Positive genetic test led to an early diagnosis of myxoma in a 4-year-old boy
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《血管的通路杂志》
Departments of Pediatric Cardiac Surgery and Pediatric Cardiology, Hospital for Children and Adolescents, University of Helsinki, P.O.B. 281, 00029 HUS, Helsinki, Finland
Abstract
Less than 10% of cardiac myxomas are familial. These familial cases are related to Carney complex, a multiple neoplasia and lentiginosis syndrome. Mutations in the PRKAR1alpha gene are the cause of Carney complex in most patients. We report a boy, who had PRKAR1alpha gene mutation, and atrial myxoma that was diagnosed in a routine echocardiographic study at the age of four years. Surgical excision of myxoma was performed. This case demonstrates the benefit of screening genetically the kindreds of patients with familial myxomas, and the importance of close follow-up of individuals affected with this mutation irrespective of age.
Key Words: Cardiac myxoma; PRKAR1alpha gene; Cardiac surgery; Genetic testing
1. Introduction
Myxoma is the most common primary cardiac tumor. It is usually sporadic. Less than 10% of myxomas are familial and transmitted in an autosomal dominant way [1–4]. Although familial myxomas may be transmitted without any associated disorders, they may present as a component of a Carney complex, a familial multiple neoplasia, including myxomas at various sites, endocrine tumors, and spotty pigmentation of the skin [3,4]. Molecular genetic studies show that mutations in the PRKAR1alpha gene, encoding the R1alpha regulatory subunit of cyclic-Amp-dependent protein kinase A, are the cause of Carney complex in most patients [5]. We present an asymptomatic patient with a family history of myxomas and a positive gene test for mutation of PRKAR1alpha gene, who developed a left atrial myxoma during follow-up.
2. Case report
The patient is a 4-year-old boy, whose father had been operated on for multiple cardiac myxomas at the age of 16 years. In addition, four out of six of the father's uncles had a history of cardiac myxomas. In genetic testing, our patient and his father were found to be positive for the PRKAR1alpha gene mutation. The patient was asymptomatic with no other manifestations of Carney complex. Since birth he had been followed-up regularly by echocardiography. He was found to have normal cardiac anatomy and normal myocardial function. At the age of four years, at a routine follow-up visit, a 12 mm x 9 mm tumor was detected in the left atrium by echocardiography (Fig. 1). The tumor did not interfere with pulmonary venous return or the function of the mitral valve. He underwent surgical excision of the pediculated tumor. The tumor was attached to the interatrial septum. In histopathologic examination, the tumor had typical features of myxoma. The patient's recovery was uneventful. At the last follow-up, six months after the operation, there were no signs of recurrent or residual tumor. He is scheduled for regular follow-up every six to twelve months.
3. Discussion
Comparison of clinical and pathologic features among patients with non-familial and familial myxomas has shown differences in prevalence, tumor location and clinical course [2]. Sporadic cardiac myxomas typically occur in middle-aged women. They are usually single and located in the left atrium and attached to the interatrial septum. Familial cardiac myxomas are related to Carney complex. Myxoma may be the only manifestation of this syndrome. It is most commonly found in young men [2]. Patients with Carney complex may have multiple cardiac myxomas at any intracardiac location [1,2]. Review of the literature and report of four cases are presented by Edwards and coworkers [6]. Although these tumors are benign, they can lead to flow obstruction or embolization and, therefore, pose substantial risks of morbidity and mortality. Cerebrovascular accident or myocardial infarction may be the first manifestation of the disease. Therefore, recognition and close follow-up of individuals affected by the Carney complex for early diagnosis of myxomas is of vital importance. Elective surgical removal is indicated whenever diagnosis of cardiac myxoma is made [7].
