What is pachyonychia congenital?
Pachyonychia congenital is a rare genetic disorder that affects the skin and nails. The name Pachyonychia means thickened (patchy) nails (onychia), and congenita implies that this disease runs in the family. The pattern of inheritance for nearly 60 to 70% of cases is autosomal dominant, which means the child will inherit the disease when either the father or mother is affected. The other 30% were caused by new (de novo) mutations of the genes. The underlying genetic cause is a mutation in one of the five keratin genes, which can cause symptoms of pachyonychia congenita that usually become apparent soon after birth or within the few years of life. Adult-onset of this disease is rare.
How does mutation to keratin genes cause symptoms?
Keratin is a type of protein that makes up the hair, skin and nails. It functions to stick cells together and form a protective layer on the outside of the skin. In pachyonychia congenita, the mutations to the keratin genes alter the structure in the keratin proteins, thus preventing the proteins from forming a strong network of cells. Without this network, the skin becomes fragile, easily damaged and loses its protective function. Even normal friction like walking can cause skin cells to break off, resulting in severe, painful blisters and calluses. Since keratin is also found in nails and hair follicles, the growth and functions of these body parts are affected too in pachyonychia congenita.
How rare is pachyonychia congenita?
It is so rare that its prevalence and incidence are unknown. As of 2018, only 814 individuals who are genetically confirmed to have pachyonychia congenita were registered by the International Pachyonychia Congenita Research Registry.
What are the symptoms of pachyonychia congenita?
The predominant manifestations of pachyonychia congenita consist a triad of:
- thickened nails (hypertrophic nail dystrophy)
- thickened soles and palms (palmoplantar keratoderma)
- severe sole pain (plantar pain)
The thickening of fingernails and toenails is usually the first sign of pachyonychia congenita, usually occurring in the first few months to years of life. The affected nails either grow fully and curl upwards, or terminate prematurely, leaving exposed nail beds. As soon as the child starts to crawl and walk, palmoplantar keratoderma develops. Plantar keratoderma is the thickening of soles along with calluses and frictional blisters. Sometimes there are fissures and open wounds too. The same conditions can be seen on the palms. Due to this condition, the child suffers from severe and debilitating pain, especially on their soles. It can be so severe that their mobility and ability to perform daily life activities are greatly limited, affecting the quality of life.
In addition to the triad of symptoms, pachyonychia congenita also causes several other problematic features. One of them is oral leukokeratosis, which is white thick patches on the tongue and the inside of the cheeks. In infants, it can cause feeding difficulty. If the patches involve the larynx, children may have hoarseness and even breathing difficulty.
Another feature is cutaneous cysts that are found in the armpits, groin, back and scalp. Depending on the locations, cyst can cause pain and discomfort. Individuals usually develop these cysts after puberty and even into adulthood. Steatocystoma, a particular type of cyst filled with oily substance sebum may also be found widespread on the body. Some affected individuals develop bumps around the hair follicles called follicular hyperkeratosis, commonly on areas of friction like the elbows, knees and waistline. Palmoplantar hyperhidrosis, or excessive sweating on the palms and soles is also one of the symptoms. Lastly, some infants with pachyonychia congenita have prenatal teeth, which are teeth that are present at birth.