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. 2020 Jun;25(2):117-124.
doi: 10.1111/jns.12368. Epub 2020 Mar 6.

KIF1A-related disorders in children: A wide spectrum of central and peripheral nervous system involvement

Tarishi Nemani  1 , Dora Steel  1   2 , Marios Kaliakatsos  1 , Catherine DeVile  1 , Athina Ververi  3 , Richard Scott  3 , Spas Getov  4 , Sniya Sudhakar  5 , Alison Male  3 , Kshitij Mankad  5 ; Genomics England Research Consortium  6 ; Francesco Muntoni  1   2 , Mary M Reilly  7 , Manju A Kurian  1   2 , Lucinda Carr  1 , Pinki Munot  1
Affiliations

KIF1A-related disorders in children: A wide spectrum of central and peripheral nervous system involvement

Tarishi Nemani et al. J Peripher Nerv Syst. 2020 Jun.

Abstract

KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological, and radiological features which may occur in childhood-onset KRD. We report on all the children and young people seen at a single large tertiary centre. Data were collected through a retrospective case-notes review. Twelve individuals from 10 families were identified. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children. This case series demonstrates that KRD comprise a range of neurological disorders, with both the milder and the more severe forms combining central and peripheral (including autonomic) nervous system deficits.

Keywords: KIF1A; dysautonomia; dystonia; hereditary spastic paraparesis; neuropathy.

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References

REFERENCES

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