From the Guidelines
Congenital hydrocephalus is primarily caused by neural tube defects, such as spina bifida and myelomeningocele, as well as other factors like aqueductal stenosis, genetic disorders, and intrauterine infections, which disrupt the normal flow or absorption of cerebrospinal fluid (CSF) during fetal development. The most common causes of congenital hydrocephalus can be categorized into several groups, including:
- Neural tube defects, such as spina bifida and myelomeningocele, which affect approximately 1 in 1,000 births 1
- Aqueductal stenosis, a narrowing of the cerebral aqueduct connecting the third and fourth ventricles 1
- Genetic disorders like X-linked hydrocephalus (caused by mutations in the L1CAM gene) and Dandy-Walker malformation, which affects the cerebellum and fourth ventricle 1
- Intrauterine infections during pregnancy, particularly TORCH infections (Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, and Herpes simplex), which can damage the developing brain and cause hydrocephalus 1
- Brain malformations such as Chiari malformations and arachnoid cysts, which can obstruct CSF flow 1 The underlying mechanism involves either overproduction of CSF, obstruction of CSF flow pathways, or impaired absorption of CSF, leading to ventricle enlargement and increased intracranial pressure that can damage developing brain tissue if not treated promptly 1.
According to a systematic review and meta-analysis published in The Lancet Global Health in 2022 1, the categorization of aetiologies of paediatric hydrocephalus includes post-infectious hydrocephalus, non-postinfectious hydrocephalus, spinal dysraphism, and unclear causes. This study highlights the importance of understanding the aetiology of congenital hydrocephalus in order to provide appropriate treatment and care.
In terms of morbidity, mortality, and quality of life, it is essential to promptly diagnose and treat congenital hydrocephalus to prevent severe neurological deficiencies and improve outcomes 1. Therefore, it is crucial to consider a comprehensive approach to diagnosing and managing congenital hydrocephalus, taking into account the various causes and underlying mechanisms.
From the Research
Causes of Congenital Hydrocephalus
The causes of congenital hydrocephalus are diverse and can be attributed to various factors, including:
- Congenital malformations of the central nervous system 2
- Infections, such as congenital toxoplasmosis 3
- Haemorrhage, trauma, teratogens, and tumours 2
- Genetic mutations, with X-linked hydrocephalus comprising approximately 5% of all cases 2
Genetic Basis
The genetic basis of hydrocephalus is complex and involves multiple genes and pathways 4. Studies have identified several genes that contribute to the development of congenital hydrocephalus, including:
- L1CAM and AP1S2, which are associated with X-linked hydrocephalus 2, 5
- CCDC88C and MPDZ, which are associated with autosomal recessive hydrocephalus 5
- EML1, WDR81, and other genes that have been identified as novel causes of congenital hydrocephalus 5
Disease-Specific Factors
Research suggests that disease-specific factors, such as proximity to telomeres and high adenine and thymine (A + T) content, may contribute to the genetic mutations that cause congenital hydrocephalus 6. These factors may be used to prioritize putative genes found in preclinical models and identify the genetic basis of congenital hydrocephalus.
Clinical Implications
Understanding the causes and genetic basis of congenital hydrocephalus is essential for developing effective diagnostic and therapeutic strategies. Early diagnosis and treatment, such as ventriculoperitoneal shunt placement, can improve clinical outcomes in patients with hydrocephalus secondary to congenital toxoplasmosis 3. However, the prognosis for patients with congenital hydrocephalus depends on the underlying cause and associated malformations, highlighting the need for further research into the genetic and molecular mechanisms of this condition 2, 4.