Kindler's Syndrome: A Tale of Two Siblings.

Kindler's syndrome (KS) is a rare inherited skin disease characterized by acral blistering, photosensitivity, progressive poikiloderma, and cutaneous atrophy along with different types of mucosal involvement. We hereby report KS in two siblings. The case is being reported for its rarity and for emphasizing the importance of considering this condition in the differential diagnosis of disorders that may cause blistering, cutaneous atrophy, and/or poikilodermatous skin changes. Besides, the presentation of the disease in two of the members of the same family makes the case even more interesting.

What was known?

Kindler's syndrome is a rare inherited skin disease characterized by acral blistering, photosensitivity, progressive poikiloderma, and cutaneous atrophy along with mucosal involvement.

Introduction

Kindler's syndrome (KS) is a rare autosomal recessive genodermatosis which is characterized by the presence of trauma-induced blisters, progressive poikiloderma, variable extent of photosensitivity, diffuse cutaneous atrophy, abnormal pigmentation, and fragility of skin. The disease was first mentioned in 1954 by Theresa Kindler in a 14-year-old girl with acral blistering since childhood who subsequently developed poikiloderma and photosensitivity.[1] We hereby report two siblings who were diagnosed with KS.

Case Reports

Case 1

A 5-year-old boy, born of nonconsanguineous parentage, presented with a history of repeated blistering, mainly involving the dorsum of the hands and feet since birth. Some blisters were spontaneous, whereas others were traumatic. The blisters contained a clear fluid and the blisters ruptured with scar formation. Subsequently, he developed photosensitivity with burns at the slightest exposure to sunlight. On cutaneous examination, hyperpigmentation was present on malar area of cheeks extending to the preauricular area [Figure 1]. Poikiloderma was present in the V area of the neck, multiple hyperpigmented macules of size varying from 0.2 to 1 cm were distributed over the trunk, abdomen, and back [Figures 1 and 2]. The dorsum of the hands and feet had marked cigarette paper-like wrinkling [Figure 3].

Figure 1

Multiple, hyperpigmented macules distributed over the face, neck, and trunk. Note the poikilodermatous skin changes on the V area of neck, anterior aspect (Case 1 and 2)

Figure 2

Similar poikilodermatous changes on the posterior aspect (Case 1 and 2)

Figure 3

Dorsum of hands showing cigarette paper-like wrinkling (Case 1)

Case 2

Our second case was the 3-year-old sister of our first patient. According to her parents, there was a history of acral blistering, which started on the 3rd day of the neonatal period, but the tendency to blistering had decreased gradually over time. Besides, there was a history of intolerance to sunlight. Examination revealed multiple, hyperpigmented macules of variable sizes, distributed over the face, neck, trunk, and limbs. Poikilodermatous skin changes were present on the V area of neck [Figures 1 and 2]. There was a fresh fluid-filled bulla on the dorsum of left foot [Figure 4]. She also had cigarette paper-like wrinkling of the dorsum of hands and feet [Figure 5]. Gingivitis was present in this patient [Figure 6].

Figure 4

Bulla on the dorsum of left foot (Case 2)

Figure 5

Dorsum of hands showing cigarette paper-like wrinkling (Case 2)

Figure 6

Note the inflammation of gums (Case 2)

The maternal uncle of the children had a similar illness, characterized by acral blistering and atrophy of skin over the dorsum of hands. The photosensitivity was milder. In both the patients, palmoplantar keratoderma, palmar pits, and nail abnormalities were absent. However, the palms had a glazed appearance, and the dermatoglyphics were reduced to some extent [Figure 7]. Mental and motor development was normal. Some of the scalp hairs were light brown to golden in color in both the patients [Figure 8]. Ophthalmic, dental, and systemic examination was normal. Routine laboratory examinations including complete hemogram, renal profile, and hepatic profile were normal. Urine and stool porphyrin levels were within normal limits. Histopathological examination showed atrophic epidermis, marked basal cell vacuolar degeneration and cleft formation at multiple levels in the dermo-epidermal junction [Figure 9]. Direct immunofluorescence did not reveal any deposition of immunoglobulins or complements. Genetic analysis, electron microscopy and immunostaining could not be done due to unavailability of resources and financial constraints. Symptomatic treatment was given to the patients in the form of sunscreens, antibiotics. Besides, the parents were counseled regarding avoidance of trauma and direct exposure to sunlight.

