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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Kindler Syndrome - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="Kindler Syndrome">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2022/01/06">
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<meta name="citation_author" content="Leila Youssefian">
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<meta name="citation_author" content="Hassan Vahidnezhad">
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<meta name="citation_author" content="Jouni Uitto">
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<meta name="citation_keywords" content="Congenital Bullous Poikiloderma">
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<meta name="citation_keywords" content="Congenital Bullous Poikiloderma">
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<meta name="citation_keywords" content="Fermitin family homolog 1">
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<meta name="citation_keywords" content="FERMT1">
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<meta name="citation_keywords" content="Kindler Syndrome">
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<meta name="DC.Title" content="Kindler Syndrome">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Leila Youssefian">
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<meta name="DC.Contributor" content="Hassan Vahidnezhad">
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<meta name="DC.Contributor" content="Jouni Uitto">
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<meta name="DC.Date" content="2022/01/06">
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<meta name="description" content="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.">
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<meta name="og:description" content="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.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK349072_"><span class="title" itemprop="name">Kindler Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Congenital Bullous Poikiloderma</div><p class="contribs">Youssefian L, Vahidnezhad H, Uitto J.</p><p class="fm-aai"><a href="#_NBK349072_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 23 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="kindler.Summary" itemprop="description"><h2 id="_kindler_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>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.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of KS is established in a proband with suggestive clinical findings and biallelic pathogenic variants in <i>FERMT1</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> 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.</p><p><i>Surveillance:</i> 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.</p><p><i>Agents/circumstances to avoid:</i> Sun exposure.</p><p><i>Pregnancy management:</i> Planning for potential complications at delivery (e.g., vaginal stenosis, labial synechiae). Breast-feeding is not advised due to risk of blistering breasts.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>KS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an <i>FERMT1</i> 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 <i>FERMT1</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.</p></div></div><div id="kindler.Diagnosis"><h2 id="_kindler_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for Kindler syndrome (KS) have been published.</p><div id="kindler.Suggestive_Findings"><h3>Suggestive Findings</h3><p>KS <b>should be suspected</b> in individuals with the following clinical findings, skin biopsy results, and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div><b>Skin fragility with trauma-induced blistering.</b> Blisters are present at birth and result from cutaneous trauma and/or exposure to sunlight.</div></li><li class="half_rhythm"><div><b>Skin atrophy.</b> Thin, wrinkled (cigarette-paper) skin, developing early in life, particularly present on the dorsa of the hands and feet</div></li><li class="half_rhythm"><div><b>Photosensitivity.</b> Erythema and burning within minutes of sun exposure; tends to improve with age.</div></li><li class="half_rhythm"><div><b>Poikiloderma.</b> Reticular telangiectasia and mottled hypo- and hyperpigmentation of the skin appear between ages two and three years.</div></li><li class="half_rhythm"><div><b>Hyperkeratosis of the palms and soles</b> with fissuring; a waxy appearance on the palms may be associated with the loss of the dermal ridges (i.e., fingerprints).</div></li><li class="half_rhythm"><div><b>Pseudosyndactyly</b> (i.e., partial fusion of the third and fourth and fourth and fifth toes) is associated with repeated blistering and scarring in infancy.</div></li><li class="half_rhythm"><div><b>Fragility of mucosal surfaces</b> including the conjunctiva, periodontal tissues, gastrointestinal tract, and/or external genitourinary structures</div></li></ul><p>
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<b>Skin biopsy results</b>
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</p><ul><li class="half_rhythm"><div><b>Histopathologic examination</b> shows hyperkeratosis, nonspecific epidermal atrophy, dermal edema, incontinence of pigment with or without cytoid bodies, loss of rete ridges, and focal vacuolization of the basal layer of the epidermis and pigmentary incontinence in the upper dermis, consistent with poikiloderma [<a class="bibr" href="#kindler.REF.shimizu.1997.1111" rid="kindler.REF.shimizu.1997.1111">Shimizu et al 1997</a>]. A characteristic feature is a split within the basement membrane zone at different levels. However, the most frequently encountered cleavage plane is through the lowermost portion of the basal layer of the epidermis. Extensive reduplication of the basement membrane and associated collagen deposition within the clefts are unique ultrastructural and histopathologic findings suggestive of KS.</div></li><li class="half_rhythm"><div><b>Electron microscopy.