Kindler Syndrome

Excerpt

Clinical characteristics: Kindler syndrome (KS), a rare subtype of inherited epidermolysis bullosa, is characterized by skin fragility and acral blister formation beginning at birth, diffuse cutaneous atrophy, photosensitivity (most prominent during childhood and usually decreasing after adolescence), poikiloderma, diffuse palmoplantar hyperkeratosis, and pseudosyndactyly. Mucosal manifestations are also common and include hemorrhagic mucositis and gingivitis, periodontal disease, premature loss of teeth, and labial leukokeratosis. Other mucosal findings can include ectropion, urethral stenosis, and severe phimosis. Severe long-term complications of KS include periodontitis, mucosal strictures, and aggressive squamous cell carcinomas. Manifestations can range from mild to severe.

Diagnosis/testing: The diagnosis of KS is established in a proband with suggestive clinical findings and biallelic pathogenic variants in FERMT1 identified by molecular genetic testing.

Management: Treatment of manifestations: When possible, children with KS should be managed by a multidisciplinary team (dermatologist, pediatrician, ophthalmologist, dentist, gastroenterologist, urologist, nurse specialist, and dietitian) in a center experienced in caring for children with skin fragility. Skin care includes standard blister care, use of moisturizers, and protection from trauma and the sun. Mucosal involvement can require lubrication of the cornea, regular dental care to ensure optimal oral hygiene to reduce periodontal disease, and management of gastrointestinal and urethral complications.

Surveillance: Screening for premalignant keratoses and early squamous cell carcinomas starting in adolescence and repeated annually. Screening for oral ulcerations, gingivitis, and periodontitis starting in adolescence with regular dental checkups.

Agents/circumstances to avoid: Sun exposure.

Pregnancy management: Planning for potential complications at delivery (e.g., vaginal stenosis, labial synechiae). Breast-feeding is not advised due to risk of blistering breasts.

Genetic counseling: KS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an FERMT1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FERMT1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.