Primary lateral sclerosis and amyotrophic lateral sclerosis (ALS) are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria established. PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons.
Lerman-Sagie et al. (1996) described a Kuwaiti family with Juvenile ALS. The parents were healthy and consanguineous, and had three affected sons. The patients developed progressive paralysis of the lower extremities in infancy, followed by involvement of the upper extremities and bulbar muscles. Hadano et al. (2001) searched for DNA variations in the ALS2CR6 gene in this family and found a 2-bp deletion (c.1548delAG) in homozygous state in all patients. Both parents were heterozygous for this mutation, as was another brother. The Online Mendelian Inheritance in Man Database corrected the nomenclature of the mutation as c.1425delAG. Shaw (2001) classified this family as having primary lateral sclerosis because of the lack of evidence of denervation.
In three affected members of a consanguineous Saudi Arabian family with juvenile primary lateral sclerosis, Yang et al. (2001) identified a homozygous 2-bp deletion (c.1867delCT) in exon 9 of the ALS2 gene.