CHL1 Deletion is Associated with Cognitive and Language Disabilities - Case Report and Review of Literature

Background: There is a small, but growing number of reports of pediatric patients with terminal deletions at 3p26.3 involving only the cell adhesion molecule L1-like (CHL1) gene that has been found to have language delays and intellectual disability. Here we report a one month of age patient who developed seizures and tone abnormalities, with persistent and prominent gross and fine motor delays. The patient has microcephaly and deficits in language and cognitive delays, similar to what has been seen in previous case reports.

Methods: Chromosome and microarray comparative genomic hybridization (aCGH) analysis was performed to identify clinically significant copy number variants (CNVs). In addition, Fluorescent in-situ hybridization (FISH) was performed to confirm the aCGH findings.

Results: Chromosome analysis revealed an apparently normal (46,XX) female karyotype. Microarray CGH analysis revealed a 639 kb loss at 3p26.3 from 62199 to 701052 base pairs encompassing the whole CHL1 gene that was confirmed by FISH. Parental follow-up revealed the deletion as maternal in origin.

Conclusion: This case report adds to the limited body of literature that exists on this terminal deletion at 3p26.3 that involves CHL1 gene, and supports prior proposals of an emerging CHL1 microdeletion syndrome that results in language and cognitive delays. Further studies are needed to understand the degree of phenotypic heterogeneity associated with CHL1 gene deletion and whether the size of the deletion or presence of additional copy number variants (CNVs) which were seen in other case reports help predict the expected phenotype for a patient.