Progressive myoclonic epilepsy type 1

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Progressive myoclonic epilepsy type 1 (also called Unverricht-Lundborg disease or ULD) is a rare inherited form of epilepsy. Early development is normal in affected individuals. Signs and symptoms of the disorder typically begin between 6 and 15 years of age.

People with progressive myoclonic epilepsy type 1 experience episodes of involuntary muscle jerking or twitching (myoclonus) that increase in frequency and severity over time. Episodes of myoclonus may be brought on by physical exertion, stress, light, or other stimuli. Within 5 to 10 years, the myoclonic episodes may become severe enough to interfere with walking and other everyday activities.

Affected individuals also usually have seizures that involve loss of consciousness, muscle rigidity, and convulsions (tonic-clonic or grand mal seizures). Like the myoclonic episodes, these may increase in frequency over several years. However, the seizures may be controlled with treatment. After several years of progression, the frequency of seizures may stabilize or decrease.

Eventually, people with progressive myoclonic epilepsy type 1 may develop problems with balance and coordination (ataxia) and speaking (dysarthria). They may also experience depression. Another feature of this condition is involuntary rhythmic shaking. This shaking is called intentional tremor because it worsens during intentional movements.

People with progressive myoclonic epilepsy type 1 may live into adulthood. Life expectancy depends on the severity of the condition and a person's response to treatment. The severity of the condition can vary, even among members of the same family.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the CSTB gene cause progressive myoclonic epilepsy type 1. The CSTB gene provides instructions for making a protein called cystatin B. This protein reduces the activity of enzymes called cathepsins. Cathepsins help break down certain proteins in the lysosomes, which are compartments in the cell that digest and recycle different types of molecules. While the specific function of cystatin B is unclear, it may help protect the cells' proteins from cathepsins that leak out of the lysosomes.

In almost all affected individuals, progressive myoclonic epilepsy type 1 is caused by variants that affect the amount of cystatin B that is produced. One region of DNA that controls the activity of the CSTB gene has a particular repeating sequence of 12 DNA building blocks (nucleotides). This sequence is known as the dodecamer repeat. Normally, this sequence is repeated two or three times. However, in most people with progressive myoclonic epilepsy type 1, this sequence is repeated more than 30 times (called a repeat expansion). Most people with progressive myoclonic epilepsy type 1 have two copies of this variant.

A small number of people with progressive myoclonic epilepsy type 1 have one copy of the dodecamer repeat expansion and one copy of the CSTB gene with another type of variant. These other variants can include the substitution of a single nucleotide that impairs the gene's function.

In individuals with progressive myoclonic epilepsy type 1, levels of cystatin B are only 5 to 10 percent of normal. This change is believed to cause the signs and symptoms of progressive myoclonic epilepsy type 1, but it is unclear how a reduction in the amount of cystatin B leads to the features of this disorder.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Progressive myoclonus epilepsy is a rare group of conditions. Progressive myoclonic epilepsy type 1 is believed to be the most common form of this type of epilepsy, but its worldwide prevalence is unknown. The condition is more common in the North African countries of Tunisia, Algeria, and Morocco. Progressive myoclonic epilepsy type 1 occurs most frequently in Finland, where approximately 2 in 100,000 people are affected.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

EEG with polyspike wave complexes · Very frequent (99-80%)

The presence of complexes of repetitive spikes and waves in EEG.

Limb ataxia · Very frequent (99-80%)

A kind of ataxia that affects movements of the extremities.

Myoclonus · Very frequent (99-80%)

Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.

Morning myoclonic jerks · Very frequent (99-80%)

Ataxia · Frequent (79-30%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Dysarthria · Frequent (79-30%)

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

Intention tremor · Frequent (79-30%)

A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).

Cutaneous photosensitivity · Occasional (29-5%)

An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

Other findings in the same source

From: Orphanet

Additional reported features include Dementia (Occasional (29-5%)); Intellectual disability (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Progressive myoclonic epilepsy type 1 is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.