Epilepsy/Seizures and Down Syndrome
Introduction
Seizures often occur in association with other disorders. A seizure is a sudden burst of electrical activity in the brain that results in the loss of control of the body by the brain. This poses a potential challenge for individuals living with multiple disorders. A lack of information about multiple disorders may lead to confusion and uncertainty for these individuals. Therefore, this pamphlet focuses on Down syndrome associated with seizures. It presents information about Down syndrome and how it relates to epilepsy. This cross-diagnosis summary was created to facilitate healthcare providers in providing complete and comprehensive information to the public. For more in depth information about Down syndrome and/or epilepsy, please contact the appropriate association or consult your physician/neurologist (3).
Down syndrome (DS, trisomy 21) is the most common chromosomal cause of mental retardation, with an incidence of approximately 1 per 1,000 live births. People with DS are at risk for congenital cardiac anomalies, duodenal obstruction, immunologic compromise, infections, leukaemia and complications of other organ systems. Neurologically, DS is universal, with declining developmental quotients with age, however there is a wide variation in cognitive level and outcomes are better with directed training and home care. DS is the prototype disorder of cerebral (central) hypotonia [diminished tone of the skeletal system; a sign of weakness and floppiness in babies due to nonprogressive weakness of skeletal muscles from birth], which results in a delayed acquisition of motor skills. In the fourth decade of life, all persons with DS develop clinical and neuropathologic signs of Alzheimer's disease (1).
General Information About Epilepsy/Seizures and Down Syndrome
Seizures occur in 5% to 10% of persons with DS, which is several times the expected frequency in the general population. The high frequency of seizures in DS is likely due to a combination of inherent physiological and structural anomalies (brain dysgenesis) and common medical complications of the syndrome. Also, there is an age-related incidence of epilepsy in DS, peaking in the first year, and again in the fourth and fifth decades of life. Approximately 75% of older DS individuals develop seizures (1).
What Types of Seizures Occur in Individuals with Down Syndrome?
All seizure types are represented in DS, with generalized tonic-clonic seizures being the most common. Reflex seizures, precipitated by sensory stimuli, are also frequently seen. However, febrile seizures are surprisingly uncommon in people with DS. In addition, there are no characteristic EEG changes in people with DS to aid in the classification of seizure mechanisms. In many DS individuals, the EEG is normal or displays nonspecific background changes (1).
Why do Some Children with Down Syndrome Have Seizures?
Some seizures are associated with a specific problem, such as cardiovascular disease. However, many seizures have no association with any other clinical condition. One answer to the above question lies somewhere in the balance in the brain between the "excitatory" and "inhibitory" pathways. There are four different ways that this could happen:
• Decreased inhibition of the electrical pathways;
• Increased excitation of the brain cells;
• Structural abnormalities of the brain leading to electrical overstimulation;
• Changes in the amounts of neurotransmitters (the chemicals made by brain cells to send signals to each other or fire electrical impulses).
Although these can be reasons for seizures, not all children with DS have seizures; thus, there must be more involved in the process, and further studies are needed (2).
What is a Typical Seizure for a Person with Down Syndrome?
Seizures of individuals with DS commonly look like epileptic seizures: jerking of arms and legs, and loss of consciousness. Seizures can also take a mixed form, with staring spells and momentary lapses of attention (2).
Genetics and Down Syndrome
DS is usually associated with triplication of chromosome 21 in 95% of cases, and the remainder being caused by a chromosomal translocation [removal of a chromosome from one place to another] (4%) or mosaicism [the presence in an individual of two or more cell lines that are genetically distinct and are derived from a single fertilized ovum] of a trisomic cell line (1%). The full DS appearance (phenotype) such as mental retardation, characteristic facies [the anterior, or ventral, aspect of the head, from forehead to chin], limb and dermatoglyphic anomalies appear to manifest when chromosome 21 (band 21q22) is triplicated. Compared with normal brains, DS brains are smaller with a more globular shape. Further, genetic mapping has localized the gene for progressive myoclonic epilepsy (abrupt muscle jerks in part or all of the body) on the distal long arm of chromosome 21, within the critical DS region. It is possible that this gene product is the cause of the increased risk of myoclonic seizure disorders in people with DS (1).
Resources
(1) Sillanpaa, Matti, et al. Epilepsy and Mental Retardation. Philadelphia: Wrightson Biomedical Publishing Ltd., 1999.
(2) Stafstrom, CE, et al. "Seizures in Children with Down Syndrome: Etiology, Characteristics and Outcome". Devel Med Child Neuro 33: 191-200, 1991.
(3) Epilepsy Ontario. "Cross Diagnosis of Epilepsy." 20 Aug. 2002 <
http://www.epilepsyontario.org>
Thanks to HRDC (Human Resource Development Canada) Summer Career Placement Program, and to Theresa Sargeson for her work in researching and creating this project.