</b> The level of cleavage of blisters can be variable; intradermal, junctional, and dermal cleavage planes have been reported in a single biopsy from one individual.</div></li><li class="half_rhythm"><div><b>Transmission electron microscopy</b> of nonblistered skin demonstrates marked disorganization of the dermoepidermal basement membrane with reduplication of the basal lamina, focal interruptions of the lamina densa, and cleavage at or close to the dermoepidermal junction. Desmosomes, hemidesosomes, tonofilaments, anchoring filaments, and anchoring fibrils appear normal [<a class="bibr" href="#kindler.REF.shimizu.1997.1111" rid="kindler.REF.shimizu.1997.1111">Shimizu et al 1997</a>, <a class="bibr" href="#kindler.REF.lanschuetzer.2003.553" rid="kindler.REF.lanschuetzer.2003.553">Lanschuetzer et al 2003</a>].</div></li><li class="half_rhythm"><div><b>Immunofluorescence staining.</b> Antigen mapping analysis revealed that the major diagnostic criterion for KS is intense, broad, reticulate, and branching staining pattern with antibodies directed against laminin-332 and type IV and type VII collagen. Although anti-kindlin-1 immunostaining is also applied as a diagnostic test for KS, the final confirmation is made by <i>FERMT1</i> molecular genetic testing [<a class="bibr" href="#kindler.REF.lanschuetzer.2003.553" rid="kindler.REF.lanschuetzer.2003.553">Lanschuetzer et al 2003</a>, <a class="bibr" href="#kindler.REF.barzegar.2015.e416" rid="kindler.REF.barzegar.2015.e416">Barzegar et al 2015</a>].</div></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="kindler.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of KS <b>is established</b> in a proband with <a href="#kindler.Suggestive_Findings">suggestive clinical findings</a> and biallelic pathogenic (or likely pathogenic) variants in <i>FERMT1</i> identified by molecular genetic testing (see <a href="/books/NBK349072/table/kindler.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobkindlerTmoleculargenetictestingused">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#kindler.REF.richards.2015.405" rid="kindler.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>FERMT1</i> variants of uncertain significance (or of one known <i>FERMT1</i> pathogenic variant and one <i>FERMT1</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Because the phenotype of KS may be indistinguishable from many other inherited disorders with cutaneous fragility, recommended molecular genetic testing approaches include use of a <b>multigene panel</b> or <b>comprehensive genomic testing</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm">A <b>skin fragility multigene panel</b> that includes <i>FERMT1</i> and other genes of interest (see <a href="#kindler.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTmoleculargenetictestingused"><a href="/books/NBK349072/table/kindler.T.molecular_genetic_testing_used/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobkindlerTmoleculargenetictestingused"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.molecular_genetic_testing_used"><a href="/books/NBK349072/table/kindler.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobkindlerTmoleculargenetictestingused">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Kindler Syndrome </p></div></div></div></div><div id="kindler.Clinical_Characteristics"><h2 id="_kindler_Clinical_Characteristics_">Clinical Characteristics</h2><div id="kindler.Clinical_Description"><h3>Clinical Description</h3><p>Kindler syndrome (KS), a rare subtype of epidermolysis bullosa, is characterized by skin fragility and acral blister formation beginning at birth or in early infancy, diffuse cutaneous atrophy, photosensitivity (most prominent during childhood and usually decreasing after adolescence), poikiloderma, 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 include ectropion, urethral stenosis, and severe phimosis. Severe long-term complications of KS include periodontitis, mucosal strictures, and aggressive squamous cell carcinomas.</p><p>To date, about 400 individuals have been identified with biallelic pathogenic variants in <i>FERMT1</i> [<a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTkindlersyndromefrequencyof"><a href="/books/NBK349072/table/kindler.T.kindler_syndrome_frequency_of/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobkindlerTkindlersyndromefrequencyof"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.kindler_syndrome_frequency_of"><a href="/books/NBK349072/table/kindler.T.kindler_syndrome_frequency_of/?report=objectonly" target="object" rid-ob="figobkindlerTkindlersyndromefrequencyof">Table 2. </a></h4><p class="float-caption no_bottom_margin">Kindler Syndrome: Frequency of Select Features </p></div></div><p><b>The phenotypic spectrum</b> ranges from mild to severe based on age of onset, organs involved, and severity of manifestations. The mild end of the spectrum is characterized by minimal skin involvement (such as that observed in adults with KS), with or without other mild manifestations. Some individuals with mild manifestations are not diagnosed until late in life; for example, two individuals were diagnosed by molecular genetic testing in their 60s and 70s after early-stage cutaneous precancerous lesions and epithelial skin cancer were identified and treated in their 50s [<a class="bibr" href="#kindler.REF.has.2010.309" rid="kindler.REF.has.2010.309">Has et al 2010</a>]. In contrast, the severe end of the spectrum is characterized by such findings as severe mucosal involvement, severe esophageal stenosis, pseudoainhum, anemia, and/or malignancies.</p><p><b>Blisters</b> are present at birth; those observed in childhood are mainly localized to extremities.</p><ul><li class="half_rhythm"><div>Blisters result from trauma and/or exposure to sunlight.</div></li><li class="half_rhythm"><div>The number of blisters decreases by age ten to 12 years [<a class="bibr" href="#kindler.REF.siegel.2003.174" rid="kindler.REF.siegel.2003.174">Siegel et al 2003</a>, <a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>].</div></li><li class="half_rhythm"><div>Pyogenic skin infections can be a complication of blistering.