Case Study
A 17-year-old male presented with progressive bilateral drooping of the eyelids since early childhood.
His parents noted that he had difficulty keeping his eyes open, especially in dim lighting, and frequently adopted a chin-up posture to compensate.
He also had a history of muscle weakness and fatigue, as well as difficulty with eye movements. Fundoscopic examination revealed pigmentary retinopathy.
A cardiac evaluation uncovered conduction abnormalities, and genetic testing confirmed a mitochondrial DNA deletion, leading to a diagnosis of Kearns-Sayre Syndrome (KSS) with associated ptosis.
The patient was managed with symptomatic treatment, including ptosis crutches and cardiac monitoring, and was counseled on the progressive nature of his condition.
Disease Entity
Kearns-Sayre Syndrome (KSS) is a rare mitochondrial disorder characterized by a triad of:
- Progressive External Ophthalmoplegia (PEO)
- Pigmentary Retinopathy
- Onset before 20 years of age
Ptosis, a hallmark feature of the disease, results from progressive dysfunction of the extraocular muscles due to mitochondrial DNA deletions.
The condition often affects multiple organ systems, making early diagnosis and monitoring crucial.
Pathophysiology
KSS is a mitochondrial disorder caused by deletions in mitochondrial DNA (mtDNA), leading to impaired oxidative phosphorylation.
This results in energy deficits, particularly in high-energy-demand tissues such as:
- Extraocular Muscles: Leading to progressive ophthalmoplegia and ptosis.
- Retina: Causing pigmentary retinopathy.
- Cardiac Tissue: Resulting in conduction abnormalities.
- Skeletal Muscle: Causing generalized weakness.
Ptosis in KSS is primarily due to myopathic involvement of the levator palpebrae superioris rather than a neurological defect.
Epidemiology
- Age of Onset: Symptoms typically appear before 20 years of age.
- Prevalence: Rare; estimated at 1 in 100,000 individuals.
- Sex: No significant gender predilection.
Clinical Features
Ocular Findings
- Bilateral Ptosis: Usually progressive and severe.
- Progressive External Ophthalmoplegia (PEO): Limited ocular motility with sparing of pupillary function.
- Pigmentary Retinopathy: Similar to retinitis pigmentosa, presenting with a “salt-and-pepper” fundus appearance.
Systemic Findings
- Cardiac Conduction Defects: Increased risk of heart block and sudden cardiac death.
- Muscle Weakness: Proximal muscle involvement leads to fatigue.
- Endocrine Abnormalities: Including diabetes mellitus and growth hormone deficiency.
- Neurological Symptoms: Ataxia, hearing loss, and cognitive impairment in some cases.
Diagnostic Evaluation
Ophthalmic Assessment
- Slit-lamp Examination: To assess ptosis severity.
- Fundus Examination: Detects pigmentary retinopathy.
Systemic Testing
- Electrocardiogram (ECG): Essential for detecting conduction defects.
- Serum Lactate and Pyruvate: Elevated due to mitochondrial dysfunction.
- Muscle Biopsy: Shows ragged-red fibers indicative of mitochondrial disease.
- Genetic Testing: Identifies mtDNA deletions.
Differential Diagnosis
- Myasthenia Gravis: Fluctuating ptosis with positive response to acetylcholinesterase inhibitors.
- Chronic Progressive External Ophthalmoplegia (CPEO): Similar to KSS but lacks systemic involvement.
- Oculopharyngeal Muscular Dystrophy: Later onset with dysphagia.
- Congenital Ptosis: Static rather than progressive.
Management
Ocular Treatment
- Ptosis Crutches: Non-surgical option to assist eyelid elevation.
- Surgical Ptosis Repair: Considered in severe cases but may be ineffective due to weak levator function.
Systemic Treatment
- Cardiac Pacemaker: Recommended for those with conduction abnormalities.
- Coenzyme Q10 and Riboflavin: Mitochondrial support therapy with limited evidence.
- Physiotherapy: Helps maintain muscle strength.
Prognosis
- Progressive Nature: Symptoms worsen over time, but life expectancy depends largely on cardiac complications.
- Regular Monitoring: Essential for early intervention, especially for cardiac issues.
Conclusion
Kearns-Sayre Ptosis is a defining feature of Kearns-Sayre Syndrome, a mitochondrial disorder affecting multiple organ systems.
Early diagnosis and multidisciplinary management are critical to improving quality of life.
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References
- DiMauro S, Hirano M. Pathogenesis and treatment of Kearns-Sayre syndrome and CPEO. Neuromuscul Disord. 2006;16(5):195-202.
- Zeviani M, Muntoni F, Savarese G. Mitochondrial diseases: Molecular pathogenesis and therapeutic strategies. Brain. 2022;145(2):523-540.
- Tsao JW, Mendell JR. Mitochondrial disorders presenting with ptosis and ophthalmoplegia. Semin Neurol. 2002;22(1):33-41.
- Finsterer J. Mitochondrial disorders: Neurologic, cardiac, and ophthalmologic manifestations. Acta Neurol Scand. 2019;139(6):477-488.
