Kearns-Sayre Syndrome

1. Kearns-Sayre Syndrome Charles Shepherd Bio 313

2. Background • Rare neuromuscular disorder • Only 226 cases reported in literature • Effects mitochondria • Large duplications or deletions in mitochondrial DNA (>1000bp) results in under or over production of mitochondrial gene products • 1/3 cases 4977bp deletion • Randomly effects people • only isolated reports of any kind or inheritance pattern • Prognosis • Depends on severity • Severe cases 85% muscle mitochondrial genome affected

3. Symptoms • Onset before 20 and includes • Immobile or limited eye movement • Abnormal pigment in eyes • Cardiac problems or congestive heart failure • Muscle and skeletal weakness • Short stature • Hearing • Ataxia (coordination problems) • Diabetes • Dementia and other mental illnesses • Affects systems with higher energy requirements most

4. Diagnosis • Southern Blots using samples taken from affected tissue • Isolate mitochondrial DNA from affected tissue • 16.5 kb = normal • Additional larger or smaller bands found by probes = duplication or deletion • Accumulation of symptoms • Check the protein and lactate levels in the cerebrospinal fluid • if present, the levels are elevated.

5. Treatment • Supportive • Syndrome becomes worse with time • inevitably fatal • Symptomatic • Heart • Muscle • Hearing • Diabetes • Vision • Drugs

6. Noticed Anomalies in lab studies • Changes in grey and white matter levels in various parts of the brain • Many help explain dementia seen in some individuals • Abnormally large irregularly shaped mitochondria in heart and skeletal muscle

7. References • http://www.ninds.nih.gov/disorders/kearns_sayre/kearns_sayre.htm • http://www.emedicine.com/ped/topic2763.htm • Pasternak, J. J. An Introduction to Human Molecular Genetics: Mechanisms of Inherited Diseases. 2nd ed. New Jersey: Wisley, 2005.