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

• Familial Cerebral Amyloid Angiopathy
• Genetic Cerebral Amyloid Angiopathy
• HCHWA (Hereditary Cerebral Hemorrhage with Amyloidosis)

What is Hereditary Cerebral Hemorrhage with Amyloidosis? (Definition/Background Information)

• Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA) is a neurological condition in which an abnormal protein (amyloid) builds up in the walls of the arteries of the brain (and less frequently, veins)
• This process is known as amyloid deposition, which can lead to strokes, seizures, neurological deficits, cognitive decline, and dementia. Symptoms usually present before the 5th decade of life
• There are many different ways of classifying the types of Hereditary Cerebral Hemorrhage with Amyloidosis based on the underlying genetic changes, proteins involved, signs and symptoms, and the regions in which they were first described
• Based on the region in which they were first described, the subtypes include:
  • The Dutch, Arctic, Piedmont, Iowa, Flemish, Italian types are caused by mutations in the APP gene
  • The British and Danish types are caused by mutations in the ITM2B gene
  • The Icelandic type is caused by mutations in the CST3 gene 
• All types of HCHWA currently described are inherited in an autosomal dominant manner
• There is no cure for Hereditary Cerebral Hemorrhage with Amyloidosis; however, antihypertensive therapy is typically recommended

(Source: Hereditary Cerebral Hemorrhage with Amyloidosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hereditary Cerebral Hemorrhage with Amyloidosis? (Age and Sex Distribution)

• Hereditary Cerebral Hemorrhage with Amyloidosis is a rare inherited disorder, reported in about 300-400 families worldwide
• The presentation of symptoms occurs in adulthood, before the age of 50
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected. Some geographical regions are known to show a higher incidence of the condition than others

What are the Risk Factors for Hereditary Cerebral Hemorrhage with Amyloidosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hereditary Cerebral Hemorrhage with Amyloidosis can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

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 Hereditary Cerebral Hemorrhage with Amyloidosis? (Etiology)

• Hereditary Cerebral Hemorrhage with Amyloidosis may be caused by mutation(s) in APP, ITM2B or CST3 gene, coding for amyloid precursor protein, integral membrane protein 2B and cystatin C proteins, respectively
• The disorder is inherited in an autosomal dominant manner

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Hereditary Cerebral Hemorrhage with Amyloidosis?

The signs and symptoms of Hereditary Cerebral Hemorrhage with Amyloidosis may include:

• Cerebellar hemorrhage
• Cerebral amyloid angiopathy
• Cerebral ischemia
• Dementia
• Recurrent cerebral hemorrhage
• Stroke
• Tortuous cerebral arteries

(Source: Hereditary Cerebral Hemorrhage with Amyloidosis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hereditary Cerebral Hemorrhage with Amyloidosis Diagnosed?

Hereditary Cerebral Hemorrhage with Amyloidosis 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
• Molecular genetic testing to check for or confirm causative gene mutation(s)

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 Hereditary Cerebral Hemorrhage with Amyloidosis?

The complications of Hereditary Cerebral Hemorrhage with Amyloidosis may include:

• Seizures, with increased risk of falls and injury
• Paralysis, which may affect muscle functions in the face and mouth
• Progressive dementia

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

How is Hereditary Cerebral Hemorrhage with Amyloidosis Treated?

There is no cure for Hereditary Cerebral Hemorrhage with Amyloidosis, since it is a genetic condition.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• Anti-hypertensive drugs may be recommended in some cases.

How can Hereditary Cerebral Hemorrhage with Amyloidosis be Prevented?

Currently, Hereditary Cerebral Hemorrhage with Amyloidosis may not be preventable, since it is a genetic disorder.

• If there is a family history of the condition, then genetic counseling will help assess risks
• 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 Hereditary Cerebral Hemorrhage with Amyloidosis? (Outcomes/Resolutions)

• The prognosis of Hereditary Cerebral Hemorrhage with Amyloidosis is generally poor, since it is associated with worsening signs and symptoms
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hereditary Cerebral Hemorrhage with Amyloidosis:

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

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