Rekindle with Kindler Syndrome – Case Reports of a Rare Entity

INTRODUCTION

Kindler syndrome (KS), first identified by Theresa Kindler in 1954, is a rare inherited skin disorder transmitted in an autosomal recessive pattern. It falls within the spectrum of epidermolysis bullosa subtypes and is notable for its mucocutaneous involvement.^[1]

Additional variable features include infantile scarring, palmoplantar hyperkeratosis with fissures, pseudo-syndactyly and mucosal changes such as labial leucokeratosis, ectropion and urethral stenosis. Blistering and photosensitivity diminish with age but poikiloderma persists into adulthood. Adults with KS often experience chronic gum inflammation and dental complications, with an elevated risk of developing squamous cell carcinoma (SCC).^[2]

CASE REPORT

A 26-year-old woman, born to non-consanguineous healthy parents, presented with recent constriction bands and pain in the distal phalanges of both little fingers. History revealed trauma-induced acral blisters from birth to 5 years, childhood photosensitivity that subsided over time, and progressive skin changes on the face, neck and limbs. Examination showed poikiloderma with reticulate pigmentation, atrophy and telangiectasia over the face, V-area of the neck and upper chest. Both little fingers had distal constriction bands forming pseudoainhum. The dorsa of hands and feet displayed cigarette paper-like wrinkling with sclerodermoid changes, and the palms and soles were thickened, waxy, with reduced palmar creases [Figure 1a-d]. Oral mucosa was normal except for mild lower lip leucokeratosis. No gastrointestinal symptoms were reported, and the patient was otherwise healthy. Histopathology of acral skin showed non-specific changes of poikiloderma with epidermal atrophy and basal cell vacuolization. Lip lesion biopsy, done to exclude SCC, revealed epidermal hyperkeratosis with dermal inflammation and scarring, without malignancy. Based on clinical and histopathological finding differential diagnosis of dystrophic epidermolysis bullosa, dyskeratosis congenita and hereditary sclerosing poikiloderma were made. Further genetic testing by whole-exome sequencing was done to confirm the diagnosis, which showed Fermitin family member 1 (FERMT1) mutation in homozygous state on Exon 6 of chromosome 20 (Variant nomenclature c.811C > T [p.Arg271Ter], genomic nomenclature chr20:g.6088217G>A and zygosity homozygous) [Figure 2]. This variant has been previously reported in patients of KS by Kantheti et al., Chu et al. and Siegel et al.^[1-3] This confirmed the diagnosis of KS in our case. The patient’s 21-year-old brother (only sibling) had similar but milder findings: Childhood blistering and adolescent-onset poikilodermatous changes on face, neck and acral areas [Figure 3]. No other family members were affected. Genetic testing of sibling and other family members was not done due to cost constraints. Final diagnosis of autosomal recessive KS is considered for patient and her sibling.

Close

Figure 1:

(a) Poikiloderma: Manifested by hypopigmented and hyperpigmented macules reticular telangiectasia and epidermal atrophy of sun exposed skin. (b) Constriction over distal phalanx of both hands and decreased palmar creases. (c and d) Skin atrophy – cigarette paper-like wrinkled appearance on the dorsa of hands and feet.

Export to PPT

Close

Figure 2:

Genetic test report of proband.

Export to PPT

Close

Figure 3:

Poikilodermatous changes on acral area and neck in affected sibling.

Export to PPT

DISCUSSION

Around 400 cases of KS have been reported since 1954, with the highest concentration of 26 cases observed among the Ngobe Bugle population in Panama.^[2]

The genetic basis of KS was identified in 2003 and involves FERMT1 mutations on chromosome 20p12.3, which encode kindlin-1, a focal adhesion protein influencing keratinocyte shape, adhesion and migration through integrin-mediated signalling.^[3]

In India, KS remains exceedingly rare, with only a handful of cases reported in the literature. The most recent published case dates back to 2011, and notably, none of these have been genetically confirmed.^[4,5]

The presence of constriction bands on the fingers, as observed in our patient, is an uncommon manifestation and may represent a previously undocumented complication of recurrent blistering and trauma, potentially leading to pseudosyndactyly.

Diagnosis of KS is primarily clinical, supported by histopathological and immunofluorescence findings. Molecular confirmation through FERMT1 mutation analysis remains the gold standard. In 2005, Fischer et al. proposed diagnostic criteria based on hallmark clinical features, which continue to guide diagnostic evaluation.^[4,6]

Histologically, KS shows nonspecific poikilodermatous changes in affected skin, including epidermal flattening, basal layer vacuolization and pigment incontinence in the upper dermis. Transmission electron microscopy demonstrates basement membrane disorganization with multiple cleavage planes and lamina densa reduplication. Antigen mapping shows strong, broad, reticulate and branching staining with antibodies against laminin-332, type IV collagen, and type VII collagen. Anti-kindlin-1 immunostaining is also used as a diagnostic marker for KS.^[4] Final confirmation of KS is made by molecular genetic testing. Electron microscopy and antigen mapping were not done in our cases due to unavailability. Management of KS is largely supportive, focusing on minimising trauma, optimising wound care and preventing secondary infections. Laser t herapy may be beneficial for telangiectasia, while surgical intervention is sometimes necessary for mucosal stenosis. Psychosocial support and genetic counselling are essential components of long-term care. Differential diagnosis of KS variants of epidermolysis bullosa includes Rothmund-Thompson syndrome, Xeroderma Pigmentosa, Bloom syndrome, Dyskeratosis congenita and Weary syndrome. We report this case due to its rarity and available genetic report from Indian patient.

CONCLUSION

We report this case due to its rarity and confirmed genetic testing in Indian patient. Kindler syndrome, with its varied clinical features, carries significant morbidity and mortality and must be distinguished from other genetic disorders. Although no definitive treatment exists, management focuses on symptom relief and improving quality of life, with genetic counselling playing a crucial role.