Illuminating the Presentation of Hereditary Spastic Paraplegia Type 7 (HSP7)
Emma Snyder1, John Sanderson2, Thomas Bird3, Marie Davis3
1Medical Genetics, 2Internal Medicine, 3Neurology, University of Washington Medical Center
Objective:
To broaden understanding of hereditary spastic paraplegias.
Background:
Hereditary spastic paraplegias (HSPs) are inherited disorders characterized by progressive spastic paraplegia in the lower extremities. Over 80 subtypes have been described; however, clinical recognition of these diseases remains challenging. We present a series of individuals with hereditary spastic paraplegia type 7 (HSP7), highlighting one’s diagnostic odyssey.
Design/Methods:
Descriptive case series.
Results:
An 81-year-old male presented to the neurogenetics clinic for evaluation of progressive gait dysfunction that began in his 30s and progressed to full-time wheelchair dependence at age 77. He had no family members with similar symptoms. He underwent genetic testing for spinocerebellar ataxias type 1, 2, 3, 6, and 7 at age 56 that was unrevealing. Exam findings included saccadic intrusions, mild to moderate dysarthria, and moderate asymmetric lower extremity spasticity. Brain MRI showed cerebellar atrophy since at least age 65, with more recent imaging showing thinning of the corpus callosum. The patient’s wife had noticed some cognitive decline. A multi-gene panel testing for 78 known HSP-associated genes was sent, and revealed homozygosity for SPG7 (c.1529C>T, p.Ala150Val), consistent with diagnosis of autosomal recessive HSP7.
Review of seven additional patients with HSP7 reveals an average delay of 15.34 years between symptom onset and molecular diagnosis. Other common findings included ataxia, cerebellar atrophy, and later-onset of cognitive impairment. Progression to the use of assistive gait devices occurred over decades.
Conclusions:
HSP7 can be challenging to recognize clinically, with several factors contributing to decades of diagnostic delay. It commonly presents with ataxia and a negative family history due to its recessive inheritance, which may focus the workup on sporadic cerebellar etiologies. The high incidence of cognitive impairment in this cohort suggests utility of routine neuropsychological evaluation. Increased awareness of HSP7 and other HSPs will reduce diagnostic delays and help providers serve this rare disease population effectively.
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