</div></li></ul><p><b>Skin atrophy,</b> characterized by thin, wrinkled (cigarette-paper) skin is initially primarily localized to hands and feet; atrophy becomes generalized by adolescence and is often present on the abdomen, thighs, knees, and elbows (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1a</a>, <a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">1f</a>, <a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">1g</a>) [<a class="bibr" href="#kindler.REF.jobard.2003.925" rid="kindler.REF.jobard.2003.925">Jobard et al 2003</a>].</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figkindlerF1" co-legend-rid="figlgndkindlerF1"><a href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1"><img class="small-thumb" src="/books/NBK349072/bin/kindler-Image001.gif" src-large="/books/NBK349072/bin/kindler-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndkindlerF1"><h4 id="kindler.F1"><a href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-ob="figobkindlerF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Characteristic clinical features of Kindler syndrome a. Child age nine years: atrophy of skin on the dorsum of the hands and poikiloderma on the neck and axillary area</p></div></div><p><b>Photosensitivity,</b> characterized by erythema and burning after sun exposure, tends to improve with age; however, some degree of photosensitivity usually persists (e.g., facial erythema after minimal sun exposure) [<a class="bibr" href="#kindler.REF.ashton.2004.78" rid="kindler.REF.ashton.2004.78">Ashton et al 2004</a>]. Note: Affected individuals can develop redness within minutes of sun exposure.</p><p><b>Poikiloderma,</b> which is not present at birth, appears first on sun-exposed areas, progressing with age to non-sun-exposed areas (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1b</a>). This is characterized by reticular telangiectasia and mottled hypo- and hyperpigmentation of the skin, frequently appearing between ages two and three years. Generalized poikiloderma (in both sun-exposed and non-sun-exposed areas) eventually develops and persists throughout adult life in most affected individuals.</p><p>Axillary freckling may be observed in some (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1a</a>) [<a class="bibr" href="#kindler.REF.jobard.2003.925" rid="kindler.REF.jobard.2003.925">Jobard et al 2003</a>, <a class="bibr" href="#kindler.REF.siegel.2003.174" rid="kindler.REF.siegel.2003.174">Siegel et al 2003</a>, <a class="bibr" href="#kindler.REF.rayinda.2021.1343" rid="kindler.REF.rayinda.2021.1343">Rayinda et al 2021</a>].</p><p><b>Hyperkeratosis of the palms and soles</b> has been reported as fissured or punctate [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>] and is observed in about 65% of affected individuals. Palmar hyperkeratosis often has a waxy appearance, occasionally leading to the loss of the dermal ridges (i.e., fingerprints). Dermatoglyphics can be flattened or lost. Some individuals may have ridged, ribbed hyperkeratosis of the lateral and anterior ankles reminiscent of epidermolytic hyperkeratosis.</p><p><b>Pseudosyndactyly.</b> Typically, interdigital webbing develops (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1f</a>), but without the scarring or milia noted in other forms of epidermolysis bullosa (EB) [<a class="bibr" href="#kindler.REF.jobard.2003.925" rid="kindler.REF.jobard.2003.925">Jobard et al 2003</a>, <a class="bibr" href="#kindler.REF.siegel.2003.174" rid="kindler.REF.siegel.2003.174">Siegel et al 2003</a>].</p><p>Constricting bands of the pseudoainhum type have also been reported (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1e</a>, <a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">1g</a>) [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>].</p><p><b>Mucosal involvement</b> can include the following [<a class="bibr" href="#kindler.REF.jobard.2003.925" rid="kindler.REF.jobard.2003.925">Jobard et al 2003</a>, <a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>]:</p><ul><li class="half_rhythm"><div><b>Eyes.</b> Conjunctivitis, conjunctival scarring, corneal erosion, and ectropion of the lower eyelids [<a class="bibr" href="#kindler.REF.lelli.2010.368" rid="kindler.REF.lelli.2010.368">Lelli 2010</a>, <a class="bibr" href="#kindler.REF.martinez.2011" rid="kindler.REF.martinez.2011">Martinez & Siegel 2011</a>, <a class="bibr" href="#kindler.REF.signessoler.2013.e9" rid="kindler.REF.signessoler.2013.e9">Signes-Soler et al 2013</a>]</div></li><li class="half_rhythm"><div><b>Mouth and periodontium.</b> Severe periodontal disease (e.g., hemorrhagic mucositis, gingivitis, periodontitis, premature loss of teeth, and labial leukokeratosis), usually beginning in early adolescence [<a class="bibr" href="#kindler.REF.laicheong.2010.119" rid="kindler.REF.laicheong.2010.119">Lai-Cheong & McGrath 2010</a>]</div></li><li class="half_rhythm"><div><b>Gastrointestinal tract.</b> Esophageal stenosis, severe colitis, bloody diarrhea, constipation, and rectal mucosal fissures and stenosis. Affected children born with an imperforate anus that required surgical repair have also been reported [<a class="bibr" href="#kindler.REF.laicheong.2010.119" rid="kindler.REF.laicheong.2010.119">Lai-Cheong & McGrath 2010</a>].</div></li><li class="half_rhythm"><div>
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<b>Genitourinary tract</b>
