RESUMO
Cardiac myxoma is a relatively rare tumour, usually solitary, that occurs primarily in the left atrium of adults, but comprises only 30% of cardiac tumours in children. We recently treated a 12-year-old girl with multiple recurrent myxomas in three cardiac chambers(following surgical resection 3 years earlier). Genomic analysis showed the PKAR1A mutation typical for Carney complex.
Assuntos
Complexo de Carney , Neoplasias Cardíacas , Mixoma , Adulto , Feminino , Criança , Humanos , Complexo de Carney/diagnóstico , Complexo de Carney/genética , Complexo de Carney/patologia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Mixoma/diagnóstico , Mixoma/genética , Mixoma/cirurgia , Átrios do Coração/cirurgiaRESUMO
SUMMARY Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.
Assuntos
Humanos , Feminino , Adulto , Adulto Jovem , Acromegalia/genética , Síndrome de Cushing/genética , Complexo de Carney/genética , Mixoma/cirurgia , Mixoma/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Irã (Geográfico) , MutaçãoRESUMO
Carney complex (CNC) is a rare syndrome of multiple endocrine and non-endocrine tumors. In this paper we present a 23-year-old Iranian woman with CNC who harbored a novel mutation (c.642dupT) in PRKAR1A gene. This patient presented with pituitary macroadenoma, acromegaly, recurrent atrial myxoma, Cushing's syndrome secondary to primary pigmented nodular adrenocortical disease and pigmented schwanoma of the skin. PRKAR1A gene was PCR amplified using genomic DNA and analyzed for sequence variants which revealed the novel mutation resulting in substitution of amino acid cysteine instead of the naturally occurring valine in the peptide chain and a premature stop codon at position 18 (V215CfsX18). This change leads to development of tumors in different organs due to lack of tumor suppressive activity secondary to failure of synthesis of the related protein.
Assuntos
Acromegalia , Complexo de Carney , Síndrome de Cushing , Mixoma , Acromegalia/genética , Adulto , Complexo de Carney/genética , Síndrome de Cushing/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Feminino , Humanos , Irã (Geográfico) , Mutação , Mixoma/genética , Mixoma/cirurgia , Adulto JovemAssuntos
Humanos , Feminino , Adulto , Recidiva , Complexo de Carney/diagnóstico , Complexo de Carney/genética , AVC Isquêmico/diagnóstico , Neoplasias Cardíacas/etiologia , Afasia de Broca/complicações , Complicações Pós-Operatórias/diagnóstico por imagem , Ecocardiografia/métodos , Espectroscopia de Ressonância Magnética/métodos , Ecocardiografia Transesofagiana/métodos , Continuidade da Assistência ao Paciente , Morte Súbita , Embolia/complicações , Neoplasias Cardíacas/cirurgiaRESUMO
Thyroid cancer is the most frequent endocrine malignancy with the majority of cases derived from thyroid follicular cells and caused by sporadic mutations. However, when at least two or more first degree relatives present thyroid cancer, it is classified as familial non-medullary thyroid cancer (FNMTC) that may comprise 3-9% of all thyroid cancer. In this context, 5% of FNMTC are related to hereditary syndromes such as Cowden and Werner Syndromes, displaying specific genetic predisposition factors. On the other hand, the other 95% of cases are classified as non-syndromic FNMTC. Over the last 20 years, several candidate genes emerged in different studies of families worldwide. Nevertheless, the identification of a prevalent polymorphism or germinative mutation has not progressed in FNMTC. In this work, an overview of genetic alteration related to syndromic and non-syndromic FNMTC is presented.
