What Is Pachyonychia Congenita?

Working Towards a Differential Diagnosis

There are many rare genetic skin disorders. Clinical diagnosis is often difficult because of similar or overlapping characteristics. For this reason PC Project provides free genetic testing through the PC patient registry (IPCRR).

Although some individuals with PC have been reported to have the following features, data collected on nearly 500 patients with genetically confirmed PC, indicate these are not part of the PC syndrome.

  • Baldness (alopecia)—not caused by or connected with Pachyonychia Congenita

  • Deafness—not caused by or connected with Pachyonychia Congenita

  • Diabetes—not caused by or connected with Pachyonychia Congenita

  • Mental Retardation—not caused by or connected with Pachyonychia Congenita

  • Bone deformities—not caused by or connected with Pachyonychia Congenita

  • Cataracts and corneal lesions—not caused by or connected with Pachyonychia Congenita

  • Early menstrual cycle—not caused by or connected with Pachyonychia Congenita

The IPCRR Status Chart includes a listing of the many other disorders referred to the IPCRR for testing.

 

 

Pachyonychia Congenita (PC) is an ultra-rare genetic autosomal dominant skin disorder. PC is caused by a mutation in one of five keratin genes including K6a, K6b, K6c, K16, or K17.

Keratin genes are responsible for production of keratins, which are tough, fibrous proteins that form filaments to support skin cells and give them shape and strength. Keratin filaments help cells handle pressure and stretching. With PC, the filaments do not form properly, causing extreme cell fragility.

The specific gene and specific mutation involved affects the disease condition for the PC patient. These different types of PC are properly classified as PC-K6a, PC-K6b, PC-K6c, PC-K16 and PC-K17 (related to the affected keratin gene where the mutation is located.)

This disorder does not affect lifespan, but almost all patients experience constant pain. 

For explanations of the terms used to describe Pachyonychia Congenita, see the Glossary.

The most common features of PC include:

  1. Thickened Nails (hypertrophic nail dystrophy or pachy-onychia) although not all nails are affected in all patients with PC. 
  2. Painful calluses and blisters on the soles of the feet (focal plantar hyperkeratosis). Pain is one of the distinct characteristics of PC. Blisters are found under the callus in PC patients. Calluses may also form on the palms of the hands (palmar hyperkeratosis).
  3. Cysts of various types (including steatocystoma and pilosebaceous cysts). In some forms of PC, this is the most dominant, painful and problematic characteristic.
  4. Follicular hyperkeratosis (FHK or bumps around hairs at friction sites such as waist, hips, knees, elbows). Most common in children and lessens after teenage years.
  5. Leukokeratosis of the oral mucosa (white film on tongue and inside cheeks). This is not painful, but is often misdiagnosed as thrush or as leukoplakia.

Less common features of PC include:

  1. Sores at the corner of the mouth (angular cheilitis).
  2. Teeth at or before birth (natal or pre-natal teeth). This is found in one subset of PC.
  3. Laryngeal involvement with a white keratin film on the larynx. This results in a hoarse cry or a hoarse voice and is found in only a few patients.
  4. Intense pain on first bite (‘first bite syndrome’). The pain is near the jaw or ears and lasts 15–25 seconds when beginning to eat or swallow. This is more common in younger children and is often confused with ear problems.  

PACHYONYCHIA CONGENITA (PC) or ?

When publishing articles on PC, we urge editors and authors to rely on data based on genetically confirmed patients and on case series of patients rather than single cases (single families) with no genetic testing. It may also be valuable to compare the information with the data in the IPCRR. Articles based solely on clinical observation without genetic information may incorrectly identify conditions as 'pachyonychia congenita'. Also, because PC is an ultra rare skin disorder, publications based on a single case or single family may include features of the family that are not actually associated with PC. Once published, the information in these articles may then be cited in other articles. In this way, conditions have become linked with PC which are totally unrelated to this disorder.

Websites may also have information that is confusing, misleading or incorrect. For example, since the word ‘Pachyonychia’ means ‘thick’ (pachy) ‘nails’ (onychia), a search for the word Pachyonychia on the internet will return sites which list all disorders that have thickened nails. This is not an indication that the conditions associated with thickened nails are associated with the disorder Pachyonychia Congenita. Thick nails (pachyonychia) can have many causes that have no relationship to PC.

One goal of PC Project is our educational outreach effort to provide editors, authors, physicians, patients and family members with accurate information based on a large number of genetically confirmed patients in order to assist in diagnosis, treatment and research efforts.