title: Infantile onset of hereditary spastic paraplegia poorly predicts the genotype.
abstract: Age of symptom onset of hereditary spastic paraplegia varies from infancy to the eighth decade. Infantile onset of hereditary spastic paraplegia without a positive family history may cause difficulties in reaching the correct diagnosis and misdiagnosis as a diplegic form of cerebral palsy is particularly common. Infantile onset of hereditary spastic paraplegia caused by mutations in the spastin gene (SPAST) is very rare and previously was mostly associated with codominant mutations in this gene. We present a kindred with infantile onset of spastic paraplegia in three successive generations caused by confirmed de novo novel mutation 1537G>A (G471D) in SPAST. Several family members were previously diagnosed as having cerebral palsy. Infantile onset of hereditary spastic paraplegia may be caused by mutations in multiple genes, and this phenotype does not reliably predict the genotype. Pediatric neurologists need to be aware of relatively frequent de novo mutations in hereditary spastic paraplegia genes and a possibility that this condition presents in infancy without a positive family history.
authors.affiliation: Department of Neurology; Vanderbilt University, Nashville, TN 37232-8552, USA.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blair
authors.forename: Megan E
authors.initials: ME
authors.lastname: Riddle
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Wells
authors.forename: Brian A
authors.initials: BA
authors.lastname: Breviu
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002547:Cerebral Palsy / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011237:Predictive Value of Tests; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human