Pachyonychia congenita is a painful and crippling disorder with an autosomal dominant inheritance presented at childhood. It is characterized by hyperkeratinization of various sites due to mutated genes responsible for keratin synthesis.
Pachyonychia congenita (PC) is clinically seen with several distinctive features comprising a diagnostic triad of :
Although these components are most common, elements of the triad may be absent in some patients, making it an optional diagnostic instrument. As PC is associated with mutations in keratin genes, the affected areas are located in places abundant in keratinization, particularly, soles of the feet. PC in such location gives rise to painful and crippling lesions of keratoderma linked with repetitive blistering in the callus . The pain is related to secondary infections, pressures in the nerve endings and blister fluid accumulation under the epidermis of callus .
Dystrophic nails can vary in appearance between family members thought to carry the same mutation. The nails usually appear hypertrophied, discolored with atypical angulation on the nail bed. The presence of these abnormalities can be spared in some nails, affecting only the specific ones, most commonly on the toes .
Those afflicted with PC also present with cystic processes in the epidermis like follicular keratosis or pilosebaceous cyst formation . These can be located over the entire body although most typical sites are the neck, face, back, abdomen, and buttocks . A classification of PC in two types (PC-1 and PC-2) was dependent on the presence of these pilosebaceous cysts and other features but in time could not survive criticism . Thus a new classification based on the mutant gene came into existence. Modern grouping contains four subclasses of PC, which are PC-6a, PC-6b, PC-16, and PC-17 each based on mutations encoding K6a (for the PC-6a subtype accordingly) or other proteins .
Diffuse hair loss or alopecia can accompany PC .
Entire Body System
- Nail Abnormality
Pachyonychia congenita type I is an autosomal dominant disorder where nail abnormalities are a constant feature and develop during childhood. [ncbi.nlm.nih.gov]
We studied three families suffering from nail abnormalities who had previously been diagnosed as pachyonychia congenita. No keratin gene mutations were detected. [rug.nl]
Children with nail abnormalities may find classmates avoiding them in games which require holding hands or touching. [socialstyrelsen.se]
- Heterochromia Iridis
We report an infant who had clinical features consistent with pachyonychia congenita type II, with unusual features of microcephaly, seizures, electroencephalogram abnormalities, failure to thrive, and heterochromia iridis. [ncbi.nlm.nih.gov]
We present an individual who had different nail dystrophy, epidermal cysts, mental retardation, blepharitis, complete loss of teeth, and negative keratin gene mutations for pachyonychia congenita and developed squamous cell cancer on the oral leukokeratosis [ncbi.nlm.nih.gov]
[…] genotypically to the specific mutations in patients with pachyonychia congenita. [emedicine.com]
Pachyonychia congenita Pachyonychia congenita has an autosomal dominant pattern of inheritance. [en.wikipedia.org]
CONGENITA, JADASSOHN-LEWANDOWSKY TYPE Pachyonychia Congenita Type 1 edit English pachyonychia congenita rare group of autosomal dominant skin disorders that are caused by a mutation in one of five different keratin genes Jackson-Lawler Type Pachyonychia [wikidata.org]
Rittié, Pachyonychia congenita cornered: report on the 11th Annual International Pachyonychia Congenita Consortium Meeting, British Journal of Dermatology, 171, 5, (974-977), (2014). F. Abdollahimajd, F. Rajabi, M. Shahidi‐Dadras, S. Saket, L. [doi.org]
- Nail Deformity
This type of subungual hyperkeratosis leads to the elevation and increased transverse curvature of the nail plate.  The elevation is most pronounced distally resulting in an omega or pincer nail deformity. [ijpd.in]
The elevation is most pronounced distally, sometimes resulting in a pincer nail deformity. [jiaomr.in]
Typical nail changes of pachyonychia congenita: yellow-gray discoloration and thickening of nail plates, subungual hyperkeratosis, upward angulation of the nail and pincer nail deformity Examination revealed thickening and hardening with yellow-grey discoloration [escholarship.org]
The elevation is most pronounced distally resulting in an omega or pincer nail deformity. The nail plates are also discolored, thick, and friable, and they sometimes fail to reach the distal fingertip. [ijhas.in]
A biopsy can be taken from a hyperkeratotic area and observed in a light microscope where acanthosis and orthokeratosis may be seen. Immunohistochemistry with the addition of antibodies can be useful  .
Genetic studies are performed with an objective to educate the patient about the specifics of PC and to collect data for research in order to find the best treatment for a particular mutation . These exams involve the amplification of affected genes utilizing a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Mutations in four types of genes responsible for the synthesis of K6a, K6b, K16, and K17 proteins are noted .
Some examinations radiologic like ultrasonography (US) can be useful to follow the dynamics of the disease. High-resolution US can be applied to examine the affected calluses for the fluid in blisters, thrombosis, and underlying vein lesions. Hyperkeratinization is characterized by hyperechoic linear and dotted areas. Fluid will be seen as anechoic and situated under the epidermis .
