Rare Gastroenterology News

Disease Profile

Pachyonychia congenita

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

ageofonset-all.svg

ICD-10

Q84.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Congenital pachyonychia; Pachyonychia congenita syndrome

Categories

Congenital and Genetic Diseases; Skin Diseases

Summary

Pachyonychia congenita (PC) is a rare inherited condition that primarily affects the nails and skin. The fingernails and toenails may be thickened and abnormally shaped. Affected people can also develop painful calluses and blisters on the soles of their feet and less frequently on the palms of their hands (palmoplantar keratoderma). Additional features include white patches on the tongue and inside of the mouth (leukokeratosis); bumps around the elbows, knees, and waistline (follicular hyperkeratosis); and cysts of various types including steatocystoma. Features may vary among affected people depending on their specific mutation.[1][2] PC is divided into 5 types based on the specific keratin gene involved: PCK6a, PCK6b, PCK6c, PCK16, and PCK17. All forms are inherited in an autosomal dominant manner.[2][3] Treatment is based on the signs and symptoms present in each person.[2]

Symptoms

The signs and symptoms of pachyonychia congenita (PC) vary based on the specific keratin gene involved (KRT6A, KRT6B, KRT6C, KRT16, and KRT17) and the specific gene mutation. However, the most common features of the condition include:[3][2]

  • Thickened nails
  • Plantar hyperkeratosis (thickened skin on the soles of the feet) with underlying blisters
  • Plantar pain
  • Various types of cysts (i.e. steatocystoma and pilosebaceous cysts two types of sebaceous gland cysts)
  • Follicular hyperkeratosis (small bumps at the base of hairs)
  • Leukokeratosis (white patches on the tongue, in the mouth, or on the inside of the cheek)

Some affected people may also develop calluses on the palms of the hands (palmar hyperkeratosis), sores at the corner of the mouth; natal teeth; a hoarse cry or voice caused by white film on the larynx (voice box); and/or intense pain when beginning to eat or swallow.[3][2]

For more specific information on the signs and symptoms of PC, including specific features that are not associated with the condition, please visit the Pachyonychia Congenita Project's website.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Hyperplastic callus formation
0030268
Lower limb pain
Leg pain
0012514
Onychogryposis of toenails
Overgrowth and curving of toenails
0008401
Palmoplantar blistering
0007446
30%-79% of people have these symptoms
Fingernail dysplasia
Abnormal fingernail development
0100798
Follicular hyperkeratosis
0007502
Linear arrays of macular hyperkeratoses in flexural areas
0007490
Onychogryposis of fingernail
Overgrowth and curving of fingernail
0040036
Palmar hyperkeratosis
0010765
Palmoplantar hyperhidrosis
Excessive sweating of palms and soles
0007410
5%-29% of people have these symptoms
Ear pain
Pain in the ear
0030766
Eruptive vellus hair cyst
0025248
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Natal tooth
Born with teeth
Teeth present at birth

[ more ]

0000695
Paronychia
0001818
1%-4% of people have these symptoms
Alopecia
Hair loss
0001596
Angular cheilitis
Inflammation of corners of the mouth
Red and sore corners of the mouth

[ more ]

0030318
Hoarse voice
Hoarseness
Husky voice

[ more ]

0001609
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Chapped lip
Chapped lips
Dry lips

[ more ]

0040181
Dry hair
0011359
Epidermoid cyst
Skin cyst
0200040
Folliculitis
0025084
Furrowed tongue
Grooved tongue
0000221
Gingivitis
Inflamed gums
Red and swollen gums

[ more ]

0000230
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Nail dysplasia
Atypical nail growth
0002164
Nail dystrophy
Poor nail formation
0008404
Onychogryposis
Thick nail
Thickened nails

[ more ]

0001805
Oral leukoplakia
Oral white patch
0002745
Palmoplantar hyperkeratosis
Thickening of the outer layer of the skin of the palms and soles
0000972
Palmoplantar keratoderma
Thickening of palms and soles
0000982
Plantar hyperkeratosis
0007556
Sparse and thin eyebrow
Thin, sparse eyebrows
0000535
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

0002209
Steatocystoma multiplex
0012035
Subungual hyperkeratosis
Thickened, discolored skin under nail
0008392

Cause

Pachyonychia congenita (PC) is caused by changes (mutations) in one of five genes: KRT6A, KRT6B, KRT6C, KRT16, and KRT17. These genes provide instructions for making a protein called keratin, which is found in the skin, hair, and nails. Mutations in any of these genes alter the structure of keratin proteins which interferes with their ability to provide strength and resilience to various parts of the body. This leads to the many signs and symptoms associated with pachyonychia congenita.[1]

PC is divided into 5 types based on the specific keratin gene involved: PC-K6a, PC-K6b, PC-K6c, PC-K16, and PC-K17.[3]

Diagnosis

A diagnosis of pachyonychia congenita (PC) is often suspected based on the presence of characteristic signs and symptoms. In fact, one study found that approximately 97% of people with genetically confirmed PC have toenail thickening, plantar keratoderma (thickening of the skin on the soles of the feet) and plantar pain by age ten.[2][3]

Identification of a change (mutation) in one of the five genes associated with PC confirms the diagnosis. [2][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Current management of pachyonychia congenita is focused on relief of pain and other symptoms; hygienic grooming practices (such as trimming the nails and calluses); and treatment of infections when necessary. Some people may also require aids to help with mobility, such as wheelchairs, crutches and/or canes.[2][5]

    Pachyonychia Congenita Project offers more detailed information regarding the treatment and management of PC. Please click on the link to access this resource.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • MedlinePlus Genetics contains information on Pachyonychia congenita. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          Pachyonychia congenita 1
          Pachyonychia congenita 2
          Pachyonychia congenita 3
          Pachyonychia congenita 4
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Pachyonychia congenita. Click on the link to view a sample search on this topic.

          References

          1. Pachyonychia congenita. Genetics Home Reference. August 2012; https://ghr.nlm.nih.gov/condition/pachyonychia-congenita.
          2. Frances JD Smith, PhD, C David Hansen, MD, Peter R Hull, MD, PhD, FRCPC, Roger L Kaspar, PhD, Mary E Schwartz, LLD, WH Irwin McLean, DSc, FRSE, Leonard M Milstone, MD, Maurice van Steensel, MD, PhD, Edel O’Toole, MD, PhD, FRCPI, FRCP, and Eli Sprecher, MD, PhD. Pachyonychia Congenita. GeneReviews. July 2014; https://www.ncbi.nlm.nih.gov/books/NBK1280/.
          3. What is Pachyonychia Congenita?. Pachyonychia Congenita Project. https://www.pachyonychia.org/what-is-pc/. Accessed 12/10/2015.
          4. Newly Diagnosed With PC. Pachyonychia Congenita Project. https://www.pachyonychia.org/newly-diagnosed-with-pc/. Accessed 12/10/2015.
          5. Goldberg I1, Fruchter D, Meilick A, Schwartz ME, Sprecher E. Best treatment practices for pachyonychia congenita. J Eur Acad Dermatol Venereol. March 2014; 28(3):279-285. https://www.ncbi.nlm.nih.gov/pubmed/23363249.
          6. George SJ & Elston DM. Pachyonychia Congenita. Medscape Reference. March 2014; https://emedicine.medscape.com/article/1106169-overview#a4.

          Rare Gastroenterology News