Rare form of SPG4 HSP misdiagnosed

Posted - February 2018 in Research Highlights

Early-onset symptoms “misleading”


In two unrelated girls with no family history of HSP and with early-onset spasticity, SPG4 HSP would not normally be amongst the suspects.


However, genetic diagnosis of the exact same mutation was found in both these cases, following misdiagnosis as cerebral palsy in one child and tethered cord in the other.


More than 250 HSP-causing mutations in the SPAST gene (SPG4 type HSP) have now been identified.



Hereditary spastic paraplegia is a phenotypically and genetically heterogeneous group of neurodegenerative disorders characterized by lower extremity weakness and spasticity.


Spastic paraplegia 4 (SPG4), caused by heterozygous mutations in the gene SPAST, typically causes a late-onset, uncomplicated form of hereditary spastic paraplegia in affected individuals. Additional clinical features in SPG4 have been reported on occasion, but no genotype-phenotype correlation has been established.


Through targeted clinical testing, we identified 2 unrelated female patients with the same de novo p.Arg499His mutation in SPAST. Both patients presented with early-onset spasticity resulting in delayed motor milestones, which led to a diagnosis of cerebral palsy in one child and tethered cord in the other.


Review of the literature identified several patients with mutations at amino acid 499 and early-onset symptoms associated with a risk of cognitive impairment. Early and accurate diagnosis of children with early-onset spasticity is important for informed prognosis and genetic counselling.


SOURCE: J Child Neurol. 2018 Jan 1:883073818756680. doi: 10.1177/0883073818756680. [Epub ahead of print] PMID: 29421991


Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in SPAST.


Gillespie MK1, Humphreys P1,2, McMillan HJ1,2, Boycott KM1,3.

1 Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.

2 Division of Neurology, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.

3 Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada.

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