RESUMO
Angiomas cavernosos ou simplesmente cavernomas são má-formações vasculares congênitas raras, acometendo 0,5% da população, podendo apresentar-se sob as formas esporádica e familiar. Quando acomete indivíduos de uma mesma família é denominado cavernomatose cerebralfamiliar (CCF), tendo sua transmissão autossômica dominante com penetração incompleta associada a mutações no locus CCF1 no cromossomo 7. A CCF acomete, em geral, vários indivíduos de uma mesma família, grande parte desses com lesões múltiplas, algumas vezes até com aparecimento tardio. Essas características apontam para a necessidade de uma abordagem diferenciada de indivíduos com cavernomas múltiplos esuas famílias. Relatamos o caso de um paciente de 5 anos de idade, com três cavernomas cerebrais, e sua irmã de 3 anos, com outra lesão. Discutimos o tratamento e o seguimento deles e de sua família, propondo sugestões para a abordagem da CCF.
Cavernous hemangiomas or simply cavernomas are rare congenital vascular malformations mostly located in the central nervous system, which prevalence is close to 0.5% in the general population.They can present itself either as a sporadic case or in a familial form. The familial form is called familial cerebral cavernomatosis (FCC), having an autossomical dominant inheritance with incomplete penetration associated to mutations of the CCF1 locus on chromossome 7. In general, CCF is present in many individuals of a given family, mostly with multiple lesions, some of those even with a late onset. These characteristics imply the need of a special approach towards diagnosis and treatment of patients with multiple cavernomas and their families. We report the case of a 5 year-old boy with three cerebral cavernomas and of his 3 year-old sisterwith another lesion. The treatment and the management of familiar forms of cavernomas are discussed.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Hemangioma Cavernoso/cirurgia , Hemangioma Cavernoso/genética , Hemangioma Cavernoso/terapiaRESUMO
OBJECTIVE: To determine with greater precision the map location of the locus associated with familial cavernous hemangiomas. BACKGROUND: Cavernous malformations of the brain are a significant cause of seizures, progressive or apoplectic neurologic deficit, and headache. Prevalence estimates from autopsy series vary from 0.39 to 0.9%. This disorder (OMIM #116860) can be inherited as an autosomal dominant trait with variable penetrance. Linkage to markers on the long arm of chromosome 7 was recently reported in separate reports in three apparently unrelated Hispanic kindreds as well as in two kindreds of non-Hispanic descent. DESIGN/METHODS: We examined clinically, by MRI scanning, and by pathologic examination of surgical specimens, members of four large Mexican-American families segregating cavernous hemangiomas of the brain. Linkage analysis was performed with use of blood specimens from morphologically proven cases. Two-point linkage analysis was performed with the MLINK program of the LINKAGE package. Multipoint analysis was performed between two markers and the disease locus with LINKMAP in the FASTLINKAGE package. Allele frequencies were set as described by the Genome Database (GDB). Maximum penetrance for the disease allele was set to 0.75. RESULTS: The highest lod score was observed for marker D7S652 with Zmax = 6.66 at theta(max) = 0.00. Multipoint LOD score analysis placed the disease locus in the 11 cM interval between markers D7S630 and D7S527 with Zmax = 9.19. Haplotype analysis is in agreement with the placement of the disease gene between D7S630 and D7S527 and further shows a minimal shared region within this interval, indicating a founder effect in the establishment of the mutation in these families. CONCLUSIONS: We confirmed the linkage of cavernous hemangioma to markers on the long arm of chromosome 7q, and the estimate of the map location has been refined to a region of shared haplotype between markers D7S630 and D7S527 in four Mexican-American families who may be descended from a common ancestor in Sonora County, Mexico.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 7 , Ligação Genética , Hemangioma Cavernoso/genética , Hispânico ou Latino , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Criança , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/etnologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Convulsões/etiologia , Hemorragia Subaracnóidea/etiologiaRESUMO
Cavernous angioma is a vascular malformation that affect 0.5 to 0.7% of the population making up 8 to 15% of cerebrovascular malformations. It is the second vascular malformation in frequency of the central nervous system, supplanted only by classic arteriovenous malformation. It may occur in two forms: a sporadic form characterized by isolated lesions: and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance with high penetrance and varied expressivity in the proportion M1:F1. Symptoms related to cavernous angioma are seizures, headache or progressive neurologic deficit. The authors present a Chinese family with familial cavernous angioma. Manifestations of the disease occurred in three generations affecting only females. Clinical, neuroimage, pathological, natural course and genetical aspects of the disease are discussed.
Assuntos
Neoplasias Encefálicas/genética , Tronco Encefálico , Hemangioma Cavernoso/genética , Malformações Arteriovenosas Intracranianas/genética , Adulto , Neoplasias Encefálicas/diagnóstico , Tronco Encefálico/diagnóstico por imagem , Criança , Feminino , Hemangioma Cavernoso/diagnóstico , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico , Pessoa de Meia-Idade , Linhagem , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/genética , Tomografia Computadorizada por Raios XRESUMO
O angioma cavernoso ou cavernoma é malformaçao vascular que acomete O,5 a O,7 por cento da populaçao, perfazendo 8 a 15 por cento de todas as malformaçoes vasculares do neuroeixo, sendo a segunda malformaçao mais frequente do sistema nervoso central. É menos frequente apenas que a malformaçao arteriovenosa clásssica. Pode ocorrer sob duas formas: esporádica e familiar. Esta última é mais frequentemente associada a lesoes múltiplas e com modo de transmissao autossômico dominante com alta penetrância e expressividade variada na proporçao M1:F1. Os cavernomas manifestam-se mais frequentemente por crises convulsivas, cefaléia ou déficit neurológico progressivo. Apresentamos uma família de origem chinesa com diagnóstico de angioma cavernoso familiar ocorrendo em três geraçoes e incidindo apenas no sexo feminino. Sao discutidos aspectos clínicos, de diagnóstico por imagem, patológicos, de evoluçao natural e genéticos da doença.