X-linked hydrocephalus: Another family with a novel mutation in the L1CAM-gene

We report on a family with two male siblings (age 2 2/12 years and 9 month) suffering from connatal hydrocephalus.

Hydrocephalus was diagnosed at gestational age of 21 weeks in both pregnancies. The first patient was delivered at 35 weeks by cesarean section because of progressive ventricular dilatation, which was shunted within the first week. Further symptoms include adducted thumbs and severe mental and motor retardation with spastic cerebral palsy after initial muscular hypotonia. MRI revealed hypoplasia of corpus callosum, thickened interthalamic junction, reduced white matter and aqueductal agenesis. His brother was delivered by cesarean section at 37 weeks for the same reason and shunted the next day. Additional symptoms include adducted thumbs and delayed motor development.

Genetics: X-linked hydrocephalus was suspected. Screening of the L1CAM-gene on chromosome Xq28 showed a novel mutation at position c.3004G>T on the X-chromosome in both boys and heterocygous in the clinically unaffected mother.

Discussion: The L1CAM-gene codes for a neural cell adhesion molecule. The transmembrane glycoprotein belongs to the Ig-superfamily and plays an important role in neuronal migration and neurite outgrowth. Mutations can cause a spectrum of diseases: X-linked hydrocephalus due to aqueductal stenosis, MASA-syndrome (mental retardation, aphasia, shuffling gait, adducted thumbs), X-linked spastic paraplegia. These „syndromes“ represent a spectrum of symptoms due to L1CAM-Mutations and can vary even within a pedigree. As in our family, most mutations reported are point mutations leading to missense, nonsense or splice site alterations of the gene.