Respiratory system involvement in Costello syndrome.
Costello syndrome (CS) is a multisystem disorder caused by heterozygous germline mutations in the HRAS proto-oncogene. Respiratory system complications have been reported in individuals with CS, but a comprehensive description of the full spectrum and incidence of respiratory symptoms in these patients is not available. Here, we report the clinical course of four CS patients with respiratory complications as a major cause of morbidity. Review of the literature identified 56 CS patients with descriptions of their neonatal course and 17 patients in childhood/adulthood. We found that in the neonatal period, respiratory complications are seen in approximately 78% of patients with transient respiratory distress reported in 45% of neonates. Other more specific respiratory diagnoses were reported in 62% of patients, the majority of which comprised disorders of the upper and lower respiratory tract. Symptoms of upper airway obstruction were reported in CS neonates but were more commonly diagnosed in childhood/adulthood (71%). Analysis of HRAS mutations and their respiratory phenotype revealed that the common p.Gly12Ser mutation is more often associated with transient respiratory distress and other respiratory diagnoses. Respiratory failure and dependence on mechanical ventilation occurs almost exclusively with rare mutations. In cases of prenatally diagnosed CS, the high incidence of respiratory complications in the neonatal period should prompt anticipatory guidance and development of a postnatal management plan. This may be important in cases involving rarer mutations. Furthermore, the high frequency of airway obstruction in CS patients suggests that otorhinolaryngological evaluation and sleep studies should be considered. © 2016 Wiley Periodicals, Inc.
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Natalia
N
Gomez-Ospina
Division of Pulmonary Medicine, Stanford University School of Medicine, Stanford, California.
Christin
C
Kuo
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Amitha Lakshmi
AL
Ananth
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Angela
A
Myers
Epigenomics, Menlo Park, California.
Marie-Luise
ML
Brennan
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
David A
DA
Stevenson
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Jonathan A
JA
Bernstein
Division of Medical Genetics, Stanford University School of Medicine, Stanford, California.
Louanne
L
Hudgins
D056685:Costello Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015619:Respiratory System Abnormalities / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
Costello syndrome; HRAS; obstructive sleep apnea; pulmonary; respiratory; upper airway