Genetic factors in the early diagnosis of ALS

The frequency of familial amyotrophic lateral sclerosis (ALS) is usually reported as 5-10% of all ALS cases. This figure is probably an underestimate, primarily due to inadequate recording of family history in the patients' charts, and to the not infrequent occurrence of reduced disease penetrance in pedigrees with familial ALS. The true familial ALS frequency may be at least double this. Familial ALS is heterogenetic. The only known ALS-causing gene is the CuZn-superoxide dismutase gene (CuZn-SOD). Mutations in this gene account for a fifth of all familial ALS cases and a few percent of apparent sporadic ALS cases. Genetic testing for CuZn-SOD mutations can help confirm a diagnosis of ALS, especially in cases with atypical features that have been reported in some cases with CuZn-SOD mutations. Genetic testing should only be performed after thorough clinical examination and in cases with a proven or uncertain family history of ALS. It is not warranted in cases with no proven family history for three generations, unless the patient shows the characteristic phenotype associated with recessive inheritance of the D90A CuZn-SOD mutation.