NORD gratefully acknowledges Sunaina Kapur, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Pachydermoperiostosis, also called primary hypertrophic osteoarthropathy (PHO) is a rare genetic condition. The three main features are large finger tips (clubbing), thickening of the skin of the face (pachydermia) and extra sweating (hyperhidrosis). It typically starts during childhood or adolescence, often around the time of puberty, and progresses slowly for about ten years.
Pachydermoperiostosis is the complete form of PHO where there is also unusual thickness of the skin (pacydermia). There are also two incomplete forms, one with isolated bone problems and skin changes, and one with pachydermia and minimal or absent new bone growth (periostosis).
PHO is characterized by problems with the growth of skin and bones. People with PHO usually have coarse facial features with oily, thick, grooved skin on the face, joint pain, large tips of the fingers and toes (clubbing) and extra sweating of the hands and feet (hyperhidrosis).
New bone growth (periostosis), often at the ends of the long bones, causes joint pain. Extra skin on the scalp can be seen that causes deep grooves or ridges (cutis verticis gyrate).These grooves or ridges usually occur during the teen years.
Other symptoms can include swelling or pain of the large joints; drooping eyelids (ptosis); a long-term skin condition that causes dry or moist scales and a yellowish crust (seborrheic dermatitis); ulcers; long eyelashes; occasional diarrhea; swelling of hair follicles related to large open pores of the skin; heart disease present at birth and/or delayed closure of the space between the bones of the skull (fontanelles).
The symptoms vary between individuals, but overall, males tend to have more serious symptoms than females. X-rays can help look at features that are not as noticeable to the naked eye.
For most individuals, the diagnosis of PHO is based on the clinical features. It is recognized more often in males than females, as males have more noticeable and severe features. PHO can be inherited, but a non-genetic form has also been described.
Genetic conditions can be inherited in different ways. Individuals typically inherit one copy of a gene pair from their mother, and the other from their father. Genes provide instructions to tell the body how to function. When there is a harmful change (mutation) in a gene it may not function normally leading to unusual features and/or conditions. Autosomal dominant and autosomal recessive inheritance patterns have been reported for PHO.
There are two genes that have been associated with PHO: HPGD and SLCO2A1. Mutations in HPGD are associated with autosomal recessive inheritance and this condition is sometimes abbreviated PHOAR1 or Touraine-Solente-Gole syndrome.
Recessive genetic conditions occur when an individual inherits one non-working gene for the same condition from each parent. If an individual receives one normal gene and one gene with a mutation, the person will be a carrier for the condition and will usually not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have a child with that condition is 25% with each pregnancy. The chance to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal working genes from both parents is 25%. The chance is the same for males and females.
Parents who are closely related by blood (consanguineous) have a higher chance than unrelated parents to both carry the same non-working gene, which increases the chance to have children with a recessive genetic disorder.
PHO caused by mutations in SLCO2A1 can be dominant or recessive. The recessive form is called PHOAR2. The dominant form is called PHOAD. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to see symptoms of the condition. The non-working gene can be inherited from either parent or can be the result of a new mutation (gene change) in the individual with the condition. The chance of passing the non-working gene from an affected parent to child is 50% for each pregnancy. The risk is the same for males and females. However, with PHOAD, males are more commonly and often more severely affected.
PHO is a rare disorder that affects males more than females with a ratio of 7:1. This means that for about every 7 males that are diagnosed with this condition, 1 female is diagnosed. However, since females tend to have milder symptoms than males, females may go undiagnosed.
The diagnosis of PHO is made based on clinical features, though genetic testing can confirm the diagnosis. Major diagnostic criteria include clubbing of the fingers (digital clubbing) and new bone growth (periostosis).
Treatment is mostly aimed at specific symptoms and is supportive. Nonsteroidal anti-inflammatory drugs (NSAIDs, such as Advil), colchicine, or corticosteroids can be taken to decrease bone and joint pain.
Vagotomy, a surgical procedure in which certain branches of the vagus nerve are cut, may improve joint pain and swelling. Retinoids can be used to treat symptoms that involve the skin. Plastic surgery may be performed to improve facial appearance. Surgery can treat clubbing of the fingers.
Genetic counseling may be helpful for patients and their families.
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