What is Kearns-Sayre syndrome and what are its symptoms?

Kearns-Sayre Syndrome: Definition and Clinical Features

Kearns-Sayre syndrome (KSS) is a rare mitochondrial genetic disorder characterized by the classic triad of chronic progressive external ophthalmoplegia (drooping eyelids and paralysis of eye muscles), pigmentary retinopathy (abnormal retinal pigmentation), and onset before age 20 years. 1

Core Diagnostic Features

The diagnosis requires all three of the following cardinal features:

• Progressive external ophthalmoplegia - paralysis of the muscles controlling eye movement, leading to inability to move the eyes in various directions 1
• Pigmentary retinopathy - characteristic "salt and pepper" appearance of the retina due to abnormal pigment deposition 1, 2
• Onset before 20 years of age - symptoms must begin during childhood or adolescence 2, 3

Cardiac Manifestations (Life-Threatening)

Cardiac conduction disease is the most critical and life-threatening manifestation of KSS, as it determines the vital prognosis and is a major cause of sudden cardiac death. 4, 5

• Progressive His-Purkinje disease develops in many patients, leading to high-grade atrioventricular (AV) block 1
• Complete heart block is the most common cardiac complication, occurring in approximately 50% of patients with KSS 5, 6
• Bradycardia-related polymorphic ventricular tachycardia can occur as conduction disease progresses 5
• Sudden cardiac death is a recognized complication, even with pacemaker implantation 1

Additional Systemic Manifestations

Neurological Features

• Cerebellar ataxia - impaired coordination and balance 1, 3
• Elevated cerebrospinal fluid protein (>100 mg/dL) 1
• Dementia and cognitive decline 2
• Bilateral sensorineural deafness 2, 3
• Dystonia and movement disorders 2
• Bulbar symptoms including dysarthria (speech difficulty) and nasal regurgitation 2
• Bilateral facial weakness 2

Endocrine Abnormalities

• Diabetes mellitus 2, 3
• Growth retardation and short stature 2, 3
• Hypoparathyroidism with associated hypocalcemia 2, 3
• Hyperaldosteronism 3

Musculoskeletal Features

• Skeletal muscle weakness - proximal muscles more affected than distal 2
• Exercise intolerance due to mitochondrial dysfunction 2
• Myopathy with variable number of "ragged-red fibers" on muscle biopsy (a pathognomonic finding) 2

Renal Manifestations

• Proximal renal tubular acidosis (de Toni-Debré-Fanconi syndrome) 2, 3
• Hyperphosphaturia, hyperaminoaciduria, and glucosuria indicating progressive renal tubular insufficiency 3

Ophthalmologic Features Beyond the Triad

• Cataracts 2
• Bilateral ptosis (drooping eyelids) 2, 4

Genetic Basis

• Large-scale single deletions or rearrangements of mitochondrial DNA (mtDNA) are the underlying cause 2
• Sporadic occurrence - usually not inherited but occurs spontaneously at the germ-cell level or very early in embryonic development 2
• The condition is classified as a mitochondrial cytopathy affecting multiple organ systems 1, 5

Clinical Management Priorities

Permanent pacing is reasonable in patients with Kearns-Sayre syndrome and conduction disorders, with additional defibrillator capability if appropriate and meaningful survival of greater than 1 year is expected. 1, 7

• Systematic cardiac assessment is essential as cardiac involvement determines prognosis 4
• No disease-modifying therapy is currently available; management is entirely supportive 2
• Vigilance for detection of associated problems across multiple organ systems is required 2

Common Diagnostic Pitfall

The diagnosis is often delayed for several years until multiple manifestations become apparent, particularly when patients present initially with isolated symptoms such as diabetes mellitus or cardiac conduction abnormalities. 3 Clinicians should maintain a high index of suspicion for KSS in any young patient presenting with progressive external ophthalmoplegia, even before the full triad is evident. 4, 3