SNP Shot: Genomic Insights

Hereditary cerebral amyloid angiopathy (CAA) is a condition marked by the accumulation of amyloid deposits in brain blood vessels, leading to angiopathy (vascular disease). This results in progressive dementia, strokes, and other neurological issues, typically beginning in mid-adulthood. The condition often proves fatal in the sixties due to neurological decline, though the severity of symptoms varies. While most affected individuals succumb within a decade of symptom onset, some survive longer.

CAA encompasses several types, each defined by its specific genetic cause. These genetic differences influence which brain areas, beyond blood vessels, are affected, as well as the presenting symptoms. The various CAA types are often named after the geographic regions where they were initially identified.

The Dutch type of hereditary CAA is the most prevalent. Stroke is frequently the initial symptom and is fatal in roughly a third of affected individuals. Survivors often develop dementia and experience recurrent strokes. Around half of those with the Dutch type who suffer one or more strokes will also experience recurrent seizures (epilepsy).

The Flemish and Italian types of hereditary CAA are characterized by recurring strokes and dementia. Individuals with the Piedmont type may suffer one or more strokes and commonly experience impaired movement, numbness or tingling (paresthesias), confusion, or dementia.

The Icelandic type of hereditary CAA typically manifests with a stroke followed by dementia. Strokes associated with this type tend to occur earlier in life, often in the twenties or thirties.

Strokes are infrequent in individuals with the Arctic type of hereditary CAA. Memory loss, progressing to severe dementia, is typically the first sign. Strokes are also uncommon in the Iowa type, which is distinguished by memory loss, difficulties with vocabulary and speech production, personality changes, and involuntary muscle twitches (myoclonus).

Familial British dementia and familial Danish dementia, two distinct types of hereditary CAA, are characterized by dementia and movement problems. Strokes are rare in these forms. Individuals with the Danish type may also develop cataracts (clouding of the lens of the eyes) and deafness.

Inheritance:

Hereditary CAA caused by mutations in the APP, CST3, or ITM2B gene follows an autosomal dominant inheritance pattern. This means only one copy of the mutated gene in each cell is enough to cause the disorder. There is also a non-hereditary (sporadic) form of CAA that occurs in individuals without a family history of the condition. The cause of this form is currently unknown, and it is not inherited.