Carney Complex

Introduction: Carney complex is a multiple neoplasia syndrome involving cardiac, endocrine, neural and cutaneous tumors with a variety of pigmented skin lesions. It has an autosomal dominant mode of inheritance. Approximately 7% of cardiac myxomas are related to the Carney complex. Myxomas that occur as part of the Carney complex affect both sexes with equal frequency. Cardiac myxomas with Carney complex are reported mostly in the left side of the heart and are less common on the right side. As per our review, this is the first reported case of Carney complex with right ventricle cardiac myxoma. Case presentation: We present a rare case of recurrent cardiac myxoma in a patient later diagnosed to have Carney complex. A 46-year-old Caucasian man with a history of thyroid hyperplasia came to out-patient cardiology department with new onset atrial fibrillation. A transthoracic echocardiogram revealed a right ventricular mass attached to his interventricular septum, which was later seen on a transesophageal echocardiogram and cardiac magnetic resonance imaging. He underwent resection of the ventricular mass which on pathology revealed myxoma. He later developed skin lesions, pituitary adenoma and Sertoli cell tumor suggesting Carney complex. Two years later he developed a new mass within his right atrium which was later resected.

Mitral annular calcification, endothelial dysfunction, carotid intima-media thickness and fetuin-A Mitral anüler kalsifikasyon, endotel disfonksiyonu, karotis intima-media kalınlığı ve fetuin-A Murat Ziyrek et al.; İstanbul-Turkey Effect of shisha vs. cigarette smoking on endothelial function by brachial artery duplex ultrasonography Brakiyal arter dubleks ultrasonografi ile, sigaraya karşılık nargile içmenin endotel fonksiyonuna etkisi Ghada Selim et al.; Cairo-Egypt Assessment of cardio-ankle vascular index in patients with cardiac syndrome-X Kardiyak sendrom -X hastalarında kalp-ayak bileği vasküler indeksinin değerlendirilmesi Ahmet Çağrı Aykan et al.; Trabzon, İstanbul-Turkey QT dispersion, sex hormones and insulin in young women with polycystic ovary syndrome Polikistik over sendromlu genç kadınlarda QT dispersiyonu ile gonadal hormonlar ve insülin Emine Gazi et al.; Çanakkale-Turkey Predictors of functional capacity in younger and elderly chronic heart failure patients Kronik kalp yetersizliği olan genç ve yaşlı hastalarda fonksiyonel kapasitenin öngördürücüleri Nihat Polat et al.; İstanbul-Turkey Subclinical left ventricular dysfunction in women with polycystic ovary syndrome Polikistik over sendromlu kadınlarda subklinik sol ventrikül disfonksiyonu Ercan Erdoğan et al.; İstanbul-Turkey Adiponectin , epicardial adipose tissue thickness and low cardiac risk in Gilbert`s syndrome Gilbert sendromunda epikardiyal yağ doku kalınlığı ve adiponektin ile düşük kardiyak risk Erkan Cüre et al.; Rize-Turkey Assessment of epileptic seizures by pre-seizure heart rate variability Epileptik nöbetlerin kriz öncesi kalp hızı değişkenliği ile değerlendirilmesi Soroor Behbahani et al.; Tehran-Iran; Coimbra-Portugal Bilimsel Mektuplar / Scientific Letter The effects of antedgrade cerebral perfusion on postoperative outcome in neonatal and infant Yenidoğan ve infantta erken postoperatif dönemde antegrad serebral perfüzyonun etkileri Ali Rıza Karacı et al.; İstanbul-Turkey

