K6b-pEDD-PC

Patients with mutations in PC-K6b have a milder form of PC, but experience painful plantar keratoderma as the most challenging feature.

ABOUT THE KRT6B GENE

The KRT6B gene provides instructions for making a protein called keratin 6b or K6b. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, nails, and similar tissues.  Keratin 6b is produced in the nails, the hair follicles, and the skin on the palms of the hands and soles of the feet. It is also found in the skin’s sebaceous glands, which produce an oily substance called sebum.

Keratin 6b partners with a similar protein, keratin 17, to form molecules called keratin intermediate filaments. These filaments assemble into dense networks that provide strength and resiliency to the skin, nails, and other tissues. Networks of keratin filaments protect these tissues from being damaged by friction and other everyday physical stresses. Keratin 6b is also among several keratins involved in wound healing

The KRT6B mutations responsible for PC-K6b¹ change the structure of keratin 6b, preventing it from working effectively with keratin 17 and interfering with the assembly of the keratin intermediate filament network. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of painful blisters and calluses. In the sebaceous glands, abnormal keratin filaments lead to the development of cysts called steatocystomas.  Defective keratin 6b also disrupts the growth and function of cells in the nails and hair follicles, which explains why the signs and symptoms of PC-2 also affect these tissues. (Adapted from http://ghr.nlm.nih.gov/gene/KRT6B.)

¹PC classification replacing PC-1 and PC-2 classification. See W. H. McLean et al. The
phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol. 2011;131(5):1015-7.

To learn how many others have mutations in the same gene and the same mutation, visit the PC data page where there is detailed information on those with PC and the various mutations.

Observations on PC-K6b from the IPCRR

Patients with mutations in PC-K6b have a milder form of PC, but experience painful plantar keratoderma as the most challenging feature.

• The condition is often not evident at birth, but onset is before age 15 for 90% of patients with PC-K6b.
  
• While nearly 100% have some toenail dystrophy, less than 50% have any fingernail dystrophy.
  
• Oral leukokeratosis is found in only a small percentage of PC-K6b patients and is usually mild.
  
• Cysts and follicular hyperkeratosis FHK are reported in many patients, although the cysts in PC-K6b are not as extensive as those in PC-K17.
  
• Plantar keratoderma and pain is experienced by nearly 100% of PC-K6b. Pain levels for PC-K6b patients are often from 3 to 7 on a 0 to 10 scale. This is less than PC-K6a, but significant pain levels.

IPCRR Data for PC-K6b

Plantar keratoderma and pain is experienced by nearly 100% of PC-K6b. Pain levels for PC-K6b patients are often from 3 to 7 on a 0 to 10 scale. This is less than PC-K6a, but significant pain levels.

Data from 2021 Sample Size N=93