RESULTS: Patients reported surgical treatments being most effective for cysts and mechanical treatments the most effective conventional therapeutic approach for all other investigated manifestations. [ncbi.nlm.nih.gov]
Results Patients reported surgical treatments being most effective for cysts and mechanical treatments the most effective conventional therapeutic approach for all other investigated manifestations. [doi.org]
Knowledge of the exact gene defect is likely to assist in predicting disease prognosis and clinical management. [ncbi.nlm.nih.gov]
Prognosis - Pachyonychia Congenita Not supplied. Treatment - Pachyonychia Congenita Not supplied. Resources - Pachyonychia Congenita Not supplied. [checkorphan.org]
Prognosis Complications may include secondary infection that is usually well controlled by antibiotics therapy. [orpha.net]
Last updated: 12/10/2015 The long-term outlook (prognosis ) for people with pachyonychia congenita (PC) varies. Although the condition is not associated with a reduced lifespan, it can negatively impact quality of life. [rarediseases.info.nih.gov]
Etiology Although historically two subtypes have been described, PC-1 and PC2, it is today recommended to classify PC patients into four subgroups based the underlying molecular etiology: PC-K6a, PC-K6b, PC-K16 and PC-K17, as PC is caused by dominant [orpha.net]
Some authors propose that steatocystoma multiplex is simply a variant of pachyonychia congenita type 2 because they both share the same underlying etiology. [diki.pl]
GENETIC CAUSES OF PACHYONYCHIA CONGENITA Etiology & Pathogenesis 1/31/2015 Prepared by Dixi Dawn F. Apigo 10. [slideshare.net]
Etiology Genetic: Keratins 6a, 6b, 16, and 17. Keratin 6c may produce an attenuated phenotype known as hereditary painful callosities. Pathogenic mutation in one of the above keratins compromises appropriate filament formation. [dermatologyadvisor.com]
Summary Epidemiology The prevalence is not known but approximately 1000 patients have been registered to date worldwide. Clinical description PC presents clinically as a spectrum of conditions. [orpha.net]
Any secondary infection may need to be treated with antibiotics, though infection can often be prevented with appropriate grooming and vinegar or bleach baths. Epidemiology Pachyonychia congenita is a rare disorder with an unknown prevalence [en.wikipedia.org]
Epidemiology Frequency Although the exact frequency of pachyonychia congenita is unknown, it appears to be rare. [emedicine.com]
[…] few months of life.   :569 Signs and symptoms Common symptoms include: Excess keratin in nail beds and thickening of the nails Hyperkeratosis on hands and feet Oral lesions that look like thick white plaques Steatocystoma multiplex Pain Blisters Pathophysiology [ipfs.io]
Pathophysiology The condition is caused by genetic mutations in one of four genes that encode keratin proteins specific to the epithelial tissues affected in the two forms of the disorder. [wikidoc.org]
Pathophysiology Keratins are key structural proteins that form the cytoskeleton of epithelial cells. They are classified based on their biochemical properties into either type I (K9-K28, K31-K40) or type II keratins (K1-K8, K71-K86). [emedicine.com]
Pathophysiology Mutated keratin filaments aggregate, resulting in weakened filament structures and consequent cellular fragility. [dermatologyadvisor.com]
Efforts to decrease skin friction and moisture may also improve and/or prevent transgrediens spread. [ncbi.nlm.nih.gov]
Prevention - Pachyonychia Congenita Not supplied. [checkorphan.org]
Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [simplygoodnaturalfoods.com]
Topical application of the NRF2 activator sulforaphane to the footpad of Krt16 –/– mice prevented the development of PPK and normalized redox balance via regeneration of GSH from existing cellular pools. [jci.org]
- Van Steensel MAM, Coulombe PA, Kaspar RL, et al. Report of the tenth annual International Pachyonychia Congenita Consortium meeting. J Invest Dermatol. 2014;134(3):588-591.
- WHI McLean, CD Hansen, MJ Eliason, FJD Smith.The Phenotypic and Molecular Genetic Features of Pachyonychia Congenita. J Invest Dermatol. May 2011;131(5):1015–1017.
- Cao Y-A, Hickerson RP, Seegmiller BL, et al. Gene Expression Profiling in Pachyonychia Congenita Skin. J Dermatol Sci. 2015;77(3):156-165.
- Rathore PK, Khullar V, Das A. Pachyonychia Congenita Type 1: Case Report and Review of the Literature. Indian J Dermatol. 2016;61(2):196-199.
- Wilson NJ, Leachman SA, Hansen CD. A large mutational study in pachyonychia congenita. J Invest Dermatol. 2011 May;131(5):1018-24.
- Nikoo A. Pachyonychia Congenita-Associated Alopecia. Case Rep Pathol. 2012:850658.
- Rathore PK, Khullar V, Das A. Pachyonychia Congenita Type 1: Case Report and Review of the Literature. Indian Journal of Dermatology. 2016;61(2):196-199.
- Wilson N, O’Toole E, Milstone L, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014;171(2):343-355.