Variation in the PC syndrome
Dominant-negative mutations in any of the five identified keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17, cause pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and other ectodermal features. While there is a variety of patterns of keratoderma across the different genes and across the numerous mutations, the unbearable and debilitating pain is a main characteristic of all types PC-K6a, PC-K6b, PC-K6c, PC-K16 and PC-K17.
PC-K6a and PC-K16 patients appear to experience the greatest degree of plantar pain, with PC-K6b, PC-K6c and PC-K17 somewhat less plantar pain.
PC-K17 patients have hundreds of cysts which also cause intense pain at times. Those with PC-K6a also have cysts although not nearly as numerous as PC-K17.
A pain study and Quality of Life review conducted in 2011 showed PC-K17, PC-K6a, PC-K16, PC-K6b worst to best. Although no PC-K6c patients were tested at that time, we assume those patients would test in a similar way to PC-K6b.
Nail changes are extreme in PC-K6a and PC-K16 (except for specific PC-K16 mutations which do not affect fingernails). PC-K6b, PC-K6c and PC-K17 usually have milder nail changes. Again, there are variations and exceptions across each of the types.
For all types of PC, pain is the most delibitating factor. While some social issues affect those with PC during childhood and teenage years, the thing all PC patients hope for is relief from pain.
The IPCRR patient registry collects data on PC which guides research and treatment development
PC Images show the variations in the PC syndrome
Status Chart see which PC mutations are most common (and the list of other disorders diagnosed as PC).
Mutations Chart see the nearly 100 specific mutations now found in the five PC genes.
Mutations Schematic Chart shows the location of mutations along each of the five PC genes.
IPCRR Summary Data see how the various types of PC compare with this overview of IPCRR data.
IPCRR Growth Count see how the IPCRR has grown over the years.
Location Chart see pdf of where patients in the IPCRR with confirmed PC are located (now in nearly 40 countries).
Map of PC Patients see a interactive map of where genetically confirmed PC patients in the IPCRR are located.
Do changes in KRT6c cause Pachyonychia Congenita? While it is established that KRT6c causes PPK, for a time there was a question as to whether changes in KRT6c should be classified as Pachyonychia Congenita. Now that there are additional cases in the IPCRR registry, KRT6c has been accepted as PC-K6c. Publications since 2011 by those active in the International PC Consortium now consistently include KRT6c mutations as one of the types of PC. (See publications featured in the Published Research Articles sidebar.)
In 2010, Professor Bowden outlined the challenge that existed regarding whether changes in KRT6c should be classified as Pachyonychia Congenita. "Twenty years have elapsed since keratin mutations were linked to cutaneous genodermatoses, and we now know that they cause 40 different genetic disorders. (Researchers) have identified KRT6Cmutations in patients with focal palmoplantar keratoderma (FPPK), but debate concerning overlapping phenotypes between FPPK and pachyonychia congenita (PC) will continue because only one family has nail involvement. Furthermore, screening of control DNA samples identified 3 in 335 individuals (1%) who had a mutation (K6c p.Asn172del), but the phenotype was not ascertained. However, this raises the question as to whether individuals with sensitive feet bear specific KRT6C mutations and whether a general population screen should be considered." Bowden, Paul Edward 2010. Mutations in a keratin 6 isomer (K6c) cause a type of focal palmoplantar keratoderma. Journal of Investigative Dermatology 130 (2) , pp. 336-338. 10.1038/jid.2009.395. For full text of this article see the Published Research Articles on this website.