Diagnostic Criteria

Clinical diagnostic criteria for MERRF (myoclonic epilepsy with ragged red fibers) have been published .

Suggestive Findings

MERRF (myoclonic epilepsy with ragged red fibers) should be suspected in individuals with the following features.

Clinical features

• Myoclonus

• Generalized epilepsy

• Ataxia

• Myopathy

• Exercise intolerance

• Dementia

• Ptosis

• Sensorineural hearing loss

• Short stature

• Optic atrophy

• Peripheral neuropathy

Less common clinical signs (seen in 50% of affected individuals) include the following:

• Cardiomyopathy

• Pigmentary retinopathy

• Pyramidal signs

• Ophthalmoparesis

• Multiple lipomas

Laboratory features

Source: GeneReviews — "MERRF"

Differential Diagnosis

Neurologic findings. The differential diagnosis includes other mitochondrial disorders (see Mitochondrial Disorders Overview), syndromes characterized by ataxia (see Hereditary Ataxia Overview) and myoclonus epilepsy (e.g., Unverricht-Lundborg disease, Lafora type progressive myoclonus epilepsy, neuronal ceroid lipofuscinoses, and sialidosis ), and the disorders summarized in . The multisystem involvement, lactic acidosis, evidence of maternal inheritance, and muscle biopsy with RRF (ragged red fibers) distinguish MERRF (myoclonic epilepsy with ragged red fibers) from other conditions. Table 4. Genes of Interest in the Differential Diagnosis of MERRF

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MERRF (myoclonic epilepsy with ragged red fibers), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with MERRF

Source: GeneReviews — "MERRF"

Clinical Guidance

Individuals with MERRF should avoid mitochondrial toxins such as aminoglycoside antibiotics, linezolid, cigarettes, and alcohol. Valproic acid should be avoided in the treatment of seizures.

Source: GeneReviews — "MERRF"

Therapies Under Investigation

Mitochondrial replacement therapy (MRT) – replacement of a woman's abnormal mitochondrial DNA with healthy mitochondrial DNA from a donor – has been under investigation as a way to prevent these disorders from continuing in a family. MRT includes three types of techniques: spindle transfer, pronuclear transfer, and polar body transfer. MRT was successfully approved by the United Kingdom Parliament and a clinical trial is under way. To date, these techniques are not approved in the United States. Genetic therapy through the delivery of mitochondrially targeted zinc finger nucleases delivered by an adeno-associated virus has been studied in mouse models with mitochondrial disorders. The mutational load decreased by 20% in treated animals, and biochemical phenotypes were reversed .

Source: GeneReviews — "MERRF"

Surveillance Guidelines

Affected individuals and their at-risk relatives should be followed at regular intervals (e.g., every 6-12 months initially) to monitor progression of disease and the appearance of new symptoms.

Table 7.

Recommended Surveillance for Individuals with MERRF

System/Concern | Evaluation | Frequency

Neurologic

| Neurologic exam | • Annually

• If normal for 3 yrs, less frequent evals can be considered.

Eyes | Ophthalmologic exam

Cardiovascular

| • Electrocardiogram

• Echocardiogram

Endocrinologic

| • Fasting blood sugar

• TSH

Hearing

| Audiologic eval | Every 2-3 yrs

TSH = thyroid stimulating hormone

Source: GeneReviews — "MERRF"