title: Recurrent left atrial myxomas in Carney complex: a genetic cause of multiple strokes that can be prevented.
abstract: BACKGROUND
  Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical, and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described. The regulatory subunit (R1A) of the protein kinase gene (PRKAR1A) is mutated in >60% of patients with Carney complex.
  
  
  METHODS
  We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere; a total of 7 patients with 16 recurrent atrial myxomas and >14 episodes of strokes were identified.
  
  
  RESULTS
  Neurologic deficits were reported; in 1 patient, an aneurysm developed at the site of a previous stroke. All patients were females, were also diagnosed with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, and c.177+1G>A) were located in exons 3 to 5 and introns 2 to 3, and all led to a non-sense PRKAR1A mRNA.
  
  
  CONCLUSIONS
  Female patients with Carney complex appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes.
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: George
authors.initials: G
authors.lastname: Briassoulis
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuburovic
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Xekouki
authors.forename: Nicholas
authors.initials: N
authors.lastname: Patronas
authors.forename: Meg F
authors.initials: MF
authors.lastname: Keil
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lyssikatos
authors.forename: Mila
authors.initials: M
authors.lastname: Stajevic
authors.forename: Gordana
authors.initials: G
authors.lastname: Kovacevic
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000303:Adrenal Cortex Diseases / Q000235:genetics; D000328:Adult; D056733:Carney Complex / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D018389:Codon, Nonsense; D003480:Cushing Syndrome / Q000235:genetics; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D038524:Diffusion Magnetic Resonance Imaging; D004452:Echocardiography; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control
chemical_list: D018389:Codon, Nonsense; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human