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

A mellékvesekéreg-carcinoma ritka, rossz prognózisú daganat. Döntően sporadikus előfordulású, de ismertek nagyon ritka öröklődő formái is, amelyek a patogenezis megértésében nagy segítséget nyújtanak. A mellékvesekéreg-daganatokra hajlamosító öröklődő szindrómák közé tartozik a Li-Fraumeni-szindróma, a Beckwith-Wiedemann-szindróma, a familiáris adenomatosus polyposis, illetve a döntően benignus daganatokkal társuló multiplex endokrin neoplasia 1-es típusa (MEN1), Carney-komplex és McCune-Albright-szindróma. A mellékvesekéreg-daganatok patogenezisében szereplő főbb mechanizmusok közé tartozik az inzulinszerű növekedési faktor-2 fokozott expressziója, a Wnt/β-katenin és a cAMP-proteinkináz-A jelátviteli utak aktivációja, valamint a p53 és MEN1 gének mutációi. A mellékvesekéreg-carcinoma kezelésében a gyógyszeres lehetőségek meglehetősen korlátozottak. Az utóbbi évek molekuláris-bioinformatikai kutatásai számos eddig ismeretlen patogenetikai út szerepét vetették fel, amelyek új gyógyszeres támadáspontok lehetőségét is jelenthetik. E tanulmányban a szerzők az öröklődő daganatszindrómák patogenezisét, a sporadikus daganatokban észlelt eltéréseket és a legújabb molekuláris-bioinformatikai eredményeket ismertetik.

Resumen El angiomixoma superficial (AS) es una neoplasia benigna cutánea infrecuente que fue descrita por primera vez por Allen y colaboradores en 1988. Presentamos el primer caso publicado en la literatura médica de angiomixoma superficial localizado en la región parotídea, destacando la importancia de distinguir esta entidad de otras lesiones que pueden aparecer en esta área, como neoplasias cutáneas, tumores o quistes. Así mismo hacemos hincapié en la necesidad de descartar la asociación con el complejo Carney ante el diagnóstico de este tipo de lesiones.

Carney Complex (CNC) is a rare autosomal dominant syndrome, characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas, and multiple endocrine tumors. The disease is caused by inactivating mutations or large deletions of the PRKAR1A gene located at 17q22-24 coding for the regulatory subunit type I alpha of protein kinase A (PKA) gene. Most recently, components of the complex have been associated with defects of other PKA subunits, such as the catalytic subunits PRKACA (adrenal hyperplasia) and PRKACB (pigmented spots, myxomas, pituitary adenomas). In this report, we review CNC, its clinical features, diagnosis, treatment, and molecular etiology including PRKAR1A mutations and the newest on PRKACA and PRKACB defects especially as they pertain to adrenal tumors and Cushing's syndrome.

Solitary myxomas without other manifestations of Carney’s complex usually arise within the skeletal or cardiac muscles, and less commonly in the intestine, pelvis and subcutis, and very rarely in the skin. Solitary cutaneous myxomas (SCM), more descriptively called solitary superficial angiomyxomas, are uncommon tumours having characteristic histological findings. They occur most commonly on the trunk, leg, head and neck, and more rarely at acral sites of adults. They are characterized
histologically by a well-defined, hypocellular, myxoid tumour with many vascular components in the dermis or subcutaneous fat. We report a case of solitary skin myxoma sitting on the scalp of a young child.

Carney complex (CNC) is a multiple endocrine neoplasia (MEN) syndrome characterized by lentigines, cardiac myxomas and tumors, including primary pigmented adrenocortical disease (PPNAD). In the present report we review the main clinical manifestations of this disorder. We also discuss some of the newest molecular information regarding CNC. The complex has been mapped to 2p16 and 17q22-24, and a third locus appears likely. The gene coding for the protein kinase A (PKA) type I-a regulatory subunit (RIa), PRKAR1A, had been mapped to 17q. Cloning of the PRKAR1A genomic structure and its sequencing showed mutations in CNC patients. So far, among 57 kindreds, PRKAR1A mutations have been found in 28. In almost all the mutations, the sequence change is predicted to lead to a premature stop codon; 1 mutation altered the initiator ATG codon. Analysis of mRNA transcripts in patient lymphocytes treated with cycloheximide showed that mutant mRNAs containing a premature stop codon were degraded, due to nonsense-mediated mRNA decay-the predicted mtPRKAR1A protein products were absent in these cells. In CNC tumors, PKA activity showed increased stimulation by cAMP, whereas PKA activity ratio was decreased. To date, mutations in the PRKAR1A gene have been described in CNC patients and in some sporadic endocrine tumors. LOH of the normal allele and increased PKA activity in response to cAMP are found in these tumors, suggesting that normal PRKAR1A (largely responsible for PKA type I activity) is implicated more widely in endocrine tumorigenesis. CNC is the first human disease caused by mutations of one of the subunits of the PKA holoenzyme, a critical component of numerous cellular signaling systems.

