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.

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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.

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

 

Abstract

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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