Kennedy disease (AR expansions)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a prevalence of 5.4/100,000 (Chiò et al., 2013). Even though most cases are of sporadic presentation, previous family history exists in 10% of patients. Pathogenic variants in the C9orf72, SOD1, TARDBP, and FUS genes explain almost two thirds of the familial forms (25%, 20%, 5%, and 5% respectively). In the C9orf72 gene, a single genetic alteration associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia has been detected, consisting of a (GGGGCC)n repeat expansion not detectable by next generation sequencing.

Primary lateral sclerosis (PLS) is characterized by isolated involvement of upper motor neurons, which distinguishes it from amyotrophic lateral sclerosis, where lower motor neurons are also compromised. The diagnosis of PLS is made by excluding disease causes such as spastic paraplegia, multiple sclerosis, metabolic disease, or myelopathy