Abstract Details

Key genetic testing parameters assessed included clinical utility, testing model and modality, genetic counseling, reimbursement, turn-around-time, and test quality through various public private resources and nearly 40 labs in the US. Frequency of SOD1 and C9ORF72 among cases reported as familial and sporadic were estimated and compared to published rates from large population-based studies or ALS case series.

Classification of ALS as familial or sporadic based on presence of family history has some inherent limitations such as difficulty in complete and accurate assessment due to imperfect knowledge or recall, lack of a standardized definition of familial ALS (e.g. among 1^st degree only vs. extended family, family history of ALS only vs. inclusion of FTD/dementia), and shared environmental risk factors.  Clinical care guidelines contain limited guidance on genetic testing and there is no standard single test for genetic ALS. Reimbursement is limited to familial cases and genetic testing is typically associated with long turn-around times. Estimated proportion of cases classified in the literature as seemingly sporadic ranged from 40% to 60% among SOD1 cases and 57% to 74% among C9orf72 cases. These estimates are consistent with results from studies with systematic testing of all ALS cases regardless of familial status.

The high proportion of seemingly sporadic cases among SOD1 and C9ORF72 ALS suggests many ALS cases of monogenetic etiology are not being identified. Genetically targeted therapies will increase the need for genetic testing in the future, which suggests a need to move beyond research genotyping to routine clinical genetic testing of all patients with ALS.