NORD gratefully acknowledges Noralane M. Lindor, MD, Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, for assistance in the preparation of this report.
Pachydermoperiostosis is a rare disorder characterized by clubbing of the fingers, thickening of the skin of the face (pachyderma), and excessive sweating (hyperhidrosis). It typically appears during childhood or adolescence, often around the time of puberty, and progresses slowly for about ten years.
Specific symptoms include enlargement of the fingers and toes (clubbing), a condition in which there is a fibrous covering on the ends of the long bones (periostosis), coarse facial features, increased bulk of the skin on the scalp forming folds, depressions or furrows of the scalp (cutis verticis gyrata), and/or excessive sweating of the hands and feet. Pachydermoperiostosis is the complete or primary form of a more common disorder known as idiopathic primary hypertrophic osteoarthropathy (HOA).
Patients with pachydermoperiostosis typically have coarse facial features with oily, thick, grooving skin on the face. Joint pain, an abnormal enlargement of the tips of the fingers and toes (clubbing), and excessive sweating of the hands and feet (hyperhidrosis) may also be present.
New fibrous bone growth (periostosis), especially of the ends of the long bones, is present in patients with pachydermoperiostosis. A condition in which the skin of the scalp has excess bulk causing depressions or grooves (cutis verticis gyrata) typically becomes apparent during the teen years.
Other symptoms found in some patients with pachydermoperiostosis may be: swelling or pain of the large joints; drooping eyelids (ptosis); a long-term inflammatory skin disease that causes dry or moist, scales and a yellowish crust (seborrheic dermatitis); disorders such as ulcers; and/or swelling of hair follicles related to large open pores of the skin.
The symptoms in patients with pachydermoperiostosis vary in severity with males typically having a more severe form of the disorder.
For most patients, the diagnosis of pachydermoperiostosis is a clinical diagnosis, recognized more frequently in males than females. Autosomal dominant inheritance has been reported, and for that presentation, no gene mutation has been identified. Some families have autosomal recessive inheritance and recently mutations in gene called 15-hydroxyprostaglandin dehydrogenase have been identified [Uppal et al., 2008]. In individuals with mutations in this gene, urinary prostaglandin E2 levels are elevated, but this test is not readily available. Clinical genetic testing is also not yet available.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Pachydermoperiostosis is a rare disorder that affects males more often than females with a ratio of 7:1. This ratio may not be totally valid since females often have milder symptoms than do men, with the fibrous bone growth (periostosis) not being detected unless X-rays are taken.
Diagnosis is made clinically. Major diagnostic criteria for HOA are clubbing of the fingers (digital clubbing) and fibrous bone growth (periostosis). Pachydermoperiostosis is the complete form of HOA. There are also three incomplete forms. clubbing alone, periostosis without clubbing, and pachyderma.
Treatment is mostly aimed at specific symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids may be administered to reduce bone and joint pain associated with the disorder.
A vagotomy, a surgical procedure in which certain branches of the vagus nerve are cut, may in some instances improve joint pain and swelling. Plastic surgery may be performed to improve facial appearance.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
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FROM THE INTERNET
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