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</div><ul><li class="half_rhythm"><div>Vaginal stenosis and labial synechiae</div></li><li class="half_rhythm"><div>Urethral meatal stenosis and urethral strictures, phimosis</div></li></ul></li></ul><p><b>Malignancy.</b> About half of individuals with KS will develop squamous cell carcinoma in their lifetime. An increased risk for malignancies has been reported:</p><ul><li class="half_rhythm"><div>Squamous cell carcinomas in acral skin and the mouth (lip and hard palate) [<a class="bibr" href="#kindler.REF.lotem.2001.1284" rid="kindler.REF.lotem.2001.1284">Lotem et al 2001</a>, <a class="bibr" href="#kindler.REF.emanuel.2006.305" rid="kindler.REF.emanuel.2006.305">Emanuel et al 2006</a>, <a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>]</div></li><li class="half_rhythm"><div>Transitional cell carcinomas of the bladder [<a class="bibr" href="#kindler.REF.alper.1978.457" rid="kindler.REF.alper.1978.457">Alper et al 1978</a>]</div></li></ul><p><b>Other findings</b> that may be present:</p><ul><li class="half_rhythm"><div>Xerosis, eczema, and dermatitis</div></li><li class="half_rhythm"><div>Variable hypermobility of the thumb, fingers, knees, and elbows without skin hyperextensibility [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>]</div></li><li class="half_rhythm"><div>Nail dystrophy (<a class="figpopup" href="/books/NBK349072/figure/kindler.F1/?report=objectonly" target="object" rid-figpopup="figkindlerF1" rid-ob="figobkindlerF1">Figure 1e</a>)</div></li></ul><p><b>Morbidity and mortality</b> mostly result from mucosal strictures and associated complications, secondary infections or cutaneous bullae, and cancer.</p></div><div id="kindler.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been identified.</p><p>Most <i>FERMT1</i> variants associated with Kindler syndrome are null variants. It has been proposed that <i>FERMT1</i> pathogenic missense variants and in-frame deletions are associated with milder disease manifestations and later onset of complications [<a class="bibr" href="#kindler.REF.maier.2016.920" rid="kindler.REF.maier.2016.920">Maier et al 2016</a>].</p></div><div id="kindler.Nomenclature"><h3>Nomenclature</h3><p>KS was first described by Theresa Kindler [<a class="bibr" href="#kindler.REF.kindler.1954.104" rid="kindler.REF.kindler.1954.104">Kindler 1954</a>].</p><p>In May 2007, 18 leading authorities on epidermolysis bullosa (EB) revised the EB classification to include KS based on its biologic and clinical findings [<a class="bibr" href="#kindler.REF.fine.2008.931" rid="kindler.REF.fine.2008.931">Fine et al 2008</a>, <a class="bibr" href="#kindler.REF.fine.2014.1103" rid="kindler.REF.fine.2014.1103">Fine et al 2014</a>].</p></div><div id="kindler.Prevalence"><h3>Prevalence</h3><p>Since the first description of KS in 1954 [<a class="bibr" href="#kindler.REF.kindler.1954.104" rid="kindler.REF.kindler.1954.104">Kindler 1954</a>], about 400 affected individuals have been reported worldwide.</p><p>Persons of any geographic origin can be affected and there is no sex predilection [<a class="bibr" href="#kindler.REF.siegel.2003.174" rid="kindler.REF.siegel.2003.174">Siegel et al 2003</a>, <a class="bibr" href="#kindler.REF.has.2011.1204" rid="kindler.REF.has.2011.1204">Has et al 2011</a>]. A cluster of 26 Panamanian affected individuals and 24 Iranian affected individuals with the syndrome have been identified [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>, <a class="bibr" href="#kindler.REF.youssefian.2015.1447" rid="kindler.REF.youssefian.2015.1447">Youssefian et al 2015</a>].</p></div></div><div id="kindler.Genetically_Related_Allelic_Diso"><h2 id="_kindler_Genetically_Related_Allelic_Diso_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>FERMT1</i>.</p></div><div id="kindler.Differential_Diagnosis"><h2 id="_kindler_Differential_Diagnosis_">Differential Diagnosis</h2><p>Before the onset of the photosensitivity and poikiloderma in the first few years of life, Kindler syndrome (KS) is frequently confused with other variants of epidermolysis bullosa (e.g., <a href="/books/n/gene/ebd/?report=reader">dystrophic</a>, <a href="/books/n/gene/ebj/?report=reader">junctional</a>, and <a href="/books/n/gene/ebs/?report=reader">simplex epidermolysis bullosa</a>); however, acral skin atrophy is indicative of KS. Furthermore, in contrast to blistering in other types of epidermolysis bullosa, the blistering in KS significantly improves with age.</p><p>Disorders of known genetic cause that can exhibit features of poikiloderma but are distinguishable by other clinical features are summarized <a href="/books/NBK349072/table/kindler.T.disorders_with_features_of_poi/?report=objectonly" target="object" rid-ob="figobkindlerTdisorderswithfeaturesofpoi">Table 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTdisorderswithfeaturesofpoi"><a href="/books/NBK349072/table/kindler.T.disorders_with_features_of_poi/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobkindlerTdisorderswithfeaturesofpoi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.disorders_with_features_of_poi"><a href="/books/NBK349072/table/kindler.T.disorders_with_features_of_poi/?report=objectonly" target="object" rid-ob="figobkindlerTdisorderswithfeaturesofpoi">Table 3. </a></h4><p class="float-caption no_bottom_margin">Disorders with Features of Poikiloderma in the Differential Diagnosis of Kindler Syndrome </p></div></div><p>
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<b>Disorders of unknown genetic cause with features of poikiloderma</b>
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</p><ul><li class="half_rhythm"><div>The designation <b>Weary-Kindler syndrome (WKS)</b> has been used for a disorder with features that overlap with KS including vesicopustules, eczema, poikiloderma, and acral keratotic papules in infancy. In WKS the bullae are not congenital and photosensitivity and mucosal involvement are not observed [<a class="bibr" href="#kindler.REF.weary.1971.409" rid="kindler.REF.weary.1971.409">Weary et al 1971</a>, <a class="bibr" href="#kindler.REF.larr_gue.1981.69" rid="kindler.REF.larr_gue.1981.69">Larrègue et al 1981</a>, <a class="bibr" href="#kindler.REF.laicheong.2009.233" rid="kindler.REF.laicheong.2009.233">Lai-Cheong et al 2009</a>]. It has been suggested that Weary and Kindler syndromes are aspects of the same disorder [<a class="bibr" href="#kindler.REF.lee.2012.225" rid="kindler.REF.lee.2012.225">Lee et al 2012</a>].</div></li><li class="half_rhythm"><div><b>Mendes da Costa syndrome</b>, also referred to as hereditary bullous dystrophy, macular type (OMIM <a href="https://omim.org/entry/302000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">302000</a>), is characterized by microcephaly, short stature, mild intellectual disability, cone-shaped fingers, and poikiloderma. The disorder has been described in Dutch and Italian families [<a class="bibr" href="#kindler.REF.sybert.2010" rid="kindler.REF.sybert.2010">Sybert 2010</a>].