Assuntos
Mutação , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Polipose Adenomatosa do Colo/genética , Complexo de Carney/genética , Predisposição Genética para Doença , Síndrome do Hamartoma Múltiplo/genética , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Werner/genéticaAssuntos
Fibrilação Atrial , Complexo de Carney , Neoplasias Cardíacas , Mixoma , Complexo de Carney/diagnóstico por imagem , Complexo de Carney/genética , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Humanos , Mixoma/diagnóstico por imagem , Mixoma/cirurgiaRESUMO
RATIONALE: Carney complex (CNC) is a multiple neoplasia syndrome with autosomal dominant inheritance. CNC is characterized by the presence of myxomas, spotty skin pigmentation, and endocrine overactivity. No direct correlation has been established between disease-causing mutations and phenotype. PATIENT CONCERNS: A 16-year-old boy was admitted because of excessive weight gain over 3 years and purple striae for 1 year. Physical examination revealed Cushingoid features and spotty skin pigmentation on his face, lip, and sclera. DIAGNOSES: The patient was diagnosed as Carney complex. INTERVENTIONS: the patient underwent right adrenalectomy and partial adrenalectomy of the left adrenal gland. OUTCOME: Results of imaging showed bilateral adrenal nodular hyperplasia, multiple microcalcifications of the bilateral testes, and compression fracture of the thoracolumbar spine. Histopathological results confirmed multiple pigmented nodules in the adrenal glands. DNA sequencing revealed a nonsense mutation in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A; c.205Câ>âT). After the second adrenalectomy, the Cushingoid features disappeared, and cortisol levels returned to normal. LESSONS: Carney complex is a rare disease that lacks consistent genotype-phenotype correlations. Our patient, who carried a germline PRKAR1A nonsense mutation (c.205Câ>âT), clinical features included spotty skin pigmentation, osteoporosis, and primary pigmented nodular adrenal disease. Adrenalectomy is the preferred treatment for Cushing syndrome due to primary pigmented nodular adrenal disease.
Assuntos
Complexo de Carney/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Mutação/genética , Adolescente , Adrenalectomia , Complexo de Carney/diagnóstico , Complexo de Carney/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
Adrenocortical tumours (ACT), which include adenomas, carcinomas and adrenal hyperplasia, may be associated with genetic syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, familial adenomatous polyposis and Carney complex. Genetic defects have been found to be responsible for the disease in most of these syndromes, allowing genetic counselling to affected patients and family members. Here, we summarize the clinical criteria of these hereditary syndromes and briefly describe the genetic alterations related to them. In addition, we discuss the involvement of various genetic defects in the development of sporadic adrenocortical tumours.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , Hiperplasia Suprarrenal Congênita/genética , Adenoma Adrenocortical/genética , Síndrome de Beckwith-Wiedemann/genética , Complexo de Carney/genética , Humanos , Síndrome de Li-Fraumeni/genética , Modelos Biológicos , Neoplasia Endócrina Múltipla Tipo 1/genética , Síndromes Neoplásicas Hereditárias/genéticaRESUMO
Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare form of bilateral adrenocortical hyperplasia that is inherited in an autosomal dominant manner and leads to ACTH-independent Cushing's syndrome (CS). PPNAD may be isolated or associated with Carney Complex (CNC). For the diagnosis of PPNAD and CNC, in addition to the hormonal and imaging tests, searching for PRKAR1A mutations may be recommended. The aims of the present study are to discuss the clinical and molecular findings of two Brazilian patients with ACTH-independent CS due to PPNAD and to show the diagnostic challenge CS represents in childhood. Description of two patients with CS and the many sequential steps for the diagnosis of PPNAD is provided. Sequencing analysis of all coding exons of PRKAR1A in the blood, frozen adrenal nodules (patients 1 and 2) and testicular tumor (patient 1) is performed. After several clinical and laboratory drawbacks that misled the diagnostic investigation in both patients, the diagnosis of PPNAD was finally established and confirmed through pathology and molecular studies. In patient 1, sequencing of PRKAR1A gene revealed a novel heterozygous 10-bp deletion in exon 3, present in his blood, adrenal gland and testicular tumor. The etiologic diagnosis of endogenous CS in children is a challenge that requires expertise and a multidisciplinary collaboration for its prompt and correct management. Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group.