Hydrocephalus due to congenital stenosis of aqueduct of sylvius

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:^[1][2]

• Seizures
• Severe intellectual disability
• Spasticity

Of note, HSAS is one form of L1 syndrome, which is an inherited condition that primarily affects the nervous system. Other forms include MASA syndrome, X-linked complicated hereditary spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis. All of the different forms of L1 syndrome may be observed in affected people within the same family.^[1] GeneReviews offers more specific information about the signs and symptoms associated with each form of L1 syndrome. Please click on the link to access this resource.

Hydrocephalus due to congenital stenosis of aqueduct of sylvius is inherited in an X-linked recessive manner.^[3] 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.

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.^[1]

The treatment of hydrocephalus due to congenital stenosis of aqueduct of sylvius (HSAS) is based on the signs and symptoms present in each person. For example, 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.^[1][2]