What Is Pachyonychia Congenita?

A rare, painful skin disorder that makes walking difficult and sometimes impossible

So much more than thick nails

Pachyonychia Congenita (PC) is a debilitating skin disorder that often goes undiagnosed. The word “pachyonychia” means thick nails and that name can be misleading, especially because patients deal with a host of issues, especially painful calluses on the bottoms of their feet.

PC is a genetic autosomal dominant skin disease caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. These mutations cause painful calluses, blisters, cysts, and yes, thickened nails. Sometimes all 20 nails may be thickened and other times, a barely thickened toenail is evident while the rest of the nails are flat. So despite the name, having PC means a whole lot more than thick nails.

Keratin genes are responsible for production of keratins, which are tough, fibrous proteins that form filaments to support skin cells and give them shape and strength. Keratin filaments help cells handle pressure and stretching. With PC, the filaments do not form properly, causing extreme cell fragility which is the reason walking is so painful for those who have a PC mutation.

The specific gene and mutation involved affects the disease condition for the PC patient. The different types of PC are classified as PC-K6a, PC-K6b, PC-K6c, PC-K16 and PC-K17 (related to the affected gene where the mutation is located).

The pain of PC can be so intense that many patients must regularly crawl at home.

On the left are normal (not PC) keratins that form a strong structural network that enables cells to withstand pressure and stretching. See the strong filaments (structures dyed with green) surrounding the nuclei of the cells (blue)? On the right are PC mutant keratins that form in clumps and don’t have that strong structure. They make for fragile cells which break under pressure. That is why PC skin is so tender. (Photos courtesy of Prof. W.H. Irwin McLean)

PC affects people of all ages, genders, ethnicities, and races. This disorder does not affect lifespan, but almost all patients experience chronic pain that makes walking difficult and sometimes impossible. Patients may use a variety of walking aids and crawling at home is common.

Read or view the Externally-Led Patient Focused Drug Development Meeting PC Project held with Food & Drug Administration (FDA) officials in 2018 to understand more about the challenges of living with PC.

PC is a lifelong skin disease that affects people of all ages, genders, races, and nationalities.

Symptoms of PC

Most Common

Thickened Nails (hypertrophic nail dystrophy or pachy-onychia) although not all nails are affected in all patients with PC. In fact, some patients may have only one thickened toenail.
Painful calluses and blisters on the soles of the feet (focal plantar hyperkeratosis). Pain is one of the distinct characteristics of PC. Blisters are found under the callus in PC patients. Calluses may also form on the palms of the hands (palmar hyperkeratosis).
Cysts of various types (including steatocystoma and pilosebaceous cysts). In some forms of PC, especially PC-K17, this is the most dominant, painful, and problematic characteristic.
Follicular hyperkeratosis (FHK or bumps around hairs at friction sites such as waist, hips, knees, elbows). Most common in children and lessens after during or soon after the teenage years.
Leukokeratosis of the oral mucosa (white film on tongue and inside cheeks). This is not painful, but is often misdiagnosed as thrush or as leukoplakia in young children.
Neurovascular Structures in Calluses (painful blood vessels or nerve endings). These can grow in the calluses and make trimming difficult and walking extra painful. They typically form at some point during adulthood.
Deep itch under, around, or in the calluses. Like the painful calluses, this deep itching can interfere with sleep and make the feet feel uncomfortable and irritable.

Less common

Sores at the corner of the mouth (angular cheilitis).
Teeth at or before birth (natal or pre-natal teeth). This is found in one subset of PC, PC-K17.
Laryngeal involvement with a white keratin film on the larynx. This results in a hoarse cry or a hoarse voice and is typically found in K6a babies. In some cases, this thickening can block the airway and become life-threatening. Immediate medical attention is needed at that point. Read an article about this feature of PC.
Intense pain with first bite (‘first bite syndrome’). The pain is near the jaw or ears and lasts 15–25 seconds when beginning to eat or swallow. This is more common in younger children and is often linked with ear problems. This phenomenon is still not well-understood and fortunately lessens as children get older. Right now, we do not know if it is this ear pain, or pain from the keratin build up on the tongue that sometimes make eating and sucking difficult for babies.