The ALS Gene Curation Expert panel will evaluate the evidence for genes that have been linked to the phenotype of amyotrophic lateral sclerosis (ALS).  This will include the ALS-spectrum phenotypes of progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), and progressive bulbar palsy. 

Because both upper and lower motor neuron degeneration can occur in other genetic neurodegenerative disease, the panel will largely exclude genes where an occasional patient meets criteria for ALS in addition to their more typical features (e.g. DJ1 in early onset parkinson’s disease; NOP36 in spinocerebellar ataxia where bulbar atrophy is observed; several of the complicated hereditary spastic paraplegia genes).  However, the panel will evaluate genes typically associated with a non-ALS disease under two circumstances:  if there are multiple reports of patients with ALS that lack features of the typical disease (e.g. VCP, ATXN2, or BSCL2) or if the typical neurodegenerative disease associated with the gene is frontotemporal dementia (e.g. CHMP2B, GRN).  The latter exception is due to the very tight link between ALS and FTD.

We also plan to include a narrow set of clinically distinct degenerative motor neuron diseases that each has very little genetic heterogeneity at this point: spinobulbar muscular atrophy/Kennedy’s disease; juvenile ALS; juvenile PLS, Fazio-Londe disease and Brown-Vialetto-Van Laere syndrome. 

The ALS GCEP will not include the spinal muscular atrophies, distal hereditary motor neuropathies, distal SMA, distal CMT, fronto-temporal dementia, multisystemic proteinopathies, or Troyer’s syndrome.