Phenotype description in KIF5C gene hot-spot mutations responsible for malformations of cortical development (MCD).

Abstract

Malformations of cortical development (MCD) represent a large group of brain cortical anomalies characterized by distinctive MRI findings. This 'radiologically-based' classification required re evaluation over time on identified underlying mechanisms (cytogenetic and/or molecular). The understanding of genotype findings (nature of cytogenetic/molecular mutation, cellular pathways consequences, timing, …) draw line of evidence on these distinctive group of conditions whereas sometimes precise and constant recurrent genotype/phenotype correlation may not be present. The clinical diagnosis of MCD is often difficult due to variability and rarity of individual types of malformations. Recent studies have established a relationship between lissencephaly and pathogenic variants in genes involved in the kinesin/tubulin pathways, as the KIF5C gene. Pathogenic variants in the KIF5C gene are a more recently discovered cause of severe developmental delay with epilepsy, characterized by specific malformation of cortical development such as pachygyria. Only seven children have been described to date. We report the natural history of a sixteen years old patient identified carrier of a KIF5C gene mutation who developed infantile epilepsy. We then gather phenotype description and molecular results of all reported patients so far in order to better define this entity.

• Authors: Sophie Duquesne, Marie-Cécile Nassogne, Philippe Clapuyt, Katrien Stouffs, Yves Sznajer
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 63 Issue 9 Pg. 103991 (Sep 2020) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 32562872 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Chemical References

• KIF5C protein, human
• Kinesins

Topics

• Brain (diagnostic imaging)
• Child
• Female
• Humans
• Kinesins (genetics)
• Malformations of Cortical Development (genetics, pathology)
• Mutation
• Phenotype