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Pfeiffer Syndrome

Pfeiffer Syndrome

Patient Information

Characteristics

Background and History

This disorder is caused by several mutations that cause severe skull and skeletal deformities.  Mutations in the same gene cause other syndromes such as Crouzon, Apert, and Jackson-Weiss with many overlapping features.  

Clinical Correlations

The skull is malformed in a manner that shortens the eye socket and the cheek area of the face is not fully formed.  As a result, the eyes are often prominent and this can interfere with effective blinking which can lead to dry eyes.  The distance between the eyes is often greater than normal.  In a few cases there are other eye problems such as underdevelopment of the optic nerve that connects the eye to the brain.

Hearing loss is common.  The thumbs and great toes are large and broad and in some cases the elbows have limited mobility.  Malformations in the airways can lead to severe respiratory problems.

Genetics

Inheritance

This is an autosomal dominant disorder with a vertical pattern of inheritance.  Affected parents can pass the single mutation directly to their offspring.  However, many are only mildly affected which sometimes suggests that a new mutation is responsible.  Of course, new mutations can and do occur with a higher risk for this in older men.

Mutations in at least 2 genes have been found in this syndrome.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

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Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Diagnosis and Prognosis

The diagnosis often requires a team approach consisting of medical geneticists, ophthalmologists, and orthopedists.  Pfeiffer syndrome has been subdivided into at least 3 types, and generally only type 1 is compatible with life to adulthood.  The prognosis is good for such individuals.  However, an eye doctor should be consulted to ensure that dry eyes are adequately treated.  Severe underdevelopment of the midface can sometimes be surgically corrected.  Airway obstruction may require surgical intervention.

Web Resources

Web Resource Printout Display
http://ghr.nlm.nih.gov/condition/pfeiffer-syndrome

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