Abnormal course of the corticospinal tracts in KIF5C-related encephalopathy

Alessandro Naim; Andrea Accogli; Elisabetta Amadori; Gianluca D'Onofrio; Francesca Madia; Domenico Tortora; Federico Zara; Pasquale Striano; Vincenzo Salpietro; Mariasavina Severino

doi:10.1016/j.ejmg.2022.104622

Abnormal course of the corticospinal tracts in KIF5C-related encephalopathy

Eur J Med Genet. 2022 Nov;65(11):104622. doi: 10.1016/j.ejmg.2022.104622. Epub 2022 Sep 16.

Affiliations

¹ Pediatric Neurology and Muscular Diseases Unit, IRCCS "G. Gaslini" Institute, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Unit of Medical Genetics, IRCCS Giannina Gaslini Institute, Genova, Italy.
² Division of Medical Genetics, Department of Specialized Medicine, Montreal Children's Hospital, McGill University Health Centre (MUHC), Montreal, QC, H4A 3J1, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada.
³ UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, University of Genoa, 16147, Genoa, Italy.
⁴ Neuroradiology Unit IRCCS, Istituto Giannina Gaslini, Genoa, Italy.
⁵ Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Unit of Medical Genetics, IRCCS Giannina Gaslini Institute, Genova, Italy; UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, University of Genoa, 16147, Genoa, Italy.
⁶ Pediatric Neurology and Muscular Diseases Unit, IRCCS "G. Gaslini" Institute, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Unit of Medical Genetics, IRCCS Giannina Gaslini Institute, Genova, Italy. Electronic address: v.salpietro@ucl.ac.uk.

PMID: 36122673
DOI: 10.1016/j.ejmg.2022.104622

Abstract

KIF5C encodes a protein belonging to the kinesin family and involved in cellular transport. Variants in KIF5C were first associated a decade ago with microcephaly and malformations of cortical development, with a phenotypic spectrum ranging from polymicrogyria to pachygyria. Currently, eight patients have been reported so far. Here we describe a new paediatric patient carrying the recurrent p.(Glu237Lys) KIF5C variant associated with a distinctive neuroradiological pattern of abnormal posterior course of the corticospinal tract at the level of the pons with a thickened anterior component of the transverse pontine fibers. This finding is likely related to altered axonal guidance and requires further evidence in other patients with KIF5C-related disorder.

Keywords: Diffusion tensor imaging (up to 6); Epilepsy; KIF5C; Kinesin; Malformations of cortical development.

MeSH terms

Brain Diseases*
Child
Humans
Kinesins / genetics
Lissencephaly*
Pyramidal Tracts / diagnostic imaging
White Matter*

Substances

KIF5C protein, human
Kinesins