</div></li><li class="half_rhythm"><div><b>Hereditary sclerosing poikiloderma</b> (OMIM <a href="https://omim.org/entry/173700" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">173700</a>) is characterized by progressive poikiloderma in flexural areas (manifest as hyper- and hypopigmentation without telangiectasia or atrophy), sclerotic bands, poor dentition, and occasionally calcinosis cutis [<a class="bibr" href="#kindler.REF.weary.1969.413" rid="kindler.REF.weary.1969.413">Weary et al 1969</a>]. A later-onset complication is stenosis of cardiac valves. Absence of bullae and photosensitivity distinguish hereditary sclerosing poikiloderma from KS.</div></li></ul></div><div id="kindler.Management"><h2 id="_kindler_Management_">Management</h2><p>No clinical practice guidelines for Kindler syndrome (KS) have been published.</p><div id="kindler.Evaluation_Following_Initial_Dia"><h3>Evaluation Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with KS, the evaluations summarized in <a href="/books/NBK349072/table/kindler.T.recommended_evaluations_follow/?report=objectonly" target="object" rid-ob="figobkindlerTrecommendedevaluationsfollow">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTrecommendedevaluationsfollow"><a href="/books/NBK349072/table/kindler.T.recommended_evaluations_follow/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobkindlerTrecommendedevaluationsfollow"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.recommended_evaluations_follow"><a href="/books/NBK349072/table/kindler.T.recommended_evaluations_follow/?report=objectonly" target="object" rid-ob="figobkindlerTrecommendedevaluationsfollow">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Kindler Syndrome </p></div></div></div><div id="kindler.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>No established treatment for KS exists. The goals of care are to treat manifestations and prevent complications.</p><p>When possible, children with KS should be managed in a center experienced in caring for children with skin fragility by a multidisciplinary team that includes a dermatologist, pediatrician, ophthalmologist, dentist, gastroenterologist, urologist, nurse specialist, and dietitian.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTtreatmentofmanifestationsin"><a href="/books/NBK349072/table/kindler.T.treatment_of_manifestations_in/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobkindlerTtreatmentofmanifestationsin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.treatment_of_manifestations_in"><a href="/books/NBK349072/table/kindler.T.treatment_of_manifestations_in/?report=objectonly" target="object" rid-ob="figobkindlerTtreatmentofmanifestationsin">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Kindler Syndrome </p></div></div></div><div id="kindler.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTrecommendedsurveillancefori"><a href="/books/NBK349072/table/kindler.T.recommended_surveillance_for_i/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobkindlerTrecommendedsurveillancefori"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.recommended_surveillance_for_i"><a href="/books/NBK349072/table/kindler.T.recommended_surveillance_for_i/?report=objectonly" target="object" rid-ob="figobkindlerTrecommendedsurveillancefori">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Kindler Syndrome </p></div></div></div><div id="kindler.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid sun exposure by using sunscreen (SFP >30) and sun-protective clothing.</p></div><div id="kindler.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#kindler.Related_Genetic_Counseling_Issue">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="kindler.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Although the cutaneous manifestations of KS are not exacerbated by pregnancy, vaginal stenosis and labial synechiae have been reported; thus, obstetric planning, such as consideration of delivery by elective cesarean section, warrants consideration [<a class="bibr" href="#kindler.REF.mansur.2007.563" rid="kindler.REF.mansur.2007.563">Mansur et al 2007</a>]. Of note, specialized perioperative cesarean section management is needed to protect vulnerable skin and mucosa.</p><p>Breastfeeding is not advised because of the risk of blistering the breasts [<a class="bibr" href="#kindler.REF.hayashi.2007.72" rid="kindler.REF.hayashi.2007.72">Hayashi et al 2007</a>].</p></div><div id="kindler.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="kindler.Genetic_Counseling"><h2 id="_kindler_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="kindler.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Kindler syndrome (KS) is inherited in an autosomal recessive manner.</p></div><div id="kindler.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one <i>FERMT1</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm that both parents are heterozygous for an <i>FERMT1</i> pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#kindler.REF.j_nsson.2017.519" rid="kindler.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an <i>FERMT1</i> 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.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Unless an individual with KS has children with an affected individual or a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>FERMT1</i>.</div></li><li class="half_rhythm"><div>KS is reported more frequently in populations with high rates of consanguinity [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>, <a class="bibr" href="#kindler.REF.youssefian.2015.1447" rid="kindler.REF.youssefian.2015.1447">Youssefian et al 2015</a>]. Consanguinity increases the likelihood that an affected individual may have a reproductive partner who is heterozygous for an <i>FERMT1</i> pathogenic variant.