Figure 7

Glazed appearance of palms and reduction of dermatoglyphics (Case 1)

Figure 8

Golden brown color of the hair on the scalp (Case 2)

Figure 9

Photomicrograph showing atrophic epidermis, marked basal cell vacuolar degeneration and cleft formation at multiple levels in the dermo-epidermal junction (H and E, ×100)

Discussion

KS is a rare genodermatosis characterized by congenital acral skin blistering, photosensitivity, progressive poikiloderma, and diffuse cutaneous atrophy. The autosomal recessive pattern of transmission has been reported, but sporadic cases are not uncommon, with numerous cases reported in consanguineous families. Variable expressivity within families has also been documented. The KIND1 gene mutated in KS codes for the protein kindlin-1, which is a membrane-associated signaling protein that links the actin cytoskeleton to the extracellular matrix.[2] Besides, a novel mutation in FERMT1 gene has been recently discovered.[3]

The disease manifests at birth with blistering of skin induced by trauma, more prominent over the limbs which regress with age. The blisters heal with minimal scarring. Photosensitivity can manifest as increased susceptibility to sunburn. Blistering and photosensitivity begin in infancy or early childhood and improve significantly with age. Diffuse poikiloderma appears gradually and becomes more prominent later in life and is predominantly localized to the face and neck. Atrophic changes (cigarette paper-like wrinkled appearance of the skin) are most prominent in sun-exposed areas, most commonly on the dorsal aspect of the hands and feet but become generalized by adolescence. The incidence of appearance of blisters and photosensitivity tend to reduce with age, but the atrophy and poikiloderma are persistent.

Blisters also affect the mucosae. In the oral cavity, chronic gingivitis, dental caries, periodontitis, advanced periodontal bone loss, and leukokeratosis of buccal mucosa are frequent and prominent features in adulthood. Esophageal strictures, anal stenosis, rectal bleeding, urethral bleeding, meatal stenosis, ectropion, keratoconjunctivitis, and conjunctival scarring have also been described.[4] Other less common and variable features include ichthyosis, milia, palmoplantar hyperkeratosis, blond hair,[5] pseudoainhum, nail dystrophy, long and thick cuticle of nail,[67] severe corneal ectasia,[8] and an increased susceptibility to the development of squamous cell carcinoma.[910] In a recent report, acquired adermatoglyphia has been hypothesized to be an additional feature of KS.[11]

Diagnosis is essentially clinical. Histopathologic examination of atrophic skin lesions in patients with KS shows nonspecific features of poikiloderma such as epidermal atrophy, vacuolar degeneration of basal layer, edema at the dermo-epidermal junction, pigment incontinence, and dilatation of blood vessels in the papillary dermis. Biopsy of blistered skin samples by immunofluorescence antigen mapping and transmission electron microscopy shows single or multiple cleavage planes at the level of the cutaneous basement membrane zone as well as an extensive reduplication of the lamina densa. Ultrastructural studies show intraepidermal, junctional, and dermal cleavage. Immunostaining with anti-kindlin-1 antibody shows decreased staining of the epidermis in KS.[12]

It is essential to differentiate this syndrome from Weary's syndrome, epidermolysis bullosa (EB) and other congenital poikilodermatous and photosensitive conditions. In the neonatal period, it is important to rule out EB as it presents with similar features. The appearance of poikiloderma and decreased tendency to form blisters as the patient grows older helps in ruling out EB. KS has to be differentiated from various syndromes causing photosensitivity. Poilkiloderma can also be seen in Rothmud–Thompson but it is also associated with sparse hair, cataract, short stature, and hypogonadism. Bloom's syndrome is characterized by photo-telangiectatic erythema over the malar areas, short stature, and increased predisposition to malignancy. In addition to photosensitivity, xeroderma pigmentosum is associated with eye and neurological abnormalities and increased chances of development of actinic keratosis, squamous cell carcinoma, and basal cell carcinoma. Cockayne syndrome is characterized by cachectic dwarfism, retinopathy, and mickey mouse facies. In Weary syndrome or acrokeratotic poikiloderma, blisters appear within 6 months of life but are not present at birth that is a feature of KS.[13]

Treatment is mainly symptomatic and preventive in nature. Use of topical and systemic antibiotics for infected bullous lesions may reduce morbidity. Patients should be advised to avoid trauma and photoprotection should be advocated which may prevent or slow the progression of poikiloderma.[14] The life span of these patients usually remains unaltered. However, the mucosal involvement in the form of strictures, stenosis, oral complications, etc., leads to a significant deterioration in the quality of life.[15]

In such cases, symptomatic management with proper counseling forms the keystone of therapy.

According to the diagnostic criteria proposed by Fischer et al., the presence of four major criteria makes a diagnosis of KS.[16] The major criteria include acral blistering beginning in infancy, progressive poikiloderma, cutaneous atrophy, photosensitivity, and fragility and/or swelling of gums. The minor criteria are syndactyly and involvement of other mucosae. Additional features include onychodystrophy, palmoplantar keratoderma, ectropion, pseudoainhum, leukokeratosis of lips, squamous cell carcinoma, anhidrosis, skeletal abnormalities, and dental problems. The diagnosis is “confirmed” in the presence of four major criteria. The presence of three major and two minor criteria makes a “probable” diagnosis, and diagnosis is considered to be likely if two major and two minor/additional features are present. Both our patients had all four major criteria, and thus, these were “confirmed” cases of KS.

In this paper, we report the presence of KS in siblings of nonconsanguineous parents, with the presence of acral blistering, photosensitivity, poikiloderma, and cutaneous atrophy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

We have presented a report of two siblings affected by Kindler's syndrome, which is a rare occurrence. Besides, the literature has been reviewed.