Kindler syndrome

Overview

Kindler syndrome is a rare genetic skin disorder classified under a group of conditions known as inherited epidermolysis bullosa. It is characterized by skin fragility, blistering, progressive poikiloderma (a skin condition with mottled pigmentation, telangiectasia, and thinning), and photosensitivity. First described in 1954 by Theresa Kindler, the syndrome typically presents in infancy with skin blistering and evolves over time to include chronic skin damage and mucosal involvement. Although primarily affecting the skin, Kindler syndrome can also involve the eyes, oral mucosa, gastrointestinal tract, and genitourinary system.

Causes

Kindler syndrome is caused by mutations in the FERMT1 gene (also known as KIND1), which encodes the protein kindlin-1. This protein is involved in the adhesion between the epidermis and dermis and plays a role in the function of integrins—proteins critical for cell signaling and structural integrity. The syndrome is inherited in an autosomal recessive pattern, meaning both copies of the gene must be mutated for the condition to develop.

Symptoms

Symptoms of Kindler syndrome often appear in infancy or early childhood and evolve with age. Common features include:

• Skin blistering, particularly on hands and feet, usually present at birth or shortly thereafter

• Photosensitivity (increased sensitivity to sunlight)

• Poikiloderma: a combination of skin thinning, irregular pigmentation, and visible small blood vessels

• Skin atrophy (thin, fragile skin prone to injury)

• Progressive skin wrinkling, particularly on the backs of hands and feet

• Gingivitis and periodontitis due to mucosal fragility

• Urethral or anal stenosis in severe cases

• Esophageal strictures or gastrointestinal involvement in some patients

Diagnosis

Diagnosis of Kindler syndrome involves a combination of clinical evaluation, histological analysis, and genetic testing. Diagnostic steps include:

• Clinical examination for characteristic skin and mucosal findings

• Skin biopsy showing abnormalities at the dermal-epidermal junction, often involving multiple cleavage levels

• Immunofluorescence mapping and electron microscopy to assess protein expression and skin ultrastructure

• Genetic testing to confirm mutations in the FERMT1 gene

Early genetic diagnosis can assist with management and family counseling.

Treatment

There is no cure for Kindler syndrome, and treatment is supportive and symptom-based. Management strategies include:

• Wound care: Gentle handling, use of non-adhesive dressings, and prompt treatment of blisters and erosions

• Sun protection: Sunscreens, protective clothing, and avoidance of prolonged sun exposure

• Skin care: Emollients and moisturizers to prevent dryness and cracking

• Dental care: Regular oral hygiene and dental visits to manage gingivitis and prevent periodontal disease

• Monitoring for complications: Surveillance for urethral, anal, or esophageal strictures; endoscopy or imaging may be needed

• Psychosocial support: Counseling and patient education to improve quality of life

Prognosis

The prognosis for individuals with Kindler syndrome varies based on the severity of symptoms and associated complications. While the condition does not typically affect life expectancy, it can significantly impact quality of life due to chronic skin damage, mucosal involvement, and increased risk of infections or strictures. With appropriate skin care, sun protection, and multidisciplinary management, many individuals can lead relatively normal lives. Regular follow-up with dermatology and other specialists is important for early detection and treatment of complications.