</div></li><li class="half_rhythm"><div>The offspring of a proband and an individual heterozygous for an <i>FERMT1</i> pathogenic variant have a 50% chance of being affected and a 50% chance of being heterozygotes.</div></li></ul><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>FERMT1</i> pathogenic variant.</p></div><div id="kindler.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>FERMT1</i> pathogenic variants in the family.</p></div><div id="kindler.Related_Genetic_Counseling_Issue"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div><i>FERMT1</i> molecular genetic testing for reproductive partners of known carriers is appropriate, particularly if consanguinity is likely.</div></li></ul></div><div id="kindler.Prenatal_Testing_and_Preimplanta"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>FERMT1</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing for KS are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="kindler.Resources"><h2 id="_kindler_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>DEBRA</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 01344 771961</div><div><b>Email:</b> debra@debra.org.uk</div><div>
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<a href="https://www.debra.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">debra.org.uk</a>
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</div></li><li class="half_rhythm"><div>
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<b>DEBRA International</b>
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</div><div>
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<a href="https://www.debra-international.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">debra-international.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>debra of America</b>
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</div><div><b>Phone:</b> 833-debraUS</div><div><b>Email:</b> staff@debra.org</div><div>
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<a href="https://www.debra.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">debra.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Epidermolysis Bullosa Medical Research Foundation</b>
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</div><div><b>Phone:</b> 310-205-5119</div><div><b>Email:</b> a.pett@bep-la.com</div><div>
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<a href="https://www.ebmrf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EBMRF</a>
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</div></li><li class="half_rhythm"><div>
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<b>EBCare Registry</b>
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</div><div><b>Email:</b> connect@invitae.com</div><div>
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<a href="https://ebcare.patientcrossroads.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ebcare.patientcrossroads.org</a>
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</div></li></ul>
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</div><div id="kindler.Molecular_Genetics"><h2 id="_kindler_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlermolgenTA"><a href="/books/NBK349072/table/kindler.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobkindlermolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.molgen.TA"><a href="/books/NBK349072/table/kindler.molgen.TA/?report=objectonly" target="object" rid-ob="figobkindlermolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Kindler Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlermolgenTB"><a href="/books/NBK349072/table/kindler.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobkindlermolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.molgen.TB"><a href="/books/NBK349072/table/kindler.molgen.TB/?report=objectonly" target="object" rid-ob="figobkindlermolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Kindler Syndrome (View All in OMIM) </p></div></div><div id="kindler.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>FERMT1</i> is located on chromosome 20; it consists of 15 exons and encodes kindlin-1 protein with 677 amino acids (~77.4 kd). The gene is expressed in different tissues including skin keratinocytes and epithelial cells of colon, lung, placenta, adrenal, and prostate [<a class="bibr" href="#kindler.REF.jobard.2003.925" rid="kindler.REF.jobard.2003.925">Jobard et al 2003</a>]. Kindlin-1 is a focal adhesion protein that like other cytoskeletal proteins has "the four point one ezrin radixin and moesin" (FERM) and "pleckstrin" homology (PH) domains [<a class="bibr" href="#kindler.REF.larjava.2008.1203" rid="kindler.REF.larjava.2008.1203">Larjava et al 2008</a>]. Kindlin-1 is an adaptor protein that links filamentous actin in the cell to membrane proteins and is involved in integrin-associated signaling pathways [<a class="bibr" href="#kindler.REF.has.2011.1204" rid="kindler.REF.has.2011.1204">Has et al 2011</a>].</p><p>To date, a total of 91 loss-of-function pathogenic variants have been reported in <i>FERMT1</i>, including: missense, nonsense, and splicing variants; indels; and Alu-mediated gene rearrangements. The absence of kindlin-1 leads to disorganized keratinocytes as a result of aberrant integrin-mediated cell adhesion and migration [<a class="bibr" href="#kindler.REF.larjava.2008.1203" rid="kindler.REF.larjava.2008.1203">Larjava et al 2008</a>, <a class="bibr" href="#kindler.REF.rognoni.2016.17" rid="kindler.REF.rognoni.2016.17">Rognoni et al 2016</a>].</p><p><b>Mechanism of disease causation.</b> Kindler syndrome is thought to occur via a loss-of-function mechanism; pathogenic variants may lead to absent kindlin-1 protein or production of nonfunctional protein.