Expansión anormal de hexanucleótido en gen C9orf72 en una familia con demencia frontotemporal y cuadros asociados / Abnormal expansion of C9orf72 gene in familial frontotemporal dementia

Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND) may share similar pathogenic mechanisms. An abnormal hexanucleotide expansion in C9orf72 gene is the most common genetic abnormality of these conditions and explains their concurrence in the same family. We report a 77-year-old female presenting with non-fluent aphasia leading to mutism and a mild Parkinsonism. A magnetic resonance imaging showed a severe atrophy of frontal and temporal lobes. Several family members of the patient suffered of atypical Parkinsonism, lateral amyotrophic sclerosis and dementia. We identified an abnormal hexanucleotide expansion in the C9orf72 gene in the proband. To the extent of our knowledge, this is the first time that this diagnosis is confirmed in our country. The knowledge of the genetic basis of neuro degenerative disorders improves diagnosis and opens expectatives for future treatments of these disabling conditions.

C9ORF72 and the FTD-ALS spectrum: a systematic review of neuroimaging studies / Mutações no Cromossoma 9 e o Espectro DFT-ELA: revisão sistemática de estudos de neuroimagem

ABSTRACT OBJECTIVE: To perform a systematic review of the literature on the neuroimaging investigation of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) associated with C9ORF72 mutation. METHODS: The search was performed on PubMed and LILACS with the following terms:C9ORF72, MRI, SPECT, PET, ALS, FTD. No filters were added. RESULTS Twenty articles were selected. Most studies found consistent involvement of frontotemporal regions in C9ORF72 carriers, including prefrontal cortex, and also cingulate, subcortical regions, especially the thalami, and posterior regions such as the parietal and occipital lobes. Functional connectivity was also explored and impaired sensorimotor connectivity in striatum and thalami was found in behavioral variant FTDC9ORF72 carriers. Some papers have reported an absence of significant abnormalities on brain imaging. CONCLUSION The inclusion of patients at different stages of the disease, differences in neuroimaging methods across studies, and distinct clinical phenotypes associated with C9ORF72 may account for the heterogeneity of results.

RESUMO OBJETIVO Realizar uma revisão sistemática da literatura sobre os estudos de neuroimagem da demência frontotemporal (DFT) e esclerose lateral amiotrófica (ELA), associadas à mutação C9ORF72. Métodos A pesquisa foi realizada nas bases PubMed e LILACS com os seguintes termos:C9ORF72, MRI, SPECT, PET, ALS, FTD. Nenhum filtro foi utilizado. RESULTADOS Vinte artigos foram incluídos. A maioria dos estudos encontrou, nos portadores da expansão C9ORF72, envolvimento significativo das regiões frontotemporais, incluindo o córtex pré-frontal e também o cíngulo, regiões subcorticais (especialmente o tálamo) e regiões posteriores, como os lobos parietal e occipital. A conectividade funcional também foi investigada e disfunção sensório-motora foi demonstrada no estriado e no tálamo em pacientes com a variante comportamental da DFT associada à expansão C9ORF72. Alguns trabalhos não evidenciaram alterações significativas na neuroimagem. CONCLUSÃO A inclusão de pacientes em diferentes estágios da doença, a variabilidade dos métodos de neuroimagem utilizados nos estudos e os distintos fenótipos de C9ORF72 podem contribuir para a heterogeneidade dos resultados.