Turkish Archives of Pediatrics
Original Article

Severe Phenotype in Patients with X-linked Hydrocephalus Caused by a Missense Mutation in L1CAM


Department of Pediatric Genetics, İstanbul University Cerrahpasa, School of Medicine, İstanbul, Turkey


Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, Yale University, Connecticut, USA


Department of Neurology, İstanbul University Cerrahpasa, School of Medicine, İstanbul, Turkey

Turk Arch Pediatr 2022; 57: 521-525
DOI: 10.5152/TurkArchPediatr.2022.22070
Read: 961 Downloads: 310 Published: 01 September 2022

Objective: The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region.

Materials and Methods: Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members.

Results: We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients.

Conclusion: L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely

Cite this article as: Tüysüz B, Ercan-Şençiçek AG, Özer E, Goc N, Yalçınkaya C, Bilguvar K. Severe phenotype in patients with X-linked hydrocephalus caused by a missense mutation in L1CAM. Turk Arch Pediatr. 2022;57(5):521-525.

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