[Atypical spastic paraplegia type 4 due to p.Arg499His mutation in SPAST gene]

A case of spastic paraplegia type 4 (SPG4) due to SPAST p.Arg499His mutation de novo in a child, aged 2 years 8 months, is presented. The differences of this first Russian case with the mutation and of a number of reported cases from typical SPG4 are very early onset, severe disabling spasticity and additional signs, cognitive disturbances in particular; SPAST mutations de novo are also infrequent. Specific patterns point to the relationship between genotype and phenotype. Methods of exome sequencing are particularly informative in atypical cases difficult for clinical diagnostics.