting in the amino acid change p.G12S and present a relatively homogeneous phenotype. 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. We report two new patients with the HRAS p.G12C and p.G12D substitutions and a severe neonatal manifestation causing death at the age of three months and 13 days, respectively. Both patients had particularly severe heart involvement with hypertrophic cardiomyopathy and tachyarrhythmia, generalized edema, and respiratory distress. In one case, hypertrophic cardiomyopathy was already noted prenatally. These cases together with other individuals harboring the rare HRAS mutations p.G12C, p.G12V, p.G12D, and p.G12E provide further evidence for a genotype-phenotype correlation that could be of importance for counseling and medical management.
KW - Humans
KW - Male
KW - Female
KW - Infant
KW - Fatal Outcome
KW - Infant, Newborn
KW - Genetic Association Studies
KW - Mutation, Missense
KW - Costello Syndrome/diagnosis/genetics
KW - Proto-Oncogene Proteins p21(ras)/genetics
KW - Humans
KW - Male
KW - Female
KW - Infant
KW - Fatal Outcome
KW - Infant, Newborn
KW - Genetic Association Studies
KW - Mutation, Missense
KW - Costello Syndrome/diagnosis/genetics
KW - Proto-Oncogene Proteins p21(ras)/genetics
M3 - SCORING: Journal article
VL - 55
SP - 615
EP - 619
JO - EUR J MED GENET
JF - EUR J MED GENET
SN - 1769-7212
IS - 11
M1 - 11
ER -
