MERRF syndrome (m.8344A>G): myoclonic epilepsy, maternal inheritance and care

MERRF stands for myoclonic epilepsy with ragged red fibres. The last part of the name refers to the appearance of muscle fibres under the microscope in a muscle biopsy, where abnormal clusters of mitochondria give a ragged look. The glossary of the NHS Rare Mitochondrial Disorders Service describes it as a particular mitochondrial disease caused by a mutation in mitochondrial DNA.

The mitochondria in each cell make the energy that tissues need. When a large share of the mitochondrial DNA in a person carries the MERRF variant, tissues with high energy demand such as brain and muscle do not work as well, and the neurological features follow.

The service notes that MERRF belongs to the group of mitochondrial DNA diseases that can be inherited maternally, alongside Leigh syndrome, MELAS, MIDD, NARP and LHON.

The service says the features are predominantly neurological. Many patients develop myoclonic epilepsy. A myoclonic jerk is a brief, sudden jerk that often happens first thing in the morning, and jerks can come in a run. They are sudden in onset and not necessarily associated with a loss of consciousness. Some patients also have generalised tonic-clonic seizures.

There can be quite marked muscle weakness, for example difficulty getting up from a squatting position or difficulty drying or washing hair. Unsteadiness, called ataxia, can make walking tricky and fine tasks at home harder, although the service stresses that it is not present in many patients. A slight loss of short-term memory can occur in people with more severe disease.

Some patients develop fat deposits, called lipomas, in and around the back of the neck. The service says this feature is usually only seen in people with the 8344A>G variant. The service describes mitochondria as present in every tissue, so regular checks across several body systems, including the heart, are part of care in mitochondrial disease.

Every cell contains many copies of mitochondrial DNA, and in people with MERRF there is a mixture of normal and changed copies. The service explains that people with high amounts of the abnormal DNA are much more likely to develop symptoms than those with only a very small amount.

This mixture is the reason that two relatives with the same variant may look very different. One may have no symptoms at all while another has epilepsy, weakness and unsteadiness. It also explains why the severity in a mother does not reliably predict the severity in her children.

Mitochondrial DNA is inherited from mothers only. The service explains that in maternally inherited mitochondrial DNA disease all of the mother's children may carry the variant, but some may be severely affected and others not affected, because the level of changed DNA passed on varies.

A man with the variant cannot pass it to his children. A woman can pass it to sons and daughters, and daughters can in turn pass it on. A small number of mitochondrial DNA changes arise for the first time in a person and are not inherited, but the service lists MERRF with the conditions that are usually maternally inherited.

Relatives on the maternal side, including brothers, sisters and the mother's own siblings, may carry the same variant. A clinical genetics or mitochondrial service can arrange testing and explain what a result means.

Doctors begin with the clinical picture of jerks, seizures, ataxia and weakness, often with a family history on the mother's side. The service explains that blood and urine tests can look for high lactate, although many patients with mitochondrial disease have normal blood lactate, so these tests give clues rather than answers.

Genetic testing is the key test. The service says that the common mitochondrial DNA changes of well-described conditions such as MERRF and Leber hereditary optic neuropathy can be detected easily in blood, and that this is the tissue most centres investigate. If the variant is not found, a muscle biopsy may be helpful because some changes are only detectable in muscle.

Brain imaging with MRI and an EEG are used to assess the brain and the seizures. Best practice guidance on genetic testing for mitochondrial disease has been published by the NHS Highly Specialised Service for Rare Mitochondrial Disorders, which has centres in London, Newcastle and Oxford.

The service says treatment for MERRF is about minimising the impact of the disease on people's lives. It is important that seizures, both the myoclonic jerks and the tonic-clonic seizures, are adequately treated. The myoclonic jerks are probably best treated with lamotrigine or levetiracetam, and the service says it does not advise sodium valproate, which is used for myoclonic seizures due to other conditions.

At present there is relatively little that can be done for the unsteadiness and muscle weakness, so appropriate aids in the home are recommended. More generally, the service describes regular monitoring, including blood tests for problems such as diabetes, an ECG to check the heart, and EEG when seizures are a feature, because many complications can be treated effectively if found early.

Exercise at a comfortable level is encouraged to avoid deconditioning, alcohol should be taken in moderation, and a person with a mitochondrial diagnosis should tell any anaesthetist before an operation.

The service says that the final decision on driving lies with the DVLA and that it is up to the patient to tell the DVLA about conditions that may affect driving. It states that if you have an epileptic seizure you cannot drive for at least six months, but that additional seizures or a predisposing factor such as MELAS or MERRF make a one-year period more likely.

The service also covers benefits, employment and education in its general advice, and recommends discussing cognitive or mood difficulties with a GP or neurologist, as a neuropsychology assessment may help.