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RARE DISEASE

Hydrocephalus with stenosis of the aqueduct of Sylvius

Synonyms: Bickers-Adams syndrome, HSAS, X-linked HSAS, X-linked acqueductal stenosis, X-linked hydrocephalus, X-linked hydrocephalus with stenosis of aqueduct of Sylvius

Drug discovery

papers

On emerging therapies

Overview

Hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) is a form of non-communicating hydrocephalus caused by narrowing or blockage of the cerebral aqueduct, leading to impaired CSF flow. It manifests with symptoms such as headache, nausea, cognitive impairment, gait disturbances, and upward gaze palsy. Diagnosed via MRI showing triventricular enlargement with a normal fourth ventricle, it is managed surgically through endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting [1][3][6][11][16].

Population

Congenital cases account for 70% of AS, often presenting in infancy or childhood (peak <1 year), with X-linked hydrocephalus (L1 syndrome) linked to genetic mutations [1][9][16].
Bimodal age distribution: Second peak in adults (40–60 years), with male predominance (72% of late-onset cases) [6][11].

Burden

Congenital HSAS prevalence: 0.1–0.3% of live births, contributing to ~10% of adult hydrocephalus cases [9][16].
Untreated cases risk irreversible brain damage, coma, or death; treated patients may experience residual deficits (cognitive delay, motor dysfunction) [1][6][7].
High healthcare costs from lifelong shunt revisions and neurodevelopmental support, particularly in pediatric populations [6][11].

Therapies

Endoscopic third ventriculostomy (ETV): First-line treatment with 60–80% success in adults but lower efficacy in infants [3][11][16].
Shunt placement: Ventriculoperitoneal shunts are used for failed ETV or complex cases, though prone to lifelong complications (e.g., infections, blockages) [8][11][16].
Adjuvant care: Regular neuroimaging, cognitive rehabilitation, and monitoring for late decompensation [6][12].

Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases

Research Papers

24 drug discovery papers about Hydrocephalus with stenosis of the aqueduct of Sylvius. Recent publications:

categories:

Small molecules

gene therapies

2024-08-13 | Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

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gene therapies

2024-08-13 | Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

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Drug Discovery Landscape

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Hydrocephalus with stenosis of the aqueduct of Sylvius

Hydrocephalus with stenosis of the aqueduct of Sylvius

Hydrocephalus with stenosis of the aqueduct of Sylvius

Overview

Population

Burden

Therapies

Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases

Research Papers

gene therapies

2024-08-13 | Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

gene therapies

2024-08-13 | Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms.

Drug Discovery Landscape

Updated: Nov 10, 2026