Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome

Research output: Contribution to journalArticle

Abstract

Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
JournalCytogenetic and Genome Research
Volume158
Issue number4
DOIs
StatePublished - 1 Sep 2019

Fingerprint

Costello Syndrome
Mutation
Alveolar Rhabdomyosarcoma
Polyhydramnios
Inborn Genetic Diseases
Proto-Oncogenes
Tracheostomy
Hypertrophic Cardiomyopathy
Genetic Association Studies
Left Ventricular Hypertrophy
Growth
Mitogen-Activated Protein Kinases
Intubation
Tachycardia

Keywords

  • Costello syndrome
  • Genotype-phenotype correlation
  • HRAS
  • RAS/MAPK pathway

Cite this

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abstract = "Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.",
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Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome. / Choi, Naye; Ko, Jung Min; Shin, Seung Han; Kim, Ee Kyung; Kim, Han Suk; Song, Mi Kyoung; Choi, Chang Won.

In: Cytogenetic and Genome Research, Vol. 158, No. 4, 01.09.2019, p. 184-191.

Research output: Contribution to journalArticle

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AU - Choi, Naye

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AU - Shin, Seung Han

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AU - Choi, Chang Won

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