A síndrome do complexo de Carney-trismo-pseudocamptodactilia é uma síndrome genética rara do coração-mão caracterizada por manifestações típicas do complexo de Carney (pigmentação manchada da pele, mixomas cardíacos e cutâneos familiares e endocrinopatia) associada a trismo e artrogripose distal (apresentando-se como contração involuntária das articulações interfalângicas distais e proximais das mãos, evidente apenas na dorsiflexão do punho e contraturas semelhantes dos membros inferiores, produzindo deformidades nos pés).
Introdução
O que você precisa saber de cara
A síndrome do complexo de Carney-trismo-pseudocamptodactilia é uma síndrome genética rara do coração-mão caracterizada por manifestações típicas do complexo de Carney (pigmentação manchada da pele, mixomas cardíacos e cutâneos familiares e endocrinopatia) associada a trismo e artrogripose distal (apresentando-se como contração involuntária das articulações interfalângicas distais e proximais das mãos, evidente apenas na dorsiflexão do punho e contraturas semelhantes dos membros inferiores, produzindo deformidades nos pés).
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 4 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
1 gene identificado com associação a esta condição. Padrão de herança: Not applicable.
Muscle contraction
Cytoplasm, myofibril
Carney complex variant
Carney complex is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. Familial cardiac myxomas are associated with spotty pigmentation of the skin and other phenotypes, including primary pigmented nodular adrenocortical dysplasia, extracardiac (frequently cutaneous) myxomas, schwannomas, and pituitary, thyroid, testicular, bone, ovarian, and breast tumors. Cardiac myxomas do not develop in all patients with the Carney complex, but affected patients have at least two features of the complex or one feature and a clinically significant family history.
Variantes genéticas (ClinVar)
41 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 12 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
1 via biológica associada aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Síndrome do complexo de Carney-trismus-pseudocamptodactilia
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
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Whole-body exposure to ionizing radiation can lead to cellular DNA damage to bone marrow (BM), causing lethal hematopoietic acute radiation syndrome (H-ARS). Extracellular vesicles (EVs) from human BM-derived mesenchymal stromal cells were primed with CRX-527 (CRX), a synthetic TLR4 agonist, characterized and tested as a radiomitigator therapy. Using a xenogeneic H-ARS mouse model, a single in vivo treatment with CRX-EVs administered 4 or 24 hours after lethal irradiation significantly improved weight loss, clinical scores and prolonged survival compared to control treatments. Ex vivo generation of CRX-EV educated monocytes (CRX-EEMos) were also effective in a H-ARS model when administered 24 hours after lethal irradiation. CRX-EVs or CRX-EEMos significantly promoted hematopoiesis in BM and potentially the spleen, leading to restoration of peripheral complete blood counts. CRX-EEMos showed increased gene expression of IL-6 and IL-10: enriched for PD-L1 but low for CD16 in CD14-expressing monocytes. Antisense inhibition of Let-7 microRNAs in CRX-EEMos suppressed IL-10 gene expression and protein secretion, implicating a novel role for Let-7 in radioprotection. CRX-EVs can effectively treat H-ARS by increasing the secretion of anti-inflammatory molecules while stimulating monocytes to promote hematopoiesis in BM. The potential for large-scale production of CRX-EVs as an "off-the-shelf" treatment for H-ARS makes them a potential medical countermeasure for radiological and nuclear threats.
cAMP/PKA signaling in endocrine hypertension: genetic mechanisms and pathophysiological insights.
The cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway plays a central role in adrenal function, steroidogenesis, and blood pressure regulation. Increasing evidence suggests that dysregulation of this pathway contributes to several forms of hypertension, both endocrine and non-endocrine. A growing number of germline and somatic alterations affecting components of the cAMP/PKA axis have been implicated as key drivers of hypertensive disorders. Among these, activating pathogenic variants (PV) in GNAS, which encodes the stimulatory G protein α-subunit (Gsα) responsible for cAMP production, have been linked to cortisol excess. Mosaic GNAS PV cause McCune-Albright syndrome, which may present with ACTH-independent Cushing syndrome, while somatic GNAS PV have been identified in cortisol-producing adrenal adenomas. Germline inactivating variants in PRKAR1A are associated with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD). Furthermore, germline alterations in phosphodiesterases such as PDE11A and PDE8B, which impair cAMP degradation, have been associated with Cushing syndrome and micronodular adrenal hyperplasia. Somatic activating PV in PRKACA, the gene encoding the catalytic subunit of PKA, have also been described in cortisol-producing adenomas. In primary aldosteronism, recent studies-including data from our group-suggest that germline variants in PDE2A and PDE3B may contribute to bilateral adrenal hyperplasia and autonomous aldosterone production by modulating intracellular cAMP levels. Additionally, gain-of-function PV in PDE3A have been associated with a familial form of salt-independent hypertension characterized by enhanced PKA signaling and vascular remodeling. This expanding body of evidence underscores the critical role of the cAMP/PKA pathway in the pathophysiology of distinct hypertensive phenotypes and highlights novel molecular mechanisms and potential therapeutic targets that merit further investigation.
A urologic manifestation of carney complex: Bilateral Sertoli tumors and scrotal myxoma in an adolescent male.
Carney complex (CNC) is a rare tumor syndrome caused by mutations in the PRKAR1A gene, characterized by endocrine tumors, cardiac and cutaneous myxomas, pigmented lesions, and testicular tumors. One to two thirds of affected males develop large cell calcifying Sertoli cell tumors (LCCSCTs), with rare involvement of scrotal soft tissues. We present a case of CNC in an adolescent male with bilateral LCCSCTs and a very large scrotal myxoma, resulting in azoospermia and pain requiring surgical management. This report highlights the urologic manifestations of CNC and outlines appropriate evaluation, treatment, and surveillance strategies relevant to pediatric and adolescent urologic practice.
Endosome maturation is orchestrated by inside-out proton signaling through a Na+/H+ exchanger and pH-dependent Rab GTPase cycling.
Endosome maturation requires lumen acidification. Is progressive lumen acidification sensed by cytosolic-side molecules driving maturation? We show here that proton efflux through the endosomal Na+/H+ Exchanger (NHE6) activates the late endosome master regulator Rab7. Importantly, NHE6 is mutated in the childhood neurologic disorder Christianson Syndrome. We demonstrate that NHE6 interacts with the Rab7 GTPase-activating protein (GAP) TBC1D5 in a complex with Rab7 on the late endosome. This interaction and proton efflux are both required for Rab7 activation. TBC1D5 is potently inactivated with decreasing pH. A conserved histidine in the TBC1D5 GAP domain mediates pH-dependence. Furthermore, we show that neurons from mice engineered with a selective defect in NHE6 proton efflux exhibit blocked endosome maturation and disrupted Rab7 GTP-GDP cycling. In addition, knock-down of TBC1D5, thereby reducing Rab7 GAP activity, in NHE6 mutant neurons rescues Rab7 GTP-GDP cycling and endosome maturation. Finally, we present a biophysical model of proton signaling through acidic pH microdomains within the NHE6-TBC1D5-Rab7 protein complex upon endosome acidification. In conclusion, our studies provide evidence supporting a mechanism involving "inside-out" proton signaling, whereby lumen acidification drives endosome maturation through pH-dependent Rab GTPase cycling. Failure in this mechanism may have broad impact in neurodegenerative disease.
Case Reports: Exploring the Varied Presentations and Clinical Features of Carney Complex, A Detailed Report on Three Distinct Cases.
