What are the other Names for this Condition? (Also known as/Synonyms)

• KLICK Syndrome

What is Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome? (Definition/Background Information)

• Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome (KLICK Syndrome) is a rare genetic disorder characterized by abnormal skin thickening and scaling, often accompanied by hair and nail changes
• It is caused by mutations in the POMP gene that provides instructions for making the POMP protein. When this gene is mutated, it leads to the development of abnormal skin thickening and scaling of the palms and soles and other characteristic sites on the skin
• Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome is inherited in an autosomal recessive manner, and the only known risk factor for KLICK Syndrome is having a family history of the disorder
• The signs and symptoms include thickened, inflexible callous-like skin of the palms and soles (ichthyosis congenita), with stripe-like thickening of wrists, arm folds opposite the elbows and behind the knees (keratosis linearis), and a condition where the thickened skin renders the fingers inflexible or encircles fingers (sclerosing keratoderma) 
• Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome is diagnosed by a combination of clinical findings and laboratory tests. A skin biopsy can confirm the presence of abnormal thickening and scaling. Genetic testing can confirm the presence of a mutation in the POMP gene
• The treatment typically includes the use of emollients and topical creams to moisturize and soften the skin. In severe cases, oral retinoids or other systemic medications may be needed to control the symptoms. The prognosis for KLICK Syndrome is generally excellent with appropriate treatment; most of the individuals are able to lead a good quality of life

Who gets Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome? (Age and Sex Distribution)

• Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome (KLICK Syndrome) is a rare disorder with a congenital manifestation (it may occur at birth)
• The disorder affects both males and females
• Worldwide, KLICK Syndrome may affect individuals of all races and ethnic groups

What are the Risk Factors for Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome? (Predisposing Factors)

• The only known risk factor for Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome is a positive family history of the disorder
• It may be more frequent in pairings (couples) with significant similar genetic material (such as due to consanguineous marriage)
• Inheriting two copies of the mutated POMP gene, one from each parent, to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome? (Etiology)

The cause of development of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome (KLICK Syndrome) is a mutation in the POMP gene. It is inherited in an autosomal recessive manner.

• The POMP gene provides instructions for making the POMP protein that functions as a chaperone for proteasome maturation of the skin, hair, and nails (keratinization of skin)
• When this gene is mutated, it leads to the development of abnormal skin thickening of the epidermis and the non-living keratin layer (stratum corneum)
• KLICK Syndrome mainly affects the palms and soles and other characteristic sites on the skin

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome?

The signs and symptoms of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome include:

• Thickened and scaly skin on the palms and soles (ichthyosis congenita)
• Patterned stripe-like rough keratinized lines on the skin of the wrists, folds of the arms, and behind the knees (keratosis linearis)
• Sclerosing keratoderma, a condition characterized by thick, waxy skin on the palms, soles, and fingers. It can restrict finger motion and encircle fingers

How is Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome Diagnosed?

• Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome is diagnosed by a combination of clinical findings and laboratory tests
• A skin biopsy can confirm the presence of abnormal thickening and scaling
• Genetic testing can confirm the presence of a mutation in the POMP gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome?

The complications of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome can include:

• Difficulty with fine motor tasks due to thickened skin on the hands and feet
• Skin infections - secondary bacterial or fungal infections
• Overall, reduced quality of life

How is Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome Treated?

• Treatment for Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome typically includes the use of emollients and topical creams to moisturize and soften the skin
• In severe cases, oral retinoids or other systemic medications may be needed to control the symptoms

How can Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome be Prevented?

Presently, it is not possible to prevent Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome as the cause is a genetic mutation. 

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome? (Outcomes/Resolutions)

The prognosis for Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome is generally excellent since no major body systems are affected. This means that the disorder has skin keratinization abnormalities only, and all other vital body systems remain unaffected.

• Most of the affected individuals can lead normal lives with an improved quality of life
• A management of the disorder is directed at improving skin flexibility and appearance
• However, in some cases, the disorder can affect the patient’s sense of well-being and make them self-conscious.

Additional and Relevant Useful Information for Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma Syndrome:

The POMP gene causing KLICK Syndrome is also causative in proteasome-associated autoinflammatory syndrome 2 (PRAAS2), another autoinflammatory disease (AID). Both disorders have varying sets of signs and symptoms.