L1 Syndrome-Associated Phenotypes and a Novel L1CAM Variant: A Clinical Report

Abstract

L1 syndrome is a group of X-linked diseases caused by pathogenic variants in the human L1 cell adhesion molecule gene (L1CAM; OMIM 308840). The L1CAM gene is expressed primarily in the nervous system, where it plays important roles in neuronal development, including the guidance of neurite outgrowth, neuronal cell migration, axon bundling, synaptogenesis, myelination, neuronal cell survival, and long-term potentiation. L1 syndrome comprises a group of overlapping phenotypes including partial agenesis of corpus callosum, congenital X-linked hydrocephalus, and mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome. Molecular analysis was performed in four patients with congenital hydrocephalus (CH) and adducted thumbs. Three pathogenic variants were identified in the L1CAM gene, novel c.539dupA (p.Gln181Alafs*46) common to the two siblings, c.791G > A (p.Cys264Tyr) and c.1453C > T (p.Arg485*) variants. A correlation between genotype and phenotype has been reported in L1-related disorders. Two families with intrafamilial variability are presented and a novel pathogenic variant in the L1CAM gene has been reported. L1 syndrome should be considered primarily in patients with CH and adducted thumbs.

Keywords

L1 syndrome - L1CAM gene - congenital hydrocephalus - adducted thumbs

Ethical Approval

This study was approved by the Erciyes University Clinical Research Ethics Committee (Approval Number: 2022/443).

Informed Consent

Informed consent was obtained from the parents of the L1 syndrome patient and also the authors affirm that human research participants provided informed consent for the publication of the images in [Fig. 1].

Authors' Contributions

All authors contributed significantly to the design of the study, obtaining the data, analyzing and interpreting the data, drafting the manuscript, and critically reviewing it for important intellectual content, final approval the version.

Publication History

Received: 30 October 2023

Accepted: 27 March 2024

Article published online:
25 April 2024

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