Pachyonychia congenita

background

Pachyonychia congenita (PC) is one of the ectodermal dysplasias, a group of syndromes deriving from abnormalities of the ectodermal structures, which include the hair, teeth, nails, sweat glands, cranial-facial structure, and hands. Ectodermal dysplasias are genetic disorders that can be inherited in an autosomal dominant or recessive manner.
While various classifications for PC have been proposed, only two forms of the condition are recognized: type I (PC-1) and type II (PC-2). However, there may be more types of PC, including type III (PC-3), and a form of PC that develops later in life, known as PC tarda, or PC late.
The signs and symptoms of PC typically appear within the first few months of life and include hypertrophic nail dystrophy, which causes the fingernails and toenails to become thickened and abnormally shaped; and palmoplantar keratoderma (painful calluses and blisters on the soles of the feet and, less commonly, on the palms of the hands). Other symptoms include oral leukokeratosis (thick, white patches on the tongue and insides of the cheeks); follicular keratoses, which are bumps that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and palmoplantar hyperhidrosis (excessive sweating on the palms and soles). Rarely, the condition can affect the larynx (voice box), potentially leading to hoarseness or breathing problems. These complications vary among affected individuals. PC-1 and PC-2 are distinguished by their genetic cause and by their signs and symptoms. Both types are associated with the features described above, but PC-2 has several additional signs that are not typically seen in PC-1. For example, most people with PC-2 develop widespread cysts called steatocystomas during puberty. People with PC-2 are also more likely to have twisted or kinked, brittle, and coarse hair. Additionally, some babies with PC-2 have prenatal or natal teeth, which are present at birth or in early infancy.
Pachyonychia congenita (PC) is a rare genetic disorder that is caused by a single mutation in any one of four keratin genes known as K6a, K6b, K16 or K17. K6a and K6b are located on chromosome 12, while K16 and K17 are located on chromosome 17. Keratin proteins are tough, insoluble, structural proteins that grow from the skin and include hair and nails. Mutations in keratin genes K6a or K16 cause PC-1, while mutations in keratin genes K6b and K17 cause PC-2. PC-1 is more common than PC-2.
PC is an inherited disorder, meaning that is passed down among family members. For both types of the disorder, PC follows an autosomal dominant pattern of inheritance, meaning that only one copy of the defective gene is needed for the disease to appear in either males or females. There have also been reports of PC following a recessive pattern, in which an individual must inherit two copies of the defective gene for the disease to appear.
PC is extremely rare, with only a few reported cases in the United States. The Pachyonychia Congenita Project Mission Statement, which is a consortium of scientists and doctors that works to find a cure for this disease, claims there are fewer than 300 known cases worldwide. There have been clusters of cases in Slovenia, Croatia, China, and Italy. The worldwide incidence is not known but is estimated at 70 cases in 10 million people in Slovenia and 53 cases in 10 million people in Croatia. However, all races and ethnicities are likely to be equally affected. In addition, males and females are affected in equal numbers.
Although there is no cure for PC, it is not a fatal disorder. Treatments aim to reduce symptoms and prevent complications. Individuals with PC have normal life expectancies.

Related Terms

Ectodermal dysplasia, Jadassohn-Lewandowsky syndrome, K6a, K6b, K16, K17, keratin, KRT6A, KRT6B, KRT16, KRT17, pachyonychia congenita hereditaria, pachyonychia congenita Jackson-Lawler type, pachyonychia congenital late, pachyonychia congenita recessive, pachyonychia congenita tarda, pachyonychia congenita type I, pachyonychia congenita type II, pachyonychia congenital type III, PC-1, PC-2, PC-3, PC-4.

types of the disease

General: There are two main types of pachyonychia congenita (PC): PC-1 and PC-2. PC-3 and PC-4 have not been well studied and therefore are mentioned here only briefly. Only PC-1 and PC-2 are recognized as subtypes of this condition.
PC-1: PC-1, also known as Jadassohn-Lewandowski syndrome, is the most common form of the disease and is associated with mutations in keratin genes K6a (KRT6A) or K16 (KRT16). PC-1 is associated with nail symptoms and leukokeratosis (thick, white patches on the tongue, throat, gums, and insides of the cheeks).
PC-2: PC-2, also known as Jackson-Lawler syndrome, is less common than PC-1 and is associated with slightly different symptoms and disease severity. PC-2 is caused by mutations or defects in keratin genes K6b (KRT6B) or K17 (KRT17). PC-2 is associated with natal teeth (teeth that are present at birth) and cystic growths of the skin, but less severe leukokeratosis and other skin symptoms. Patients with PC-2 may also develop cataracts.
PC-3: Some researchers have described a syndrome they call PC-3, which is similar to PC-1 but also includes hair defects and white patches on the corneas of the eyes.
PC-4: A fourth type, PC tarda, develops later in life, sometimes as late as one's 30s. Researchers believe that this type is also inherited as an autosomal dominant trait, meaning that only one copy of the defective gene is necessary for the disease to appear.