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.17711G.A) were located in exons 3 to 5 and introns 2 to 3, and all led to a nonsense 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.

Context: Carney complex is a genetically heterogenous multiple neoplasia syndrome. Adrenal cortical carcinoma is a rare malignancy with a poor prognosis that is not recognized to be associated with this syndrome. Objective: We report a 22-yr-old female presenting with Carney complex who developed adrenal carcinoma. The response to adjunctive therapy is also described. Methods: We performed a detailed pathology review of the adrenal tumor to examine morphologic changes, Ki-67 labeling, and p53 expression. We also performed genetic testing of candidate genes and describe the response to radiation and kinase inhibition therapy. Results: The patient presented with an 8.5-cm adrenal mass with a MIB-1 labeling index of 20% and unequivocal angioinvasion classified as a T3NXM0 carcinoma. The nontumorous adrenal cortex revealed characteristic features of primary pigmented nodular adrenocortical disease. Genetic analysis revealed a novel PRKAR1 frame shift mutation resulting in a premature stop codon and a heterozygous p53 polymorphic substitution previously noted in other solid carcinomas. Disease recurrence in the liver showed partial response to combined stereotactic radiotherapy and sorafenib multikinase inhibition. Conclusion: This represents an initial characterization of a malignancy among patients with Carney complex. Our findings have implications for disease surveillance and management of individuals with this genetic syndrome.

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Introduction: Carney complex is a multiple neoplasia syndrome involving cardiac, endocrine, neural and cutaneous tumors with a variety of pigmented skin lesions. It has an autosomal dominant mode of inheritance. Approximately 7% of cardiac myxomas are related to the Carney complex. Myxomas that occur as part of the Carney complex affect both sexes with equal frequency. Cardiac myxomas with Carney complex are reported mostly in the left side of the heart and are less common on the right side. As per our review, this is the first reported case of Carney complex with right ventricle cardiac myxoma. Case presentation: We present a rare case of recurrent cardiac myxoma in a patient later diagnosed to have Carney complex. A 46-year-old Caucasian man with a history of thyroid hyperplasia came to outpatient cardiology department with new onset atrial fibrillation. A transthoracic echocardiogram revealed a right ventricular mass attached to his interventricular septum, which was later seen on a transesophageal echocardiogram and cardiac magnetic resonance imaging. He underwent resection of the ventricular mass which on pathology revealed myxoma. He later developed skin lesions, pituitary adenoma and Sertoli cell tumor suggesting Carney complex. Two years later he developed a new mass within his right atrium which was later resected. Conclusions: Carney complex is a rare autosomal dominant disease with variable penetrance. Since it involves multiple organs, patients diagnosed with Carney complex should undergo serial endocrine workup, neural assessments, echocardiograms and testicular ultrasounds. Of the total number of cases of Carney complex, 65% are linked to PRKAR1A gene mutation. It is important for clinicians to be cognizant of a link between cardiac myxoma and Carney complex. The use of multi-imaging modalities allows better delineation of the mass before planned resection. Carney complex-related cardiac myxoma comprises 7% of all cardiac myxomas. Right ventricular cardiac myxomas are rare. This case report is the first to describe right ventricular myxoma with Carney complex.

