Genetics of primary lateral sclerosis

Abstract

With the exception of rare, juvenile-onset, autosomal recessive cases, primary lateral sclerosis (PLS) has long been considered an exclusively sporadic motor neuron disease. However, the identification of PLS cases within pedigrees with familial amyotrophic lateral sclerosis (ALS), together with the clinical and neuropathological overlap with other neurodegenerative disease with strong genetic component such as ALS and hereditary spastic paraparesis (HSP), suggest the existence of a genetic component in PLS as well. Here we will review the genetics of juvenile PLS-like syndromes and the contribution of mutations in ALS and HSP-associated genes to PLS pathogenesis.

Keywords:

• Genetics
• PLS
• neuropathology

Declaration of interest

VS is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology; received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, and Italfarmaco; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and E-Rare Joint Transnational Call.

PC received compensation for consulting services and/or speaking activities from Biogen and Cytokinetics.

GR is on the Board of ALS Pharma, but without shares or options in the company.

MBH, TS and NT report no disclosures.