Clinical and genetic features of L1 syndrome patients: Definition of two novel mutations

•We present two L1 syndrome cases with novel mutations in the L1CAM gene.•In patients with hydrocephalus and adducted thumbs L1 syndrome should be considered.•In patients with severe phenotype microcephaly, as well as macrocephaly, could be seen. L1 syndrome is a rare X linked recessive disorder caused bygene mutations in the L1 cell adhesion molecule (L1CAM), and characterized by hydrocephalus, intellectual disability, adducted thumbs and spasticity of the legs. The gene encodes a protein which plays an important role in neuronal development. Two unrelated L1 syndrome cases, with global developmental delay and hydrocephalus, were referred to pediatric genetics subdivision for genetic counseling. Bilateral adducted thumbs and spasticity in the lower extremities were also observed in both patients. Molecular analysis revealed two novel hemizygous mutations in the patients: a deletion mutation (c.749delG; p.Ser250Thrfs*51) and a splicing mutation (c.3166+1G>A). To conclude; in male patients with intellectual disability and hydrocephalus, where adducted thumbs are present, L1 syndrome should be considered.