Kindler Syndrome

Kindler Syndrome is a rare inherited disorder characterized by skin fragility, photosensitivity, and progressive poikiloderma. It is caused by mutations in the FERMT1 (KIND1) gene, which encodes kindlin-1, a protein essential for integrin activation and signaling.

Key Points

• Autosomal recessive inheritance pattern
• First described by Theresa Kindler in 1954
• Prevalence: Less than 1 in 1,000,000
• Characterized by the triad of:
  • Congenital skin fragility
  • Photosensitivity
  • Progressive poikiloderma

Cutaneous Manifestations

• Acral blistering (beginning in infancy)
• Progressive poikiloderma (atrophy, pigmentary changes, and telangiectasia)
• Photosensitivity
• Diffuse cutaneous atrophy
• Cigarette paper-like wrinkling
• Webbing between fingers and toes
• Palmoplantar keratoderma

Extracutaneous Features

• Mucosal Involvement:
  • Gingivitis and periodontitis
  • Esophageal strictures
  • Anal stenosis
  • Urethral stenosis
• Ophthalmologic:
  • Ectropion
  • Conjunctival scarring

Age-Related Progression

1. Infancy:
   • Acral blistering
   • Photosensitivity
2. Childhood:
   • Development of poikiloderma
   • Skin atrophy
3. Adolescence/Adulthood:
   • Progressive mucosal involvement
   • Increased risk of squamous cell carcinoma

Diagnostic Criteria

Major Criteria (4 out of 5 required):

• Acral blistering in infancy and childhood
• Progressive poikiloderma
• Skin atrophy
• Photosensitivity
• Gingival fragility/periodontal disease

Laboratory Investigations

• Genetic testing:
  • FERMT1 gene sequencing
  • Detection of pathogenic variants
• Skin Biopsy Findings:
  • Epidermal atrophy
  • Pigmentary incontinence
  • Dermal fibrosis

Differential Diagnosis

• Epidermolysis bullosa
• Rothmund-Thomson syndrome
• Bloom syndrome
• Xeroderma pigmentosum
• Weary-Kindler syndrome

Treatment Approach

• Preventive Measures:
  • Sun protection (broad-spectrum sunscreens)
  • Trauma prevention
  • Regular dental care
• Wound Care:
  • Appropriate dressings
  • Infection prevention
  • Topical antibiotics when needed
• Management of Complications:
  • Regular dental check-ups
  • Endoscopic dilation for esophageal strictures
  • Regular skin cancer screening

Monitoring

• Regular dermatological examination
• Dental monitoring
• Gastrointestinal surveillance
• Ophthalmological check-ups
• Screening for squamous cell carcinoma

Genetic Basis

• Gene: FERMT1 (KIND1)
  • Location: Chromosome 20p12.3
  • Protein product: Kindlin-1
• Inheritance:
  • Autosomal recessive pattern
  • Both parents must be carriers
• Molecular Mechanism:
  • Loss of kindlin-1 function
  • Disrupted integrin activation
  • Compromised cell-matrix adhesion

Genetic Counseling

• 25% risk of affected offspring if both parents are carriers
• Importance of family planning
• Possibility of prenatal testing