Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam, 1945-1972. II. Familial and genetic studies.

The extraordinarily high rate of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the Chamorro linguistic group on Guam suggested a genetic etiology for these diseases. Results of three studies are described. Two involved comparisons of the rates of disease in relatives and spouses of index patients and controls. In the third we examined offspring of doubly affected parents, 10 spouse pairs with ALS, 3 spouse pairs with PD and 13 spouse pairs in which 1 spouse had ALS and the other PD. Within the limitations of numbers and age of offspring, we found a tendency among siblings and offspring of ALS cases to have a higher risk than control relatives. Numbers were small and in no instance were significant differences encountered. Spouses of patients had at least as high risk of developing ALS or PD as any of the groups of blood relatives. A slightly higher age-specific rate of ALS and PD occurred in the offspring of doubly affected parents. The only group large enough for present analysis are 60 offspring of doubly affected ALS parents over the age of 20. Thus far only 3 have developed ALS. Within our entire patient population of 350 ALS cases and 219 PD cases there were 12 instances in which one parent of the patient was not Chamorro. In addition there is a consistent two- to threefold excess of affected males which could not be accounted for by competitive risks of death from other causes among females. While a familial tendency does exist these findings and observations are not compatible with any simple Mendelian form of inheritance. It is possible that genetic influences affect the occurrence of these diseases but our studies suggest that environmental factors play at least as important a role.