Kindler syndromeQ87.1

Brain, 1952; Theresa Kindler, 1954; Weary 1971.

The term refers to the doctor Theresa Kindler, who described the clinical picture in detail.

Autosomal recessive inherited, fourth, independent form of the hereditary epidermolysis bullosa group. Very rare poikilodermatic clinical picture with "variable" blister formation (intraepidermal in the basal keratinocytes, junctional, dermal). The syndrome is caused by a mutation in the FERMT1 gene (gene locus: 20p12.3), which codes for the Kindler protein (Kindlin-1).

Some authors separate:

• Weary type with autosomal dominant inheritance
• from the
• Kindler type with autosomal recessive inheritance.

The molecular pathology of Kindler syndrome is known. Detection of a "loss of function" mutation of FERMT1 (KIND1 gene), which is localized on chromosome 20p12.3. This gene encodes Kindlin-1, a membrane-associated structural protein that is mainly expressed in basal keratinocytes. Kindlin-1 links the actin in the cytoskeleton to the extracellular matrix. Kindlin-1 is involved in the cell adhesion of epithelial cells. It contributes to integrin activation. When co-expressed with talin, it enhances the activation of ITGA2B. A total of 59 different mutations have been described to date (Youssefian L et al. (2015).

Kindlin-1 is required for normal keratinocyte proliferation, normal polarization of basal keratinocytes in the skin and normal cell shape. Kindlin-1 plays a major role in the adhesion of keratinocytes to fibronectin and laminin and in the normal migration of keratinocytes to wounds. May mediate TGF-beta 1 signaling during tumor progression.

Especially girls. Blisters: Usually from birth or a few months later. Poikiloderma: Until the age of 4. The formation of blisters decreases with age.

An increased rate of disease is found in the Ngöbe - Bugle Indians. The Ngöbe-Bugle are an ethnic minority of the Chibcha, who have settled in the province of Chiriqui (province in Panama).

Integument: Blistering manifest from birth with developing poikiloderma. Spontaneous or post-traumatic subepidermal blisters, poikiloderma in mentioned localization (picture resembles systemic scleroderma), photosensitivity, verrucous hyperkeratosis of palmae, synechiae on fingers and toes, resulting in a pseudosyndactyly clinical picture with poikiloderma. Mostly nail dystrophies and hypotrichosis.

Oral mucosa is fragile and bleeds easily. Many patients develop marked gingivitis.

No oral leukoplakia and no cataract.

Aggressive squamous cell carcinoma of the skin and/or mucous membranes is a serious complication.

Other associated symptoms: dental anomalies, skeletal malformations, proportioned short stature; esophageal stenosis, urethral strictures.

Subepidermal blisters, fibrinoid corpuscles below the dermoepidermal basement membrane zone.

Electron microscopic: reduplications of the basal lamina, fine fibrillar cell-sized corpuscles in the papillary body.

Kindler syndrome is often diagnosed as EB at birth due to the considerable overlap with dystrophic EB and EB simplex with patchy pigmentation.

Later, however, the development of progressive skin atrophy and poikiloderma, acral blistering, mucosal inflammation and photosensitivity are diagnostic, and the diagnosis can be confirmed by the detection of loss-of-function mutations in the FERMT1 gene.

Dyskeratosis congenita.

Symptomatic. Avoid mechanical irritation and irritation to reduce blister formation and monitor and treat secondary infections.

Drying and antiseptic solutions such as quinolinol solution(1:1000), R042 or potassium permanganate solution(light pink). S.a.u. Wound treatment. Adequate fluid replacement. Sterile lancing and draining of blisters prevents expansion and relieves pressure. The bladder roof should be left in place to protect against infection.

External glucocorticoids only for eczematization and pruritus such as 0.1% triamcinolone acetonide cream R259. General care of the skin e.g. with Ungt. emulsif. aq.

Important: Consistent light protection

Decrease in blister formation with increasing age. Conspicuous and increasing poikilodermatic, also scleroderma-like picture.

S.a. Hereditary sclerosing poikiloderma

Initial experimental attempts have been made to restore the structure of the skin and other important physiological functions by repairing the known mutation.

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2. Binder B et al (2002) Congenital bullous poikiloderma (Kindler syndrome). Dermatologist 53: 546-549
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11. Wendenburg WW et al (1992) Brown-Falco-Marghescu syndrome. Congenital poikiloderma with blistering. Act Dermatol 18: 141-144

12. Youssefian L et al.(2015) The Kindler Syndrome: A Spectrum of FERMT1 Mutations in Iranian Families. Journal of Investigative Dermatology 135: 1447-1450