The association of the PRKAR1alpha gene mutation with familial cardiac myxoma was just reported in Intern Med 2005 by Kojima et al. [8]. Mabuchi et al. analyzed PRKAR1alpha gene in seven patients with cardiac myxoma. Two of them had familial myxomas and had mutations of the gene, whereas no mutations were identified in five patients with non-familial cardiac myxomas [8]. In the present patient, the positive PRKAR1alpha gene diagnosis preceded that of cardiac myxoma. Therefore, this asymptomatic child was followed up since birth. A left atrial myxoma was diagnosed at the age of four years. He had no other manifestations of Carney complex. Interestingly, he was exceptionally young to develop cardiac myxoma.
Our case highlights the benefit of genetic screening for familial cardiac myxoma. Because of a high risk of developing cardiac myxoma a close echocardiographic follow-up is recommended for patients diagnosed with the PRKAR1alpha gene mutation regardless of age.
References
Wilkes D, McDermott D, Basson CT. Clinical phenotypes and molecular genetic mechanisms of Carney complex. 2005; 6:501–508.
Carney JA. Differences between nonfamilial and familial cardiac myxoma. Am J Surg Pathol 1985; 9:53–55.
Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, Pras E, Chrousus GP. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996; 97:699–705.
Milunsky J, Huang XL, Baldwin CT, Farah MG, Milunsky A. Evidence for genetic heterogeneity of the Carney complex. Cancer Genet Cytogenet 1998; 106:173–176.
Casey M, Vaughan JH, Hatcher CJ, Winter JM, Weremowicz S, Montgomery K, Morton CC, Basson CT. Mutations in the protein kinase A R1 regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 2000; 106:R31–R38.
Edwards A, Bermudez C, Piwnka G, Berr ML, Zamorano J, Larrain E, Franck R, Gonzales M, Alvarez E, Maiers E. Carney's syndrome: complex myxomas. Report of four cases and review of the literature. Cardiovasc Surg 2000; 10:264–275.
Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp RB. Cardiac Tumor in Cardiac Surgery 2003;Philadelphia: Churchill Livingstone.
Kojima S, Sumiyoshi M, Watanabe Y, Suwa S, Matsumoto M, Nakata Y, Daida H. A Japanese case of familial cardiac myxoma associated with a mutation of the PRKAR1alpha gene. Intern Med 2005; 44:607–610.(Juha Puntila, Tapio Hakal)
Abstract
Less than 10% of cardiac myxomas are familial. These familial cases are related to Carney complex, a multiple neoplasia and lentiginosis syndrome. Mutations in the PRKAR1alpha gene are the cause of Carney complex in most patients. We report a boy, who had PRKAR1alpha gene mutation, and atrial myxoma that was diagnosed in a routine echocardiographic study at the age of four years. Surgical excision of myxoma was performed. This case demonstrates the benefit of screening genetically the kindreds of patients with familial myxomas, and the importance of close follow-up of individuals affected with this mutation irrespective of age.
Key Words: Cardiac myxoma; PRKAR1alpha gene; Cardiac surgery; Genetic testing
1. Introduction
Myxoma is the most common primary cardiac tumor. It is usually sporadic. Less than 10% of myxomas are familial and transmitted in an autosomal dominant way [1–4]. Although familial myxomas may be transmitted without any associated disorders, they may present as a component of a Carney complex, a familial multiple neoplasia, including myxomas at various sites, endocrine tumors, and spotty pigmentation of the skin [3,4]. Molecular genetic studies show that mutations in the PRKAR1alpha gene, encoding the R1alpha regulatory subunit of cyclic-Amp-dependent protein kinase A, are the cause of Carney complex in most patients [5]. We present an asymptomatic patient with a family history of myxomas and a positive gene test for mutation of PRKAR1alpha gene, who developed a left atrial myxoma during follow-up.
