News & Views
Issue No. 10, 2008
The occurrence of epilepsy in Down syndrome is higher than in the general population. In this issue of News & Views, we discuss some of the details.
Down syndrome and epilepsy
By Sietske Heyn, Ph.D.
To most people, epilepsy is a mysterious brain disorder, which involves uncontrollable fits that seem to come out of nowhere. Although about 1.5-5 % of the general population has some form of epilepsy, most people know little about the disorder. Even less known is the fact that people with Down syndrome can also have epilepsy.
Epilepsy is characterized by repeated and unpredictable interruptions of normal brain function called epileptic seizures. These seizures are caused by too much, abnormal, or synchronous communication between brain cells. Many people experience one seizure sometime in their life. This does not mean that they have epilepsy. A person is diagnosed with epilepsy only when a seizure has permanently changed communication between brain cells in a way that additional seizures are likely (International league against epilepsy, 2005). Many different conditions can cause epilepsy, including illness, brain damage or abnormal brain development.
Historically, epilepsy has not been associated with Down syndrome. Investigators such as Langdon Down and others in the 19th and early 20th century did not mention epilepsy at all, and until the late 1960ies epilepsy was considered rare in people with Down syndrome (5). Today on the other hand, it is well known that epilepsy is more common in Down syndrome than in the general population (14, 9).
The exact frequency of epilepsy in Down syndrome is difficult to determine, because each study uses different definitions for epilepsy and different inclusion criteria (such as institutionalized, or home-reared, or both). More recent studies have reported a prevalence of seizures between 8% and 17 % (13; 6). This prevalence range is higher than in the general population (1.5-5%), but lower than for individuals with other forms of cognitive disabilities (14-44%) (9, 2).
In both the general population and in people with Down syndrome, epilepsy can develop at any age. However, in both populations, the onset of epilepsy is more frequent in very young children and in older adults (4, 13, 12). The biggest difference between the two populations is the age at onset in older adults: in the general population, the occurrence of epilepsy increases around age 60, whereas in the Down syndrome population, the occurrence increases around age 20-30 (4,13,12).
Early onset epilepsy
According to one study, approximately 8% of children with Down syndrome have epilepsy (5). While all major types of seizures can occur in children with Down syndrome, infantile spasms in particular are more frequent than in the general population (5,15). Partial onset seizures and generalized tonic-clonic seizures are also quite common (5).
During childhood and adolescence, the cause for epilepsy is often unknown. In some cases, it may be caused by head injuries, illness or recurring infections (15). Underlying congenital heart issues could also have an influence (5).
Late onset epilepsy
As people with Down syndrome become older, their chances of getting epilepsy increase (6,10). For example, one study found an overall epilepsy rate of 17% in adults with Down syndrome (6). However, when different age groups were analyzed separately, the rate was 8% for teenagers, 15% for young adults, and 24 % for older adults. In another study, an overall rate of 9.4 % was reported for people with Down syndrome aged 19-69 years, but the rate was 46% in people older than 50 years (10).
Why the occurrence of epilepsy increases in older individuals with Down syndrome is not clear. One explanation is the onset of Alzheimer’s disease. Many individuals with Down syndrome develop Alzheimer’s disease when they get older (7) and Alzheimer’s disease is in turn correlated with an increased rate of epilepsy (1). Individuals with Down syndrome who develop Alzheimer’s disease have epilepsy much more often than individuals who don’t show signs of Alzheimer’s disease (7).
Recently, a specific type of epilepsy has been observed in older people with Down syndrome who have dementia and Alzheimer’s disease. It is called late onset myoclonic epilepsy (LOMEDS) (11) or senile myoclonic epilepsy of Genton (3) and resembles a type of epilepsy known as Unverricht-Lundborg disease. Interestingly, both the gene for Unverricht Lundborg disease and the APP gene, which is involved in Alzheimer’s disease, are located on chromosome 21. Some researchers have suggested that LOMEDS may be a distinct type of epilepsy caused by the extra genes on the third copy of chromosome 21 (3).
The take home message
People with Down syndrome have epilepsy more often than people without Down syndrome. Why epilepsy is more common in people with Down syndrome is not clear, but it is likely due to structural and functional abnormalities in the brain caused by the extra chromosome 21. Associated medical complications such as cardiovascular abnormalities and recurrent infections might also influence the likelihood of getting epilepsy (5).
There appear to be two peaks in the onset of epilepsy: one in the first year of life and one in older adults. Peak 1 is mostly associated with an increased occurrence of infantile spasms, while peak 2 is associated with mental decline and onset of Alzheimer’s disease.
Early detection of epilepsy is essential for successful treatment and to avoid cognitive regression, especially due to early onset epilepsy. Awareness of the association between Down syndrome and epilepsy is important so that doctors can intervene early to maximize development and to improve the quality of life (5).
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