Amyotrophic lateral sclerosis (ALS), a subtype of Motor Neuron Disease (MND), is a neurodegenerative disorder affecting motor neurones. The incidence has been reported to be 0.6-2.6 per 100,000. 90% of ALS cases occur sporadically and it is not known if sporadic ALS is polygenic or multi-factorial. Familial inheritance is estimated to occur in 10% of cases. Ireland represents an ideal location for performing a genetic epidemiology study of ALS owing to the genetically homogeneous nature of the Irish population and the existence of a detailed register of all cases of ALS diagnosed since 1995.

The main aim of the family aggregation study is to estimate the relative contribution of genetics to ALS and to clarify the mode of genetic transmission of ALS using data from a population-based unbiased sample of Irish ALS patients. An in-depth review of familial cases over two decades will also be made in order to ascertain the true rate of familial ALS as well as phenotypic variation among the Irish cohort.

While the El Escorial criterion classifies definite ALS purely as a neurodegenerative disorder of the motor system there is a growing body of evidence that associates a certain phenotype of ALS with cognitive impairment. Even the earliest investigation into familial ALS by Kurland and Mulder in the 1950’s demonstrated other neurodegenerative conditions among relatives of people with ALS. Assessment of segregation analysis and familial aggregation for other neurodegenerative disorders in relatives will be made. If it is proven that there is a higher incidence it could be proposed that these neurodegenerative disorders share a genetic susceptibility locus, and further focused genetic analysis will be carried out.

Detailed family histories will be collected from consenting patients via questionnaire format and then verified by a researcher. Controls will be recruited from age and geographically matched individuals.

To summarise, a family history study will be carried out primarily to determine a model of genetic transmission of ALS in the Irish population, assess familial aggregation and the pattern of familial recurrence risk for ALS. The information gathered will be of use to genetic counsellors when speaking to families.

The secondary aim will be to assess the relative risk of neurodegenerative diseases among relatives of ALS patients. This type of study is essential before laboratory studies are carried out to look for genetic loci.