External Ophthalmoplegia, POLG and mtDNA Mutations

Background and History: 

This disorder of eye movement was first described by an ophthalmologist, Albrecht Von Graefe, in 1868.  A number of genetic disorders cause difficulties in eye movement, known as external ophthalmoplegia.  Some of these conditions, such as the one described here, also cause systemic muscle and neurological problems.

Clinical Correlations: 

An early sign of this disorder is difficulty in opening the eyes completely because the upper eyelids droop, a condition known as ptosis.  Patients often compensate by raising their chin.  Exercise tolerance is reduced at about the same time.  Some patients have difficulty swallowing, while speech may be slurred.  Adults may experience unsteadiness, depression, difficulties in the sense of touch and pain, and may develop tremors and other signs of parkinsonism.  Some hearing loss is often present.  Cataracts can develop at a young age.


This is a complex disorder and probably consists of several types.  Classification is difficult for not only is there a mutation in the DNA of chromosome 15, but there are abnormalities in the DNA of the mitochondria, the energy powerhouses of cells.  Some family trees are consistent with autosomal dominant inheritance (due to a single mutation passed from parent to child), while others resemble autosomal recessive patterns where two mutations, one from each normal parent, are inherited.

Diagnosis and Prognosis: 

Ophthalmologists and neurologists are usually able to make the diagnosis.  The prognosis is highly variable and the course of disease therefore is difficult to predict.  Some handicap from the muscle disease is common.

There is no treatment for the eye movement problems but the droopy eyelids can be elevated surgically.

Additional Information
Autosomal dominant
Autosomal recessive