Carney Complex (CNC) is a rare genetic disorder characterized by multiple endocrine and nonendocrine neoplasms, primarily driven by mutations in the PRKAR1A gene. This study explores the clinical heterogeneity in CNC patients, with a focus on adrenal and extra adrenal involvement and its impact on patient outcomes. We present three pediatric cases with unique clinical manifestations. Case 1: A 12-year-old female with ACTH-independent cyclic Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The patient's condition progressed, leading to complications such as obesity, depression, and short stature, ultimately requiring bilateral adrenalectomy. Case 2: A 9-year-old male presented with an intranasal osteochondromyxoma and a large cell calcifying sertoli cell tumor. In the followup he developed hypocortisolism secondary to ACTH deficiency, with further complications including central precocious puberty and a growth hormone-secreting pituitary adenoma. Case 3: A 12-year-old female with adrenal insufficiency due to ACTH deficiency, complicated by a pituitary adenoma and a recurrent cardiac myxoma. Over time, the patient developed ACTH-independent Cushing syndrome secondary to PPNAD, necessitating bilateral adrenalectomy. Multiple fusiform aneurysms were also discovered after the recurrence of atrial myxoma. All cases highlight the absence of a consistent genotype-phenotype correlation in CNC, emphasizing the need for individualized management strategies. The findings underscore the complexity of diagnosing and treating CNC, particularly in pediatric populations, and call for further research into the underlying molecular mechanisms to develop more targeted therapies.
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Children (Basel, Switzerland)Carney complex- why thorough medical history taking is so important - report of three cases and review of the literature.
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Annals of oncology : official journal of the European Society for Medical OncologyA Novel Missense PRKAR1A Variant Causes Carney Complex.
Endocrinology and metabolism (Seoul, Korea)Efficacy of aromatase inhibitor therapy in a case with large cell calcifying Sertoli cell tumour-associated prepubertal gynaecomastia.
Journal of pediatric endocrinology & metabolism : JPEMLoss of endosomal exchanger NHE6 leads to pathological changes in tau in human neurons.
Stem cell reportsA Rare Case of Multiple Gastrointestinal Stromal Tumors Coexisting with a Rectal Adenocarcinoma in a Patient with Attenuated Familial Adenomatous Polyposis Syndrome and a Mini Review of the Literature.
Medicina (Kaunas, Lithuania)Unilateral or bilateral adrenalectomy in PPNAD: six cases from a single family followed up over 40 years.
EndocrineMalignant Melanotic Nerve Sheath Tumors: A Review of Clinicopathologic and Molecular Characteristics.
Journal of microscopy and ultrastructureA Rare Case of Horseshoe Kidney With Multiple Atrial Myxomas Presenting as Cerebrovascular Accident.
CureusDefining and Assessing the Syndrome of Moral Injury: Initial Findings of the Moral Injury Outcome Scale Consortium.
Frontiers in psychiatryConjunctival myxoma masquerading as conjunctival lymphoma: A case report.
International journal of surgery case reportsMalignant psammomatous melanotic schwannoma mimicking adrenal cyst: case report.
Annals of pediatric surgeryLaparoscopic resection for recurrent gastrointestinal stromal tumors and paraganglioma in a patient with Carney-Stratakis syndrome: A case report.
Asian journal of endoscopic surgeryCarney complex with multiple breast tumours including breast cancer: a case report.
Oxford medical case reportsComparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes.
BiomedicinesPhenotypic Variability in a Family with Carney Complex Accompanied by a Novel Mutation Involving PRKAR1A.
The Tohoku journal of experimental medicineMultiplex Detection of Antibody Landscapes to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Influenza/Common Human Coronaviruses Following Vaccination or Infection With SARS-CoV-2 and Influenza.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of AmericaGenetic Alterations in Benign Adrenal Tumors.
BiomedicinesSteroidogenic Factor-1 Lineage Origin of Skin Lesions in Carney Complex Syndrome.
The Journal of investigative dermatologyAcute phase protein response and changes in lipoprotein particle size in dogs with systemic inflammatory response syndrome.
Journal of veterinary internal medicineMolecular genetic testing in the management of pituitary disease.
Clinical endocrinologyCirculating osteopontin mediates acute kidney injury-induced respiratory failure.
Nature reviews. NephrologyInnate lymphoid cells and COVID-19 severity in SARS-CoV-2 infection.
eLifeConjunctival myxoid stromal tumor of the palpebral conjunctiva: A case report.
American journal of ophthalmology case reportsHuriez syndrome: Additional pathogenic variants supporting allelism to SMARCAD syndrome.
