Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome

Overview

Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an exceptionally rare inherited skin disorder that affects the skin’s structure and function. It is characterized by a triad of features: linear keratosis (thickened, ridged skin along the limbs), ichthyosis congenita (generalized dry, scaly skin present from birth), and sclerosing keratoderma (hardening and thickening of the skin, particularly on the palms and soles). KLICK syndrome is present from early infancy and tends to persist throughout life. Although it primarily affects the skin, it can significantly impact quality of life due to discomfort and functional impairment.

Causes

KLICK syndrome is caused by mutations in the POMP gene (proteasome maturation protein gene). This gene is critical for the proper function of proteasomes, which are cellular structures involved in protein degradation and recycling. Mutations in POMP lead to proteasomal dysfunction, resulting in abnormal accumulation of proteins within skin cells and subsequent skin abnormalities. The disorder is inherited in an autosomal recessive manner, meaning both parents must carry one mutated copy of the gene for the child to be affected.

Symptoms

The key clinical features of KLICK syndrome include:

• Linear keratosis: Raised, ridged, thickened skin lesions along the arms and legs, often following Blaschko’s lines

• Ichthyosis congenita: Dry, scaly, or rough skin apparent from birth, sometimes resembling fish scales

• Sclerosing keratoderma: Diffuse thickening and hardening of the palms and soles, leading to reduced flexibility and possible pain with movement

Other associated findings may include:

• Skin fissures or cracking, especially on the feet

• Increased susceptibility to secondary skin infections due to compromised skin barrier

• Possible nail changes or discomfort during walking or hand movements

Diagnosis

Diagnosis of KLICK syndrome is based on clinical examination and confirmed by genetic testing. Diagnostic steps typically include:

• Detailed physical examination focusing on skin lesions, distribution patterns, and severity

• Skin biopsy, which may show characteristic histopathologic features like hyperkeratosis and abnormal protein accumulation

• Genetic testing to identify biallelic mutations in the POMP gene

• Family history evaluation, especially in cases with consanguineous parentage

Given its rarity, diagnosis often requires evaluation by a dermatologist familiar with genetic skin disorders.

Treatment

There is no cure for KLICK syndrome, and treatment is focused on symptom relief and improving skin condition. Management strategies include:

• Emollients and moisturizers: Regular use to soften the skin and reduce dryness and scaling

• Keratolytic agents: Topical treatments such as salicylic acid, urea, or lactic acid to reduce thickened skin

• Topical corticosteroids: For inflammation or irritation, used cautiously under supervision

• Oral retinoids: In severe cases, drugs like acitretin may help normalize skin turnover but require careful monitoring

• Protective footwear or gloves to reduce trauma and improve comfort in affected areas

• Treatment of secondary infections with appropriate antibiotics or antifungals as needed

Prognosis

The prognosis of KLICK syndrome is generally stable but chronic. While the condition is not life-threatening, it can lead to lifelong discomfort, cosmetic concerns, and functional limitations, especially in the hands and feet. With appropriate skin care and medical management, symptoms can be controlled to improve quality of life. Regular dermatologic follow-up is recommended to adjust treatment as needed and to address any complications such as fissures or infections.