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.

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

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.

Received: 30 October 2023

Accepted: 27 March 2024

Article published online:
25 April 2024

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