2. Case report
The patient is a 4-year-old boy, whose father had been operated on for multiple cardiac myxomas at the age of 16 years. In addition, four out of six of the father's uncles had a history of cardiac myxomas. In genetic testing, our patient and his father were found to be positive for the PRKAR1alpha gene mutation. The patient was asymptomatic with no other manifestations of Carney complex. Since birth he had been followed-up regularly by echocardiography. He was found to have normal cardiac anatomy and normal myocardial function. At the age of four years, at a routine follow-up visit, a 12 mm x 9 mm tumor was detected in the left atrium by echocardiography (Fig. 1). The tumor did not interfere with pulmonary venous return or the function of the mitral valve. He underwent surgical excision of the pediculated tumor. The tumor was attached to the interatrial septum. In histopathologic examination, the tumor had typical features of myxoma. The patient's recovery was uneventful. At the last follow-up, six months after the operation, there were no signs of recurrent or residual tumor. He is scheduled for regular follow-up every six to twelve months.
3. Discussion
Comparison of clinical and pathologic features among patients with non-familial and familial myxomas has shown differences in prevalence, tumor location and clinical course [2]. Sporadic cardiac myxomas typically occur in middle-aged women. They are usually single and located in the left atrium and attached to the interatrial septum. Familial cardiac myxomas are related to Carney complex. Myxoma may be the only manifestation of this syndrome. It is most commonly found in young men [2]. Patients with Carney complex may have multiple cardiac myxomas at any intracardiac location [1,2]. Review of the literature and report of four cases are presented by Edwards and coworkers [6]. Although these tumors are benign, they can lead to flow obstruction or embolization and, therefore, pose substantial risks of morbidity and mortality. Cerebrovascular accident or myocardial infarction may be the first manifestation of the disease. Therefore, recognition and close follow-up of individuals affected by the Carney complex for early diagnosis of myxomas is of vital importance. Elective surgical removal is indicated whenever diagnosis of cardiac myxoma is made [7].
The association of the PRKAR1alpha gene mutation with familial cardiac myxoma was just reported in Intern Med 2005 by Kojima et al. [8]. Mabuchi et al. analyzed PRKAR1alpha gene in seven patients with cardiac myxoma. Two of them had familial myxomas and had mutations of the gene, whereas no mutations were identified in five patients with non-familial cardiac myxomas [8]. In the present patient, the positive PRKAR1alpha gene diagnosis preceded that of cardiac myxoma. Therefore, this asymptomatic child was followed up since birth. A left atrial myxoma was diagnosed at the age of four years. He had no other manifestations of Carney complex. Interestingly, he was exceptionally young to develop cardiac myxoma.
Our case highlights the benefit of genetic screening for familial cardiac myxoma. Because of a high risk of developing cardiac myxoma a close echocardiographic follow-up is recommended for patients diagnosed with the PRKAR1alpha gene mutation regardless of age.
References
Wilkes D, McDermott D, Basson CT. Clinical phenotypes and molecular genetic mechanisms of Carney complex. 2005; 6:501–508.
Carney JA. Differences between nonfamilial and familial cardiac myxoma. Am J Surg Pathol 1985; 9:53–55.
Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, Pras E, Chrousus GP. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996; 97:699–705.
Milunsky J, Huang XL, Baldwin CT, Farah MG, Milunsky A. Evidence for genetic heterogeneity of the Carney complex. Cancer Genet Cytogenet 1998; 106:173–176.
Casey M, Vaughan JH, Hatcher CJ, Winter JM, Weremowicz S, Montgomery K, Morton CC, Basson CT. Mutations in the protein kinase A R1 regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 2000; 106:R31–R38.
Edwards A, Bermudez C, Piwnka G, Berr ML, Zamorano J, Larrain E, Franck R, Gonzales M, Alvarez E, Maiers E. Carney's syndrome: complex myxomas. Report of four cases and review of the literature. Cardiovasc Surg 2000; 10:264–275.
Kouchoukos NT, Blackstone EH, Doty DB, Hanley FL, Karp RB. Cardiac Tumor in Cardiac Surgery 2003;Philadelphia: Churchill Livingstone.
Kojima S, Sumiyoshi M, Watanabe Y, Suwa S, Matsumoto M, Nakata Y, Daida H. A Japanese case of familial cardiac myxoma associated with a mutation of the PRKAR1alpha gene. Intern Med 2005; 44:607–610.(Juha Puntila, Tapio Hakal)