Loading...
Publication
Complexo de Carney: uma revisão narrativa
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 2.5 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
O Complexo de Carney (CNC), inicialmente denominado “complexo de mixomas,
manchas cutâneas pigmentadas e hiperatividade endócrina”, é uma síndrome endócrina
múltipla rara, caracterizada por uma ampla gama de manifestações clínicas, endócrinas
e não endócrinas, cujo diagnóstico continua a ser um desafio. Esta monografia visa
oferecer uma análise abrangente do conhecimento atual sobre o CNC, abordando as suas
características clínicas distintivas, a base genética subjacente, os critérios diagnósticos,
o diagnóstico diferencial com outras síndromes hereditárias, as opções terapêuticas
existentes, e os avanços mais recentes na investigação de novas abordagens terapêuticas.
A revisão dá especial ênfase às manifestações cutâneas, como a lentiginose e os mixomas
cutâneos, frequentemente responsáveis pelo reconhecimento precoce da síndrome, bem
como às manifestações cardíacas, nomeadamente os mixomas cardíacos, com impacto
significativo na morbilidade e mortalidade. É destacada a importância das mutações no
gene PRKAR1A na patogénese da síndrome e o seu papel no desenvolvimento de
neoplasias, benignas e malignas, que contribuem para a redução da esperança média de
vida destes pacientes. Sublinha-se ainda a relevância do rastreio clínico, do
acompanhamento multidisciplinar e do aconselhamento genético com rastreio familiar.
Apesar dos progressos desde a descrição inicial do CNC, há cerca de 40 anos, incluindo
a identificação do gene PRKAR1A, persistem desafios e questões em aberto. A abordagem
terapêutica continua a ser predominantemente cirúrgica, dada a ausência de terapias
sistémicas dirigidas às alterações moleculares. Esta revisão analisa ainda o panorama
atual da investigação em terapias inovadoras, destacando estudos recentes que exploram
o potencial de fármacos como a 8-Cl-adenosina e o celecoxib, bem como a compreensão
emergente das sinalopatias da via Gas-PKA como um contexto mais amplo para o CNC.
A complexidade desta via é vista como um desafio, mas também como uma oportunidade
para o desenvolvimento de terapias direcionadas, que atuem a diferentes níveis da
cascata de sinalização, em particular, na proteína cinase A (PKA) e nas suas subunidades.
Carney Complex (CNC), originally described as the “complex of myxomas, pigmented skin pigmentation, and endocrine overactivity”, is a rare multiple endocrine syndrome marked by a wide range of endocrine and non-endocrine manifestations, which continue to make diagnosis challenging. This monograph offers a comprehensive overview of current knowledge on CNC, covering its key clinical features, genetic basis, diagnostic criteria, differential diagnosis from other hereditary syndromes, available treatments, and recent advances in research into new therapeutic strategies. Special attention is given to cutaneous signs such as lentiginosis and cutaneous myxomas, which often lead to early diagnosis, as well as to cardiac involvement— especially cardiac myxomas—that significantly affect morbidity and mortality. The central role of PRKAR1A gene mutations in the disease’s pathogenesis is discussed, along with their contribution to the development of both benign and malignant tumours that impact life expectancy. The importance of clinical screening, multidisciplinary followup, and genetic counselling—including family screening—is also emphasised. Although significant progress has been made since CNC was first described nearly 40 years ago—particularly with the discovery of PRKAR1A—many questions and challenges remain. Current treatment is still largely surgical, as there are no effective systemic therapies targeting the underlying molecular alterations. This review also looks at the state of the art in innovative treatments, highlighting recent studies on the potential of drugs such as 8-Cl-adenosine and celecoxib, and examining the broader context of Gas– PKA signalling pathway disorders (signalopathies) in which CNC is included. While this signalling pathway is complex, it presents both a challenge and a promising target for future therapy development, especially approaches that act at different levels of the protein kinase A (PKA) signalling cascade and its subunits.
Carney Complex (CNC), originally described as the “complex of myxomas, pigmented skin pigmentation, and endocrine overactivity”, is a rare multiple endocrine syndrome marked by a wide range of endocrine and non-endocrine manifestations, which continue to make diagnosis challenging. This monograph offers a comprehensive overview of current knowledge on CNC, covering its key clinical features, genetic basis, diagnostic criteria, differential diagnosis from other hereditary syndromes, available treatments, and recent advances in research into new therapeutic strategies. Special attention is given to cutaneous signs such as lentiginosis and cutaneous myxomas, which often lead to early diagnosis, as well as to cardiac involvement— especially cardiac myxomas—that significantly affect morbidity and mortality. The central role of PRKAR1A gene mutations in the disease’s pathogenesis is discussed, along with their contribution to the development of both benign and malignant tumours that impact life expectancy. The importance of clinical screening, multidisciplinary followup, and genetic counselling—including family screening—is also emphasised. Although significant progress has been made since CNC was first described nearly 40 years ago—particularly with the discovery of PRKAR1A—many questions and challenges remain. Current treatment is still largely surgical, as there are no effective systemic therapies targeting the underlying molecular alterations. This review also looks at the state of the art in innovative treatments, highlighting recent studies on the potential of drugs such as 8-Cl-adenosine and celecoxib, and examining the broader context of Gas– PKA signalling pathway disorders (signalopathies) in which CNC is included. While this signalling pathway is complex, it presents both a challenge and a promising target for future therapy development, especially approaches that act at different levels of the protein kinase A (PKA) signalling cascade and its subunits.
Description
Keywords
Complexo de Carney Endocrinologia Genética Haploinsuficiência Pka Prkar1a