Kearns–Sayre syndrome

Overview

Kearns–Sayre syndrome (KSS) is a rare neuromuscular disorder caused by defects in mitochondrial DNA. It primarily affects the eyes, muscles, and heart, typically presenting before the age of 20. The hallmark features of KSS include progressive external ophthalmoplegia (weakness of the eye muscles), pigmentary retinopathy, and cardiac conduction abnormalities. As a mitochondrial disorder, KSS impacts cells that require high energy, particularly those in the nervous system, muscles, and eyes.

Causes

Kearns–Sayre syndrome is caused by deletions in mitochondrial DNA (mtDNA). Unlike nuclear DNA, mtDNA is inherited exclusively from the mother. Most cases of KSS arise from spontaneous (de novo) deletions rather than being inherited. These deletions impair mitochondrial function, reducing the ability of cells to generate energy efficiently. As a result, tissues with high energy demands are most affected.

Symptoms

The clinical presentation of KSS varies but often includes the following key symptoms:

• Progressive external ophthalmoplegia: Gradual paralysis of eye muscles leading to restricted eye movement

• Ptosis: Drooping of the eyelids

• Pigmentary retinopathy: A characteristic speckled appearance of the retina, often leading to visual disturbances

• Cardiac conduction defects: Heart block or arrhythmias, which can be life-threatening

• Muscle weakness and exercise intolerance

• Hearing loss

• Short stature

• Endocrine disorders such as diabetes mellitus or hypothyroidism

• Neurological issues such as ataxia or cognitive impairment (in some cases)

Symptoms usually begin in childhood or adolescence and progressively worsen over time.

Diagnosis

Diagnosis of Kearns–Sayre syndrome is based on clinical features, imaging studies, and genetic testing. Key diagnostic steps include:

• Clinical evaluation of muscle weakness, eye movement, and visual function

• Ophthalmologic examination showing pigmentary retinopathy and ophthalmoplegia

• Electrocardiogram (ECG) or Holter monitoring to detect cardiac conduction abnormalities

• Muscle biopsy revealing ragged red fibers (a hallmark of mitochondrial myopathies)

• Blood and cerebrospinal fluid tests showing elevated lactate and pyruvate levels

• Mitochondrial DNA testing to detect large-scale deletions

An early and accurate diagnosis is critical to managing complications, particularly cardiac issues.

Treatment

There is no cure for Kearns–Sayre syndrome, and treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is essential. Key treatment strategies include:

• Cardiac management: Regular monitoring and implantation of a pacemaker for individuals with conduction block or arrhythmias

• Ophthalmologic support: Surgical correction of ptosis and visual aids for vision impairment

• Physical therapy: To maintain muscle strength and mobility

• Hearing aids: For sensorineural hearing loss

• Endocrine treatment: Management of diabetes, hypothyroidism, or other hormonal issues as needed

• Vitamin and supplement therapy: Coenzyme Q10, L-carnitine, and other mitochondrial support supplements are often prescribed, though their effectiveness varies

Prognosis

The prognosis of Kearns–Sayre syndrome depends on the severity and progression of organ involvement, particularly the heart. Cardiac complications are the most serious and can be fatal if not properly managed. With vigilant cardiac monitoring and pacemaker implantation when necessary, many individuals can live into adulthood. However, the condition is progressive, and patients often experience worsening neuromuscular and visual function over time. Supportive care can improve quality of life and prolong survival.