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

• Published in: Journal of the peripheral nervous system Vol. 25; no. 2; pp. 117 - 124
• Main Authors: Nemani, Tarishi, Steel, Dora, Kaliakatsos, Marios, DeVile, Catherine, Ververi, Athina, Scott, Richard, Getov, Spas, Sudhakar, Sniya, Male, Alison, Mankad, Kshitij, Muntoni, Francesco, Reilly, Mary M, Kurian, Manju A, Carr, Lucinda, Munot, Pinki
• Format: Journal Article
• Language: English
• Published: Malden, USA Wiley Periodicals, Inc 01.06.2020; Wiley Subscription Services, Inc
• Subjects: Atrophy; Autonomic nervous system; Children; Dysautonomia; Dystonia; Epilepsy; hereditary spastic paraparesis; KIF1A; Magnetic resonance imaging; Movement disorders; Mutation; Nervous system; Neurological diseases; neuropathy; Optic atrophy; Optic neuropathy; Phenotypes; Polyneuropathy; Sensorimotor system; Spasticity; Substantia alba; neuropathy; hereditary spastic paraparesis; KIF1A; dysautonomia; dystonia
• ISSN: 1085-9489; 1529-8027
• DOI: 10.1111/jns.12368

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.