American journal of medical genetics. Part AThorahcic SMARCA4-deficient undifferentiated tumors with ganglioneuroma and enchondroma: implications for SLC7A11 and ARID1A expression: a case report.
Diagnostic pathologyA novel 8.57-kb deletion of the upstream region of PRKAR1A in a family with Carney complex.
Molecular genetics & genomic medicineSDHA Germline Variants in Adult Patients With SDHA-Mutant Gastrointestinal Stromal Tumor.
Frontiers in oncologyCarney Complex Complicated with Primary Pigmented Nodular Adrenocortical Disease without Cushing's Syndrome Recurrence for Five Years after Unilateral Adrenalectomy.
Internal medicine (Tokyo, Japan)Novel CD63-PRKCB fusion in a case of pigmented epithelioid melanocytoma.
Pediatric dermatologyDevelopment of a Manually Operated Communication System (MOCS) for patients in intensive care units.
Augmentative and alternative communication (Baltimore, Md. : 1985)Channelopathy of Dravet Syndrome and Potential Neuroprotective Effects of Cannabidiol.
Journal of central nervous system diseaseA review of fenfluramine for the treatment of Dravet syndrome patients.
Current research in pharmacology and drug discoveryA clinicopathologic analysis of 54 cases of cutaneous myxoma.
Human pathologyEarly lysosome defects precede neurodegeneration with amyloid-β and tau aggregation in NHE6-null rat brain.
Brain : a journal of neurologyLarge Cell Calcifying Sertoli Cell Tumor: A Clinicopathologic Study of 18 Cases With Comprehensive Review of the Literature and Reappraisal of Prognostic Features.
The American journal of surgical pathologyValidated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
The Journal of pathologyBloody nipple discharge in Carney complex: A case report.
The breast journalSuperficial angiomyxoma of the breast in a 16-year-old girl without carney's complex: A case report.
The breast journalProtein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.
The Journal of clinical investigationCarney's triad in an adult male from a tertiary care center in India: a case report.
Journal of medical case reportsDermatologic manifestations of pediatric cardiovascular diseases: Skin as a reflection of the heart.
Pediatric dermatologyCase Report: An Atypical Case of Carney Complex.
The American journal of case reportsBilateral Adrenal Hyperplasia: Pathogenesis and Treatment.
BiomedicinesGαs-Protein Kinase A (PKA) Pathway Signalopathies: The Emerging Genetic Landscape and Therapeutic Potential of Human Diseases Driven by Aberrant Gαs-PKA Signaling.
Pharmacological reviewsPeutz-Jeghers syndrome: Skin manifestations and endocrine anomalies (Review).
Experimental and therapeutic medicineDiagnosis of Carney complex following multiple recurrent cardiac myxomas.
General thoracic and cardiovascular surgeryDermatological and endocrine elements in Carney complex (Review).
Experimental and therapeutic medicineAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Extracellular vesicles from mesenchymal stromal cells primed with synthetic toll-like receptor 4 agonists treat hematopoietic acute radiation syndrome.
- cAMP/PKA signaling in endocrine hypertension: genetic mechanisms and pathophysiological insights.
- A urologic manifestation of carney complex: Bilateral Sertoli tumors and scrotal myxoma in an adolescent male.
- Endosome maturation is orchestrated by inside-out proton signaling through a Na+/H+ exchanger and pH-dependent Rab GTPase cycling.
- Case Reports: Exploring the Varied Presentations and Clinical Features of Carney Complex, A Detailed Report on Three Distinct Cases.
- Molecular characterization of large cell calcifying sertoli cell tumors: A multi-institutional study of 6 benign and 2 malignant tumors.
- [Rare forms of hereditary endocrine neoplasia: co-existence of pituitary adenoma and pheochromocytoma/paraganglioma].
- Pituitary Tumorigenesis-Implications for Management.
- Unusual Findings in a Patient With Carney Complex due to a Novel PRKAR1A Mutation.
- The Spectrum of Familial Pituitary Neuroendocrine Tumors.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:319340(Orphanet)
- OMIM OMIM:608837(OMIM)
- MONDO:0012137(MONDO)
- GARD:17448(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q105544026(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar