RESUMO
BACKGROUND: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in seizures, hemorrhage, recurrent headaches, and focal neurologic deficits. These CCMs can occur as sporadic or autosomal dominant conditions, although with incomplete penetrance and variable clinical expression. Three CCM loci have been identified, on chromosomes 7q21-22 (CCM1; Online Mendelian Inheritance in Man [OMIM] 116860), 7p13-15 (CCM2; OMIM 603284), and 3q25.2-27 (CCM3; OMIM 603285), and 3 genes have been cloned, KRIT1 on CCM1, MGC4607 on CCM2, and PDCD10 on CCM3. Mutations in KRIT1 account for more than 40% of CCMs. OBJECTIVE: To describe the results of a comprehensive evaluation of 5 Italian families affected with CCM. DESIGN: Clinical, magnetic resonance imaging, and KRIT1 gene analysis. SETTING: University academic teaching hospitals. PATIENTS: Fifteen patients with CCM diagnosed according to defined criteria and 45 at-risk, symptom-free relatives. RESULTS: Three novel and 2 described mutations were found in KRIT1. The families included 33 KRIT1 mutation carriers, 57.6% of whom had no symptoms. Magnetic resonance imaging revealed CCM lesions in 82.3% of symptom-free mutation carriers. CONCLUSIONS: The data confirm both incomplete clinical and neuroimaging penetrance in families with the KRIT1 mutation. This consideration is important in genetic counseling. Moreover, the data emphasize both the importance of magnetic resonance imaging in the diagnosis of CCM and the potential for DNA-based diagnosis to identify subjects at risk.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Imageamento por Ressonância Magnética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Doenças do Sistema Nervoso Central/etiologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Heterozigoto , Humanos , Itália , Proteína KRIT1 , Masculino , LinhagemRESUMO
MTHFR gene variants C677T and A1298C seem to be related to an increased risk of migraine. Folates' metabolism could play a role in the pathophysiology of migraine. We supplemented 16 children with migraine, hyperhomocysteinemia, and MTHFR polymorphisms with folic acid and obtained a resolution/reduction of migraine attacks. Although the mechanism leading to these effects has been not made clear, we believe that the use of folic acid needs further investigations in migraineurs with hyperhomocysteinemia and MTHFR variants. A randomized, double-blind, placebo controlled crossover trial is needed to support these findings.