Hydrocephalus is a neurological condition where cerebrospinal fluid (CSF) accumulates within the brain’s ventricles. This excess fluid causes enlarged ventricles and increased pressure on brain tissues.
What is Hydrocephalus?
Cerebrospinal fluid (CSF) is a clear fluid that surrounds the brain and spinal cord, delivering nutrients and removing waste. Normally, CSF flows through interconnected brain cavities called ventricles and is reabsorbed into the bloodstream. Hydrocephalus results from an imbalance in this system, due to overproduction, impaired absorption, or a blockage in its flow.
The condition is classified into communicating and non-communicating types. Communicating hydrocephalus occurs when CSF flow is blocked after exiting the ventricles, but fluid can still move between them. Non-communicating, or obstructive, hydrocephalus involves a blockage within the narrow passages connecting the ventricles, preventing CSF circulation.
The Role of Genetics in Hydrocephalus
Hydrocephalus can have a genetic basis, though many cases are not inherited. Genetic factors contribute to up to 50% of congenital hydrocephalus cases, which are present at birth. These genetic forms often involve mutations in genes affecting brain development, CSF pathways, or ventricle lining cells. Genetic causes can manifest as part of a broader genetic syndrome or as isolated hydrocephalus. Identifying the specific genetic cause can provide insights into the condition’s progression and potential implications.
Inherited Forms and Syndromes
Specific genetic conditions can cause hydrocephalus, with varying inheritance patterns. X-linked hydrocephalus, caused by L1CAM gene mutations on the X chromosome, is a prominent example. This form leads to narrowing of the aqueduct of Sylvius and severe ventricular enlargement, occurring almost exclusively in males. Females can be carriers with a low chance of symptoms.
Other genetic syndromes, like Dandy-Walker and certain Chiari malformations, also feature hydrocephalus due to structural brain abnormalities disrupting CSF flow. Autosomal dominant and recessive inheritance patterns also contribute. For instance, mutations in genes like MPDZ and CCDC88C, involved in cell polarity and migration, have been linked to non-syndromic autosomal recessive hydrocephalus. Over 100 causative genes have been identified in syndromic hydrocephalus, highlighting its complex genetic landscape.
Other Causes of Hydrocephalus
Beyond genetic factors, hydrocephalus can arise from non-inherited causes, categorized as congenital (present at birth but not genetic) or acquired (developing after birth). Congenital non-genetic causes include infections during pregnancy, such as rubella, which inflame fetal brain tissues. Complications of premature birth, like intraventricular hemorrhage, can also lead to hydrocephalus in newborns.
Acquired hydrocephalus can develop at any age from various events. Common causes include head injuries, where blood from ruptured vessels can block CSF pathways or scar membranes, restricting fluid flow. Brain tumors can obstruct CSF circulation by compressing ventricles or overproducing fluid. Infections like meningitis, which inflame brain and spinal cord membranes, can also lead to acquired hydrocephalus by scarring CSF pathways.
Genetic Considerations for Families
For families affected by hydrocephalus, genetic counseling is important for understanding potential genetic origins. Genetic counselors assess the likelihood of a genetic cause, explain inheritance patterns, and discuss implications for family members. This process involves evaluating family history and recommending genetic testing when appropriate.
Genetic testing, including targeted gene panels or exome sequencing, can identify specific gene mutations. This information is valuable for determining recurrence risk for future pregnancies. While recurrence risk for non-X-linked congenital hydrocephalus is low (less than 1% to 4%), identifying a genetic cause provides clarity and informs family planning.