FV 1177. Genetic Causes of Congenital Hydrocephalus

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.

Die Autoren geben an, dass kein Interessenkonflikt besteht.