SNP Shot: Genomic Insights

Pachyonychia congenita is a disorder primarily affecting the skin and nails, with symptoms typically emerging in early childhood.

A hallmark of pachyonychia congenita is the development of painful calluses on the soles of the feet (plantar keratoderma). These calluses often appear when children begin walking and can make ambulation difficult or agonizing. In some instances, blisters, neurovascular structures, or intense itching may occur under or near the calluses, exacerbating the pain and discomfort.

Most individuals with pachyonychia congenita also experience hypertrophic nail dystrophy, causing thickened and misshapen fingernails and toenails. The number of affected nails varies from person to person.

Other features can accompany pachyonychia congenita, including painful thickening of the skin on the palms of the hands (palmar keratoderma); white patches on the tongue and inside the cheeks (oral leukokeratosis); follicular keratoses (bumps around hair follicles) on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis).

Some affected individuals may also develop steatocystomas, which are widespread cysts filled with sebum, an oily substance that normally lubricates skin and hair. Certain infants with pachyonychia congenita are born with or develop natal teeth (teeth present at birth or in early infancy). Some babies and children experience ear pain when eating or drinking. The condition can also affect the larynx, leading to hoarseness or breathing difficulties.

Previously, pachyonychia congenita was classified as PC-1 or PC-2 based on genetic cause and symptom patterns. However, with the identification of more affected individuals, the overlap in signs and symptoms became evident. Currently, pachyonychia congenita is classified into five types according to the specific gene that is altered.

Inheritance:

Pachyonychia congenita follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. In approximately 60-70% of cases, the affected individual inherits the altered gene from a parent who also has the condition. In the remaining 30-40% of cases, the condition arises from a new (de novo) genetic mutation during the formation of reproductive cells (eggs or sperm) or during early embryonic development. These cases occur in individuals with no family history of pachyonychia congenita.