What Is LHON Plus and Which Symptoms Can It Cause?

Leber hereditary optic neuropathy (LHON) typically causes vision loss in both eyes. However, “LHON Plus” is a term used to describe when a person with an LHON pathogenic genetic variant experiences additional neurological or systemic (whole-body) symptoms ^[1][2]. It is important to know that LHON Plus is not a single, predictable diagnosis; it is a descriptive term for a spectrum of possibilities. Having an LHON-associated genetic variant does not automatically mean you will develop LHON Plus, and many people will not experience these extra features ^[3].

Because LHON is a mitochondrial disease—meaning it involves a genetic change in the mitochondrial DNA that affects how cells produce energy—tissues that require a vast amount of energy, like the brain, nerves, muscles, and heart, are most vulnerable ^[4][5].

When to Seek Immediate Care
Do not wait for a routine specialist visit if you experience sudden, severe symptoms. Seek emergency medical evaluation for chest pain, fainting, sustained racing heart (palpitations), a new seizure, rapid onset of muscle weakness, or sudden severe vision changes.

What Are the Extra Symptoms?

The list below represents possibilities drawn from clinical reports and case studies. It is not a checklist of what will happen to any individual, and the frequency of these symptoms varies. Importantly, any new symptom should be evaluated by a doctor to rule out other common, treatable causes before assuming it is LHON Plus ^[6].

More Commonly Established Features:

• Movement and Coordination: Tremors and dystonia (involuntary muscle contractions that cause repetitive movements or abnormal postures) are among the most frequently documented extra-ocular symptoms ^[7][8].
• Nerve and Muscle Symptoms: Some individuals experience peripheral neuropathy (numbness, tingling, or pain in the hands and feet) or myopathy (muscle weakness) ^[8][9].
• Heart Conduction Issues: Cardiac electrical rhythm changes (arrhythmias) or conduction abnormalities (such as a shortened PR interval on a heart monitor) can occur ^[8][10].

Rare Reported Features:

• In very rare instances, individuals have experienced seizures, significant balance problems (ataxia), or spinal cord inflammation (transverse myelitis) ^[8][11].
• Structural heart differences and hearing loss are also uncommon but have been reported in the medical literature ^[12][10].

Genetic Variants: What They Mean For You

LHON is passed down through maternal inheritance (from mother to child). LHON Plus can happen with the most common LHON genetic variants, such as m.11778G>A and m.3460G>A ^[13][14]. However, some rarer mitochondrial DNA variants, like m.14459G>A (often affecting the MT-ND6 gene) and m.10197G>A, are more strongly linked to movement disorders and other neurological signs ^[7][15][16].

Your genetic result is a piece of the puzzle, not a crystal ball. A variant does not predict your specific clinical outcome due to incomplete penetrance (meaning not everyone with the gene develops the trait). A genetic counselor can help interpret what your results mean for you and your maternal relatives ^[3].

Building Your Care Team and Monitoring

If you have LHON or an LHON-associated variant, your care plan should be personalized to your symptoms and genetic profile:

• Heart Monitoring: Because cardiac conduction issues can occur, a baseline electrocardiogram (ECG) is often discussed. However, the need for an ECG, an echocardiogram (ultrasound of the heart), or repeated monitoring depends on your specific symptoms, family history, and your clinician’s guidelines ^[10].
• Neurological Care: A neurologist can help evaluate and treat movement disorders or nerve issues. While there is no single treatment for LHON Plus, specific manifestations—such as dystonia, seizures, or neuropathic pain—have their own symptom-specific treatment plans that can improve quality of life ^[2].
• Care Coordination: Your care team may expand beyond a neuro-ophthalmologist to include a neurologist, cardiologist, or mitochondrial disease specialist. Always ensure they communicate with one another so your care is comprehensive.