Pachyonychia congenita

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Pachyonychia congenita is a condition that primarily affects the skin and nails. The signs and symptoms of this condition usually become apparent within the first few years of life.

Almost everyone with pachyonychia congenita develops very painful calluses on the soles of the feet. This condition is known as plantar keratoderma. Calluses usually begin to form on the feet in childhood when kids first start to walk. The calluses can make walking painful or impossible. In some affected individuals, blisters, bundles of blood vessels and nerves (neurovascular structures), or a deep itch may develop under or near the calluses, increasing pain and discomfort.

Most people with pachyonychia congenita also show some signs of hypertrophic nail dystrophy, which causes the fingernails and toenails to become thick and abnormally shaped. The number of affected nails varies.

Pachyonychia congenita can have several additional features. These features include thickened skin on the palms of the hands (palmar keratoderma), which can be painful; thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps that develop around hair follicles (follicular keratoses) 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 also develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that normally lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth, which are teeth that are present at birth or in early infancy. Some babies and children with pachyonychia congenita have pain in one or both ears when beginning to eat or drink. Pachyonychia congenita can also affect the voice box (larynx), causing hoarseness or breathing problems.

Researchers used to classigy pachyonychia congenita as either PC-1 or PC-2 based on the genetic cause and pattern of signs and symptoms. However, as more affected individuals were identified, it became clear that the signs and symptoms of the types overlapped considerably. Pachyonychia congenita is now classified into five types based on the gene that is altered.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the KRT6A, KRT6B, KRT6C, KRT16, or KRT17 genes cause pachyonychia congenita.

When pachyonychia congenita is caused by variants in the KRT6A gene, it is classified as PC-K6a. Similarly, KRT6B gene variants cause PC-K6b, KRT6C gene variants cause PC-K6c, KRT16 gene variants cause PC-K16, and KRT17 gene variants cause PC-K17.

All of the involved genes provide instructions for making tough, fibrous proteins called keratins. These proteins form networks that provide strength and resilience to the tissues that make up the skin, hair, and nails.

Variants in keratin genes alter the structure of keratin proteins. The altered proteins are unable to form strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. In people with pachyonychia congenita, normal activities such as standing and walking cause skin cells to break down, resulting in the formation of severe, painful blisters and calluses. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, resulting in the other features of pachyonychia congenita.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Pachyonychia congenita is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In about 60 to 70 percent of all cases, an affected person inherits the variant from one affected parent. Thirty to 40 percent of cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Pachyonychia congenita is a very rare disorder, although its exact prevalence is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hyperplastic callus formation · Very frequent (99-80%)

Increased growth of callus, the bony and cartilaginous material that forms a connecting bridge across a bone fracture during fracture healing.

Lower limb pain · Very frequent (99-80%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the leg.

Nail dystrophy · Very frequent (99-80%)

Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.

Onychogryposis of toenails · Very frequent (99-80%)

Thickened toenails.

Palmoplantar blistering · Very frequent (99-80%)

A type of blistering that affects the skin of the palms of the hands and the soles of the feet.

Palmoplantar keratoderma · Very frequent (99-80%)

Abnormal thickening of the skin of the palms of the hands and the soles of the feet.

Cutaneous cyst · Frequent (79-30%)

A hollow mass located in the skin that is surrounded by an epithelium-lined wall and is well demarcated from the adjacent tissue. Cysts are often said to be sac-like and may contain serous liquid or semisolid material.

Epidermoid cyst · Frequent (79-30%)

Nontender, round and firm, but slightly compressible, intradermal or subcutaneous cyst measuring 0.5-5 cm in diameter. Epidermal cysts are intradermal or subcutaneous tumors, grow slowly and occur on the face, neck, back and scrotum. They usually appear at or around puberty, and as a rule an affected individual has one solitary or a few cysts. A central, dark comedone opening (punctum) may be present.

Other findings in the same source

From: Orphanet

Additional reported features include Fingernail dysplasia (Frequent (79-30%)); Follicular hyperkeratosis (Frequent (79-30%)); Onychogryposis of fingernail (Frequent (79-30%)); Oral leukoplakia (Frequent (79-30%)); Palmar hyperkeratosis (Frequent (79-30%)); Palmoplantar hyperhidrosis (Frequent (79-30%)); Steatocystoma multiplex (Frequent (79-30%)); Linear arrays of macular hyperkeratoses in flexural areas (Frequent (79-30%)); Advanced eruption of teeth (Occasional (29-5%)); Ear pain (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Pachyonychia congenita is Dermatology, with a dermatologist as the relevant type of clinician. Dermatologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which features of the skin, hair or nails distinguish the possibilities?
• Would photographs over time help document the changes?
• What should be expected from treatment, and how will irritation or other adverse effects be managed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Pachyonychia congenita. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.