Myxomas of the ear are extremely uncommon, especially in young children. A 23-month-old girl born to a family with known Carney complex, a condition that predisposes to multiple myxomas, presented with a large, cauliflower-like mass located on the back of her right ear. Histopathologically, the lesion was composed of scattered spindle-shaped or stellate cells with abundant associated mucin and a very sparse inflammatory infiltrate containing lymphocytes and neutrophils. The patient was a carrier of a protein kinase A regulatory subunit 1A (PRKAR1A) mutation; PRKAR1A mutations cause Carney complex in most patients with this rare disorder. This is the earliest presentation of an ear lobe myxoma reported in the literature.

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 ACTHindependent 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.

pituitary mass (Fig. 1b). Her mean serum GH concentration on the GH day curve remained less than 2 ng/ml and serum IGF-1 stayed in the age-adjusted reference range. Acromegaly is associated with a mortality of about 2-3 times that of the background population, which is predominantly secondary to cardiomyopathy and cerebrovascular disease. 5 Acromegalic cardiomyopathy occurs most often in older acromegalics with longer duration of disease and has been described as occurring in three stages. In early disease, there is cardiac hypertrophy and increased systolic output. In the second phase, hypertrophy is worsened, diastolic dysfunction develops and systolic dysfunction occurs on effort. The last stage, as was present in our patient, consists of systolic dysfunction at rest and dilated cardiomyopathy. 1 Chronic cardiac dysfunction has been shown to reverse or improve with correction of GH hypersecretion. Two previous cases have been described where biochemical cure of acromegaly was demonstrated after pituitary apoplexy. The first case demonstrated haemorrhagic infarction of a GH-secreting macroadenoma following gadopentetate dimeglumine (Gd-DTPA) administration for contrast-enhanced MRI. 3 Within days, GH levels suppressed normally with glucose challenge. The second case report described pituitary infarction following gastrointestinal bleeding from a peptic ulcer. Again, infarction resulted in cure of acromegaly. 4 However, this is the first case report of spontaneous recovery of severe acromegalic cardiomyopathy as a result of acute hypotensive infarction of the somatotroph adenoma. The hypotension resulted from pump failure secondary to decompensated CCF. The infarction resulted in a marked and rapid reduction of GH secretion and normalization of serum IGF-1 levels to a degree that is epidemiologically associated with normal mortality. 5 The patient also showed marked clinical improvement with complete normalization of her ejection fraction and resolution of all symptoms. It can be said that a complication of acromegaly resulted in cure of the disease itself.

Although infrequently seen, the management of cancer during pregnancy can be difficult for patients, their families and physicians. The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 26-yearold woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in chronic phase by using only leukapheresis. She was treated with leukapheresis until her delivery at 36 weeks of gestation. The procedure was without significant adverse effects on the patient or fetus. We applied a total of 15 leukapheresis treatments throughout the pregnancy. The patient gave birth vaginally to a healthy 2800 g boy at 36 weeks of gestation. We conclude that leukapheresis may provide an alternative treatment to chemotherapy, α-interferon or imatinib in pregnant patients with CML, particularly with concern over their potential teratogenic and other adverse effects.

Carney complex is a very rare multiple neoplasia syndrome with cardiac, cutaneous, and neural tumours with a variety of pigmented lesion of skin. We are reporting a rare case of carney complex in which left atrial myxoma with superficial angiomyxoma, giant cell tumour of bone and ...

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Carney complex is a very rare multiple neoplasia syndrome with cardiac, cutaneous, and neural tumours with a variety of pigmented lesion of skin. We are reporting a rare case of carney complex in which left atrial myxoma with superficial angiomyxoma, giant cell tumour of bone and lentigines showed a unique association. This patient underwent successful surgical excision of left atrial myxoma under cardiopulmonary bypass.

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.