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External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 4

External Ophthalmoplegia, Progressive, with mtDNA Deletions, AR 4

Patient Information

Characteristics

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, but there are usually associated neurologic manifestations.  The type described here is largely limited to the eye.

Clinical Correlations

The onset of signs and symptoms usually begin among individuals in the 6th and 7th decades of life. These consist of droopiness of the eyelids and difficulty moving the eyes fully.  However, there is a great deal of variability in all signs and symptoms.  Most manifestations are progressive and include some weakness of arms, legs and shoulders.  Standing from a squatting position is difficult as is climbing stairs.  Speech can be slurred and swallowing difficulties may be evident.  Some patients complain of hearing impairment and more extensive investigations have revealed brain and liver abnormalities.

Genetics

Inheritance

This is an autosomal recessive condition stemming from a change (mutation) in both members of a pair of genes.  Parents carry a mutation in one member of the pair and together they have a 25% chance that each of their children will inherit both changed members of the pair.  Thus the risk of this condition is 25% in all of their children.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

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Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Diagnosis and Prognosis

An ophthalmologist is likely the physician to diagnose this condition.  A full neurological examination is necessary to rule out other neurologic disorders.

There is no treatment for the full condition but surgery can correct the droopy eyelids.  Reported patients have live to old age.

Another highly similar condition in this database is External Ophthalmoplegia, Progressive, With mtDNA Deletions, AR 3.

Web Resources

Web Resource Printout Display
http://en.wikipedia.org/wiki/Chronic_progressive_external_ophthalmoplegia

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