Hydrocephalus generally refers to a disorder of cerebrospinal fluid physiology resulting
in abnormal expansion of the cerebral ventricles, typically associated with increased
intracranial pressure. The prevalence of infant hydrocephalus is ∼1:10,000. In the
large majority of cases, the pathophysiological defect is unknown. Recently, some
genetic causes of inherited congenital hydrocephalus have been identified, whereas
most are only reported in a small number of families.
We performed whole exome sequencing in a cohort of 14 individuals suffering from congenital
hydrocephalus. In three individuals, we identified monogenetic variants for hydrocephalus
in already known hydrocephalus-associated genes (L1CAM, MPDZ; POMGNT2). Interestingly
in one individual who was also suffering from respiratory symptoms, we identified
homozygous loss-of-function mutations in CCDC40. Mutations in CCDC40 cause motility
defects in motile cilia. This disease is known as primary ciliary dyskinesia. In one
patient, a numerical chromosomal aberration was detected.
Through whole exome sequencing, we were able to detect the genetic reason for hydrocephalus
in 36% of cases. In our small cohort, at least one-third is caused by genetic reasons.
Since additionally we were able to detect variants in two patients in a candidate
gene, we assume that monogenetic reasons are a major cause of congenital hydrocephalus.
