[Investigation of Genetic Aetiology in Neurodegenerative Ataxias: Recommendations from the Group of Neurogenetics of Centro Hospitalar São João, Portugal].

Acta Med Port 2017 Jun 30;30(6):502-512. Epub 2017 Jun 30.

Unidade de Neuropediatria. Serviço de Pediatria. Centro Hospitalar São João. Porto. Portugal; Serviço de Genética. Faculdade de Medicina. Universidade do Porto. Porto. Portugal.

In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information) and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

Download full-text PDF

Source
June 2017
5 Reads

Publication Analysis

Top Keywords

neurodegenerative ataxias
20
centro hospitalar
8
group neurogenetics
8
são joão
8
hospitalar são
8
aetiology neurodegenerative
8
neurogenetics centro
8
genetic aetiology
8
ataxias
5
neurodegenerative
5
essential guide
4
history essential
4
loci autosomal
4
guide diagnostic
4
clinical history
4
recessive loci
4
diagnostic workup
4
hold specificity
4
specificity allow
4
well described
4

Similar Publications

[Investigation of Genetic Etiology in Neurodegenerative Dementias: Recommendations from the Centro Hospitalar São João Neurogenetics Group].

Acta Med Port 2016 Oct 31;29(10):675-679. Epub 2016 Oct 31.

Departamento de Neurociências Clínicas e Saúde Mental. Faculdade de Medicina. Universidade do Porto. Porto. Portugal; Serviço de Neurologia. Centro Hospitalar São João. Porto. Portugal.

In the past few years several gene mutations have been identified as causative of the most frequent neurodegenerative dementias (Alzheimer disease and frontotemporal dementia). These advances, along with the complex phenotype-genotype relationships and the costs associated with genetic testing, have often made it difficult for clinicians to decide with regard to a rational plan for the investigation of the genetic etiology of the degenerative dementias. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of Alzheimer disease and frontotemporal dementia in clinical practice, based on international consensus documents (currently containing partly outdated information) and published scientific evidence on this topic. Read More

View Article
October 2016

[Genetic Study of Primary Dystonias: Recommendations from the Centro Hospitalar São João Neurogenetics Group].

Acta Med Port 2017 Apr 28;30(4):340-346. Epub 2017 Apr 28.

Departamento de Neurociências Clínicas e Saúde Mental. Faculdade de Medicina. Universidade do Porto. Porto. Portugal. Serviço de Neurologia. Centro Hospitalar São João. Porto. Portugal.; Serviço de Neurologia, Departamento de Neurociências Clínicas e Saúde Mental, Faculdade de Medicina da Universidade do Porto.

The primary dystonias are a particular group of dystonias of presumed genetic origin, with a wide age of onset and variable progression. The diagnosis is, therefore, a challenge and the issue of the genetic investigation presents frequently in clinical practice. In the past few years several gene mutations have been identified as causative of primary dystonias. Read More

View Article
April 2017

Recent advances in degenerative ataxias.

Authors:
T Klockgether

Curr Opin Neurol 2000 Aug;13(4):451-5

Department of Neurology, University of Bonn, Germany.

Since the discovery of the first mutations that cause hereditary ataxias in the early 1990s, there has been continuous progress in deciphering the molecular pathogenesis of degenerative ataxias. Recent research in Friedreich's ataxia, the most frequent recessive ataxia, has provided further evidence that the clinical phenotype of this disorder is caused by abnormal oxidative phosphorylation due to mitochondrial dysfunction. The dominantly inherited spinocerebellar ataxias (SCAs) are genetically heterogeneous. Read More

View Article
August 2000

EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood.

Eur J Neurol 2014 Apr 13;21(4):552-62. Epub 2014 Jan 13.

Department of Neurology, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.

Background And Objectives: The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer-reviewed evidence-based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. Read More

View Article
April 2014