What is it like?

Patients with Unverricht-Lundborg have myoclonic movements associated with voluntary body movement (physical exertion) or other stimuli, such as periodic flashes of light (photic sensitivity), noises (auditory induced myoclonus), and stress. Myoclonic movements are quick muscle movements or jerks involving particular muscles. The quick jerks may involve a single muscle, a small group of related muscles, or large groups of muscles. In addition, other activities which have been linked to episodes of myoclonus in people with Unverricht-Lundborg include talking and or doing calculations.

Unverricht-Lundborg disease has a slow progressive worsening of symptoms, both in seizure control and neurological functioning. The disease progresses slowly, with patients maintaining normal cognitive functioning for a long time and decline in intelligence being very slow. Moderate deterioration may take from 10 to 20 years. Most patients live 50 – 60 years before dying.

What is Unverricht Lundborg disease?

Unverricht-Lundborg disease is the most common of an uncommon group of genetic epilepsy disorders--the progressive myoclonic epilepsies. Unverricht-Lundborg disease is an autosomal recessive inherited disorder. Recessive inheritance occurs when BOTH genes of a pair are abnormal, thus producing the disease. In other words, in autosomal recessive inheritance both parents are carriers of the abnormal gene, which in this case is Unverricht-Lundborg. The gene for Unverricht-Lundborg disease is located on chromosome 21. This chromosome is one of the 22 pairs of chromosome in each cell that are not associated with determination of sex (sex chromosomes). Genes found on these chromosomes are responsible for genetic disorders, described as recessive and dominant.

Studies have shown that approximately 1 person in 20,000 in Finland has the epilepsy disorder. Although the disease is found in other areas, it is less common in other populations around the world, in particular, the United States, Canada, and northern Europe. In addition, there does not seem to be a difference in the number of girls versus boys that inherit Unverricht-Lundborg.

Who gets it?

The typical patient is a previously healthy child, between the ages of 6 to 18, who begins to manifest involuntary, action-activated myoclonic jerks and/or generalized tonic-clonic seizures. In almost half of the children, the presenting symptom is a generalized tonic-clonic seizure. The severity of the symptoms and the rate of progression are variable, both between and within families.

How is Unverricht-Lundborg disease Diagnosed?

The diagnosis is made by the clinical presentation of the disease. A normal child develops stimulus sensitive myoclonus, epilepsy, and progressive neurologic deterioration between the ages of 6 and 18 years. The diagnosis of Unverricht-Lundborg can be confirmed by identifying the disease-causing abnormalities in the EPM1 gene. The DNA code or sequence of nucleic acid bases that make up the gene is found to have a sequence of 12 base pairs that is repeated from 30 to over 100 times. Over 90% of patients with Unverricht-Lundborg disease have this repeated sequence of DNA as the cause of their disease. Other patients have one of three mutations within the gene itself and not the 12 base pairs that repeat multiple times. However, these latter patients are in the minority.

Tell me more

This disorder was first described by Dr. Unverricht in 1891 in Estonia and Dr. Lundborg in Sweden in 1903, hence the name of the disease. This disorder has also been called Baltic myoclonus, Mediterranean myoclonus, and Progressive myoclonus epilepsy 1 (EPM1). The terms Baltic myoclonus and Mediterranean myoclonus arose from descriptions of patients having myoclonus and progressive intellectual decline. Initially, although having the same symptoms as Unverricht Lundborg disease, they were thought to be separate diseases. However, the abnormal gene has been found to be the same in each of the disorders. This indicates that the diseases are actually the same and all are now considered a single disease. The gene is named EPM1 and is located on chromosome 21. Unverricht-Lundborg disease is also called EPM1 for the gene involved in causing the disease.

How is it treated?

Antiepileptic Medications

The most reliable seizure medication for seizure and myoclonus control is valproic acid, which decreases myoclonus and the frequency of generalized seizures. Clonazepam and piracetam are effective as add-on therapy to valproic acid. However, piracetam is not available in the United States.

Some of the newer medications such as levetiracetam, lamotrigine, topiramate and zonisamide, may reduce seizure frequency, but are not as well studied as valproic acid and clonazepam. It is important to note that some medications are completely ineffective in the treatment of Unverricht-Lundborg disease such as phenytoin and carbamazepine. In fact, phenytoin is believed to worsen the course of Unverricht-Lundborg.

Surveillance: Clinical and Psychosocial Evaluation

Once the diagnosis has been confirmed, clinical evaluation of walking, coordination, handwriting, school performance, and emotional well-being are essential in monitoring the progression of the disease. Furthermore, the patient’s education is often interrupted due to emotional, social, and intellectual problems therefore, school performance may be affected. Also, psychological therapy may be needed for emotional issues, which are commonly associated with the disease, and is especially true during the teenage years. Some experts recommend clinical and psychosocial follow-up at 6-month intervals for teenage patients. Suicide is increased in patients with Unverricht-Lundborg disease and close watch of depression should be performed.

What is the outlook?

Unverricht-Lundborg differs from other forms of progressive myoclonic epilepsies in that it is chronic and debilitating, but not fatal. The other types of progressive myoclonic epilepsies are fatal, with death occurring between 3 to 40 years from onset. With modern medication and therapy of psychosocial and physical rehabilitation, individuals may live into their sixties or seventies.

There is some suggestion that early diagnosis and administration of valproic acid after the onset of symptoms may delay or even slow the progression of the disease. Although the natural course of this disorder is highly variable, early detection by genetic testing may help in early treatment.

Some years after disease onset, uncoordinated movements, loss of smooth intentional muscle movements, tremor with movement, and difficultly in articulation of speech are handicapping and therapy to address these issues is important. Also, patients with this disorder are mentally alert, but show emotional instability and depression. Therefore, psychotherapy can help individuals cope with their disease. It is important for parents to plan for the long term care of their children, early in the course of the disease.

Topic Editor: Russell P. Saneto, D.O., Ph.D.
Last Reviewed: 3/30/05