Kindler syndrome is a rare autosomal recessive genodermatosis, which presents itself in infancy. The disease is characterized by neonatal blistering, photosensitivity, progressive poikiloderma, diffuse cutaneous atrophy, abnormal pigmentation, and skin fragility. Ultrastructurally, marked basement membrane reduplications and cleavages at the dermal-epidermal junctions can be visualized. As age advances, the blistering and sun sensitivity tends to improve, although the abnormal pigmentation and basement thinning may worsen. In addition to these main features, occasionally, palmoplantar keratoderma, nail abnormalities, gingival fragility, poor dentition, and finger webbing may also be seen. Further rare complications of Kindler syndrome include a tendency towards squamous cell carcinoma of the hard palate, lip, and urinary bladder.
Ever since its first report in 1954, more than 100 cases of this disease have been reported in literature. The most significant of these is a cluster of 26 patients in a tribe from Panama. Differential diagnoses to be considered while considering this condition include congenital bullous diseases like epidermolysis bullosa, congenital poikilodermas and photosensitivity disorders like the Rothmund-Thompson syndrome, and other photosensitivity disorders related to defective DNA repair like Xeroderma Pigmentosum and Cockayne syndrome. Management of the disease is symptomatic and preventive. Protecting the skin from the sun is important. Since blister formation is encouraged by trauma, it is advised to avoid any kind of trauma. Infected bullous lesions may require antibiotics.
Jobard et al. (2003) described three Algerian families with patients affected with Kindler syndrome. The first family had three affected children (2 females, 1 male) born to consanguineous, though healthy parents. The clinical features noticed were acral blistering at birth, photosensitivity, progressive poikiloderma with dyschromatic macules, telangiectases, cutaneous atrophy, sclerodermiform fingers, and leucokeratotic plaques on the oral mucosa. Four other siblings were normal. The second family had a 9-year-old affected daughter born to consanguineous parents, who presented with a similar phenotype and also suffered form aortic insufficiency. Two other siblings and both parents were normal. The third family had a 13-year-old affected boy and a 6-year-old affected girl. These patients were also born to healthy parents, who were second-cousins. The boy presented with poikiloderma with photosensitivity, blisters on the arms, legs and oral mucosa, diffuse ichthyosis and reticular hyperpigmentation on the trunk, thin and dry hair, nail dystrophy, webbing of the fingers, and phimosis, along with chronic diarrhea. His skin biopsy revealed hyperkeratosis, mild fibrosis of the upper dermis, free melanin, and melanophages. His sister's features were similar, but milder [See also > Tunisia > Jobard et al., 2003].
Hacham-Zadeh and Garfunkel (1985) described two Kurdish Jewish families, related to each other through a common great-grandfather, with members affected with Kindler syndrome. The first family had a 19-year old daughter, born to consanguineous parents. Both parents and five other siblings were normal. This patient presented with atrophic scars left by healing of bullae on pressure areas of the skin, marked atrophy of the skin of the palms and soles, wrinkled skin on the dorsa of feet and hands, photosensitivity, and poikiloderma; all present since birth. The second family had three affected children, born to healthy consanguineous parents, with similar symptoms.
Siegel et al. (2003) identified the nonsense mutation 193C>T in exon 3 of the KIND1 gene, predicting amino acid change Q65X, in a consanguineous Jordanian family with two siblings affected with Kindler syndrome. [See also: Oman > Siegel et al., 2003].
In an attempt to identify the genetic basis of Kindler syndrome, Siegel et al. (2003) confirmed the location of the locus identified by Jobard et al. (2003) in the Panamanian families and in individuals with Kindler syndrome from diverse geographic backgrounds, some of whom had previously been described (Al Aboud et al., 2002). Siegel et al. (2003) studied affected and healthy members from 24 families, including consanguineous families from Oman, Jordan, Saudi Arabia, and other countries. Linkage analysis in these consanguineous families showed homozygosity across the same region, leading to a maximum multipoint LOD score of 11.7 at theta=0 with D20S905. Six genes within the critical interval between D20S95 and D20S192 were sequenced. But, mutations were detected in only one of the six genes: FLJ20116, which was renamed as KIND1. The Omani family with two affected siblings was shown to have the 811C>T mutation in exon 6 of the KIND1 gene, predicting amino acid change R271X.
Ashton et al. (2004) identified a new mutation (c.1848G>A; p.W616X) in exon 14 of the KIND1 gene. This mutation was found in homozygous state in two female Omani patients (7 and 19-yrs old) from unrelated consanguineous families. Both patients presented with trauma induced blistering in childhood, photosensitivity, and poikiloderma, and were diagnosed with KS. In addition, the 19 years old patient also had dysphagia with esophageal stenosis and had a sibling who died in early infancy because of skin fragility and secondary infection. Haplotype analysis of the patient's DNA when compared to that of controls', showed that the W616X mutation occurred in both patients on a similar genetic background, consistent with the propagation of an ancestral founder allele in the Omani gene pool. Ashton et al. (2004) suggested using this phenomenon in mutation detection in patients of the same ethnic group. Immunofluorescence labeling with antikindlin 1 antibody in the patients showed complete absence of fluorescence. Ashton et al. (2004) emphasized the usefulness of this antibody as a diagnostic probe in KS.
Al Aboud et al. (2002) reported a large consanguineous Saudi Arabian family, in which 11 individuals in two sibships were affected with Kindler syndrome. Only eight of these patients were alive at the time of reporting. They presented with photosensitivity, generalized poikiloderma, webbed fingers, dermatogyphic loss, and nail dystrophy. Additionally, many of the patients had oral involvement, with gum bleeding. Some also had pseudoainhum of the toes, and sclerotic bands on the wrists. One year later, Al-Aboud et al. (2003) went on to describe some additional clinical features noticed in one of these patients, a 28-year old man, during follow-up. These features included patches of normal appearing skin, not involved by telangectases on the neck, and dorsum of both feet. Al-Aboud et al. (2003) hypothesized a case of revertant mosaicism giving rise to these normal patches of skin. In addition, a 4 cm circular patch of skin on the medial aspect of the left palm resembled the skin on the dorsum of the hand. Skin biopsy of this area revealed normal skin structure with hair follicles. Al-Aboud and colleagues (2003) were unable to explain this occurrence, but presumed that this was due to a disruption in the development of proper orientation during morphogenesis.
In the study conducted by Siegel et al. (2003) to identify the genetic basis of Kindler sydrome, at least one consanguineous family from Saudi Arabia was analyzed. In this family, the disease was linked to mutations in the KIND1 gene [See also: Oman > Siegel et al., 2003].
Jobard et al. (2003) included a Tunisian family in their study of Kindler syndrome. This consanguineous family had two affected children (a boy and a girl) in two sibships. Both patients presented with spontaneous blisters on the arms and legs, marked atrophic, wrinkled skin on the dorsa of the feet and hands, dyschromic patches with reticulated erythema and telangiectases, dysphagia, and esophageal stenosis. Epidermal atrophy and fibrosis of the papillary dermis were revealed in the skin biopsy, although the collagen and elastic fibers were found to be normal [See also > Algeria > Jobard et al., 2003].