A novel L1CAM mutation in a fetus detected by prenatal diagnosis

X-linked hydrocephalus is due to mutations in the L1 neuronal cell adhesion molecule (L1CAM) gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. We report on a familial case diagnosed by prenatal ultrasonographic examination, with cerebellar hypoplasia, agenesis of the corpus callosum, and the bilateral overlapping of the second and third fingers of the hand. Sequencing of the L1CAM gene showed a novel missense mutation in exon 14: transition of a guanine to cytosine at position 1777 (c.1777G > C), which led to an amino acid change of alanine to proline at position 593 (Ala593Pro) in the sixth immunoglobulin domain of the L1 protein. The L1CAM mutation testing should be considered in fetuses with ultrasonographic signs of hydrocephalus and a positive family history compatible with X-linked inheritance. We agree with previous reports that suggest also considering limb abnormalities other than adducted thumbs in addition to classical neurological disgenesis, as characteristic for L1-disease