What are the other Names for this Condition? (Also known as/Synonyms)

• X-Linked Aqueductal Stenosis (XLAS)
• X-Linked Hydrocephalus (HYCX)
• X-Linked Hydrocephalus with Congenital Idiopathic Intestinal Pseudo-Obstruction

What is Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius? (Definition/Background Information)

• Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius (HSAS) is a form of L1 syndrome, which is an inherited disorder that primarily affects the nervous system
• Males with HSAS are typically born with severe hydrocephalus and adducted thumbs (bent towards the palm)
• A diagnosis of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is typically suspected based on the presence of characteristic signs and symptoms on physical examination and/or brain imaging (i.e. CT scan, MRI scan). Identification of a change (mutation) in the L1CAM gene can be used to confirm the diagnosis
• Other sign and symptoms of the condition include severe intellectual disability and spasticity. HSAS, like all forms of L1 syndrome, is caused by changes (mutations) in the L1CAM gene and is inherited in an X-linked recessive manner
• Treatment is based on the signs and symptoms present in each person

(Source: Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius? (Age and Sex Distribution)

• Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is a rare congenital disorder. The presentation of symptoms may occur at birth
• Predominantly males are affected, since it is an X-linked condition
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius can be inherited
• Currently, no other risk factors have been clearly identified for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius? (Etiology)

Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is inherited in an X-linked recessive manner.

• A condition is X-linked if the responsible gene is located on the X chromosome. The X chromosome is one of the two sex chromosomes (the other sex chromosome is the Y chromosome)
• Females have two X chromosomes in each cell and males have an X chromosome and a Y chromosome in each cell.
• Although females have two X chromosomes, one of the X chromosomes in each cell is "turned off" and all of the genes on that chromosome are inactivated. Females who have a change (mutation) in a gene on one of their X chromosomes are called carriers of the related condition
• Carrier females usually do not have symptoms of the condition because the X chromosome with the mutated gene is often turned off and they have another X chromosome with a working copy of the gene. Sometimes, the X chromosome with the working copy of the gene is turned off, which may cause symptoms of the condition
• However, females with symptoms are usually much more mildly affected than males.
• A male has only one X chromosome, so if he inherits a mutation on the X chromosome, he will have signs and symptoms (be affected).
• Males with an X-linked recessive condition always pass the mutated gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome to male offspring.
• Female carriers of an X-linked recessive condition have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have an affected son, and a 25% chance to have an unaffected son
• This also means that each daughter of a carrier mother has a 50% chance of being a carrier, and each son has a 50% chance of having the condition

(Source: Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius?

The signs and symptoms of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius may include:

• Corticospinal tract hypoplasia
• Intellectual disability
• Macrocephaly
• Spastic paraplegia

Very frequently present symptoms in 80-99% of the cases:

• Aqueductal stenosis
• Hemiplegia/hemiparesis
• Hydrocephalus
• Increased intracranial pressure
• Intellectual disability, severe
• Spasticity

Frequently present symptoms in 30-79% of the cases: Adducted thumb

Occasionally present symptoms in 5-29% of the cases:

• Absent septum pellucidum
• Agenesis of corpus callosum
• Coarse facial features
• Holoprosencephaly
• Joint stiffness
• Nystagmus
• Seizures
• Strabismus

Males with Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius (HSAS) are typically born with severe hydrocephalus and adducted thumbs (bent towards the palm). Other signs and symptoms may include:

• Seizures
• Severe intellectual disability
• Spasticity

(Source: Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius Diagnosed?

Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius?

The complications of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius may include:

• Severe brain abnormalities
• Intellectual impairment

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius Treated?

The treatment of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius (HSAS) is based on the signs and symptoms present in each person.

• Hydrocephalus is typically treated with shunt surgery
• Special education and early intervention may be recommended for children with intellectual disability
• Although intervention is rarely necessary for adducted thumbs (bent towards the palms), tendon transfer surgery or splinting may be suggested in some cases

(Source: Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius be Prevented?

Currently, Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius? (Outcomes/Resolutions)

• The prognosis of Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius:

Hydrocephalus due to Congenital Stenosis of Aqueduct of Sylvius is also known by the following names:

• Hydrocephalus, X-linked
• HSAS1
• Aqueductal stenosis, X-linked
• HSAS
• HYCX
• XLAS

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/