Variation in the PC syndrome
Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, 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 four genes and across the numerous mutations, the unbearable and debilitating pain is a main characteristic of the four types PC-K6a, PC-K6b, PC-K16 and PC-K17.
PC-K6a and PC-K16 patients appear to experience the greatest degree of plantar pain, with PC-K6b 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 and of a slightly different type.
Nail changes are extreme in PC-K6a and PC-K16 (except for specific PC-K16 mutations which do not affect fingernails). PC-K6b and PC-K17 usually have milder nail changes. Again, there are variations and exceptions across each of the four types.
Because PC-K6c is so mild with limited nail changes, it is unclear whether it should be included in the Pachyonychia Congenita syndrome.
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.
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 where PC patients are located (now in nearly 60 countries).
Do changes in KRT6c cause Pachyonychia Congenita? While it is established that KRT6c causes PPK, there is still a question as to whether changes in KRT6c should be classified as Pachyonychia Congenita especially because the condition presents only tender feet and not the disabling pain that is the most typical feature for those with PC. Professor Paul Bowden outlines the challenge "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 and other articles about K6c see the Research Articles section of this website.
Recent publications have included PC-K6c as a type of pachyonychia congenita. However, as additional families are studied and as these changes may be found in the general population, this classification may be modified. Certainly PC-K6c is a much milder form than any of the other four types.