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figkindlerTnotablefermt1pathogenicvari"><a href="/books/NBK349072/table/kindler.T.notable_fermt1_pathogenic_vari/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobkindlerTnotablefermt1pathogenicvari"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="kindler.T.notable_fermt1_pathogenic_vari"><a href="/books/NBK349072/table/kindler.T.notable_fermt1_pathogenic_vari/?report=objectonly" target="object" rid-ob="figobkindlerTnotablefermt1pathogenicvari">Table 7. </a></h4><p class="float-caption no_bottom_margin">Notable <i>FERMT1</i> Pathogenic Variants </p></div></div></div></div><div id="kindler.Chapter_Notes"><h2 id="_kindler_Chapter_Notes_">Chapter Notes</h2><div id="kindler.Author_Notes"><h3>Author Notes</h3><p><b>Jouni Uitto, MD, PhD</b> has been Professor of Dermatology and Cutaneous Biology, and Biochemistry and Molecular Biology, and Chair of the Department of Dermatology and Cutaneous Biology at The Sidney Kimmel Medical College at Thomas Jefferson University, in Philadelphia, Pennsylvania, since 1986. He is also Director of the Jefferson Institute of Molecular Medicine at Thomas Jefferson University. He received his MD and PhD degrees from the University of Helsinki, Finland, and completed his residency training in dermatology at Washington University School of Medicine, St. Louis, Missouri. Dr Uitto is internationally recognized for his research on connective tissue biology and molecular genetics in relation to cutaneous diseases. Dr Uitto's publications (as of November 2021) include 756 original articles in peer-reviewed journals, 364 text book chapters and review articles, and 1,057 abstracts on presentations in national and international meetings. Dr Uitto has been the recipient of numerous national and international awards, including honorary doctorate degrees from the University of Kuopio, University of Oulu, and University of Turku, all in Finland, as well as University of Buenos Aires, Argentina. He also has honorary professorships at China Medical University, Shenyang; Hebei United University, Tangshan; and The Fourth Military Medical University, Xi'an, all in China. Dr Uitto has held office in several scientific and professional societies, including as President of the Society for Investigative Dermatology, and President and Chair of the Board of Trustees of Dermatology Foundation. Dr Uitto is also Section Editor of the <i>Journal of Investigative Dermatology</i>, Associate Editor of the <i>American Journal of Pathology</i>, and he is on the editorial boards of numerous peer-reviewed journals.</p><p><b>Leila Youssefian, PhD</b> and <b>Hassan Vahidnezhad, PhD</b> are researchers in medical genetics working on genodermatoses at Jefferson Institute of Molecular Medicine of Thomas Jefferson University in Philadelphia, Pennsylvania.</p><p>Leila Youssefian and Hassan Vahidnezhad contributed equally to this work.</p><p>
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<b>DEBRA Molecular Diagnostics Laboratory</b>
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</p><p>Department of Dermatology and Cutaneous Biology<br />Thomas Jefferson University<br />233 South 10th Street<br />Bluemle Life Sciences Building, Suite 431<br />Philadelphia, PA, USA 19107<br /><b>Phone</b>: 215-503-5785</p><p>Individuals with Kindler syndrome, Kindler epidermolysis bullosa, or Kindler-like syndrome interested in receiving information and free genetic testing can contact Leila Youssefian (email: leila.youssefian@jefferson.edu or phone: 610-999-9402).</p></div><div id="kindler.Acknowledgments"><h3>Acknowledgments</h3><p>Carol Kelly assisted in manuscript preparation.</p></div><div id="kindler.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>6 January 2022 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>1 December 2016 (aa) Revision: addition to <a href="#kindler.Differential_Diagnosis">Differential Diagnosis</a></div></li><li class="half_rhythm"><div>3 March 2016 (bp) Review posted live</div></li><li class="half_rhythm"><div>3 August 2015 (ly) Original submission</div></li></ul></div></div><div id="kindler.References"><h2 id="_kindler_References_">References</h2><div id="kindler.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.alper.1978.457">Alper JC, Baden HP, Goldsmith LA. 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Inherited skin disorders presenting with poikiloderma. <span><span class="ref-journal">Int J Dermatol. </span>2021;<span class="ref-vol">60</span>:1343–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33739439" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33739439</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. 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The kindlin family: functions, signaling properties and implications for human disease. <span><span class="ref-journal">Journal of cell science. </span>2016;<span class="ref-vol">129</span>:17–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26729028" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26729028</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.sadler.2006.1619">Sadler E, Klausegger A, Muss W, Deinsberger U, Pohla-Gubo G, Laimer M, Lanschuetzer C, Bauer JW, Hintner H. Novel KIND1 gene mutation in Kindler syndrome with severe gastrointestinal tract involvement. <span><span class="ref-journal">Arch Dermatol. </span>2006;<span class="ref-vol">142</span>:1619–24.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17178989" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17178989</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.shimizu.1997.1111">Shimizu H, Sato M, Ban M, Kitajima Y, Ishizaki S, Harada T, Bruckner-Tuderman L, Fine JD, Burgeson R, Kon A, McGrath JA, Christiano AM, Uitto J, Nishikawa T. Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa. <span><span class="ref-journal">Arch Dermatol. </span>1997;<span class="ref-vol">133</span>:1111–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9301588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9301588</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.siegel.2003.174">Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, South AP, Smith FJ, Prescott AR, Wessagowit V, Oyama N, Akiyama M, Al Aboud D, Al Aboud K, Al Githami A, Al Hawsawi K, Al Ismaily A, Al-Suwaid R, Atherton DJ, Caputo R, Fine JD, Frieden IJ, Fuchs E, Haber RM, Harada T, Kitajima Y, Mallory SB, Ogawa H, Sahin S, Shimizu H, Suga Y, Tadini G, Tsuchiya K, Wiebe CB, Wojnarowska F, Zaghloul AB, Hamada T, Mallipeddi R, Eady RA, McLean WH, McGrath JA, Epstein EH. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2003;<span class="ref-vol">73</span>:174–87.</span> [<a href="/pmc/articles/PMC1180579/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1180579</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12789646" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12789646</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.signessoler.2013.e9">Signes-Soler I, Rodriguez-Prats JL, Carbonell S, Tañá-Rivero P. Corneal erosion and Kindler syndrome. <span><span class="ref-journal">Optom Vis Sci. </span>2013;<span class="ref-vol">90</span>:e9–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23241824" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23241824</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.sybert.2010">Sybert VP. <em>Genetic Skin Disorders</em>. 2 ed. Oxford, UK: Oxford University Press; 2010.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.techanukul.2011.267">Techanukul T, Sethuraman G, Zlotogorski A, Horev L, Macarov M, Trainer A, Fong K, Lens M, Medenica L, Ramesh V, McGrath JA, Lai-Cheong JE. Novel and recurrent FERMT1 gene mutations in Kindler syndrome. <span><span class="ref-journal">Acta Derm Venereol. </span>2011;<span class="ref-vol">91</span>:267–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21336475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21336475</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.vahidnezhad.2021.43">Vahidnezhad H, Youssefian L, Saeidian AH, Boyden LM, Touati A, Harvey N, Naji M, Zabihi M, Barzegar M, Sotoudeh S, Liu L, Guy A, Kariminejad A, Zeinali S, Choate KA, McGrath JA, Uitto J. Kindler epidermolysis bullosa-like skin phenotype and downregulated basement membrane zone gene expression in poikiloderma with neutropenia and a homozygous USB1 mutation. <span><span class="ref-journal">Matrix Biol. </span>2021;<span class="ref-vol">99</span>:43–57.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/34004352" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34004352</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.vahidnezhad.2018.22">Vahidnezhad H, Youssefian L, Saeidian AH, Mahmoudi H, Touati A, Abiri M, Kajbafzadeh AM, Aristodemou S, Liu L, McGrath JA, Ertel A, Londin E, Kariminejad A, Zeinali S, Fortina P, Uitto J. Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy. <span><span class="ref-journal">Matrix Biol. </span>2018;<span class="ref-vol">66</span>:22–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29138120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29138120</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.valinotto.2020.337">Valinotto LE, Natale MI, Lusso SB, Cella E, Gutiérrez O, Sebastiani F, Manzur GB. A novel pathogenic FERMT1 variant in four families with Kindler syndrome in Argentina. <span><span class="ref-journal">Pediatr Dermatol. </span>2020;<span class="ref-vol">37</span>:337–341.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31957900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31957900</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.weary.1969.413">Weary PE, Hsu YT, Richardson DR, Caravati CM, Wood BT. Hereditary sclerosing poikiloderma. Report of two families with an unusual and distinctive genodermatosis. <span><span class="ref-journal">Arch Dermatol. </span>1969;<span class="ref-vol">100</span>:413–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/5358102" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5358102</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.weary.1971.409">Weary PE, Manley WF Jr, Graham GF. Hereditary acrokeratotic poikiloderma. <span><span class="ref-journal">Arch Dermatol. </span>1971;<span class="ref-vol">103</span>:409–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/4253719" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4253719</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="kindler.REF.youssefian.2015.1447">Youssefian L, Vahidnezhad H, Barzegar M, Li Q, Sotoudeh S, Yazdanfar A, Ehsani AH, Kajbafzadeh AM, Mozafari N, Ebrahimi Daryani N, Agha-Hosseini F, Zeinali S, Uitto J. The Kindler syndrome: a spectrum of FERMT1 mutations in Iranian families. <span><span class="ref-journal">J Invest Dermatol. </span>2015;<span class="ref-vol">135</span>:1447–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25599393" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25599393</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK349072_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Leila Youssefian</span>, PhD<div class="affiliation small">Department of Dermatology and Cutaneous Biology<br />Sidney Kimmel Medical College<br />Thomas Jefferson University<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.nosreffej@naifessuoy.aliel" class="oemail">ude.nosreffej@naifessuoy.aliel</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Hassan Vahidnezhad</span>, PhD<div class="affiliation small">Department of Dermatology and Cutaneous Biology<br />Sidney Kimmel Medical College<br />Thomas Jefferson University<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.nosreffej@dahzendihav.nassah" class="oemail">ude.nosreffej@dahzendihav.nassah</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jouni Uitto</span>, MD, PhD<div class="affiliation small">Department of Dermatology and Cutaneous Biology<br />Sidney Kimmel Medical College<br />Thomas Jefferson University<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.nosreffej@ottiu.inuoj" class="oemail">ude.nosreffej@ottiu.inuoj</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">March 3, 2016</span>; Last Update: <span itemprop="dateModified">January 6, 2022</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Youssefian L, Vahidnezhad H, Uitto J. Kindler Syndrome. 2016 Mar 3 [Updated 2022 Jan 6]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/kos/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/kleefstra/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobkindlerTmoleculargenetictestingused"><div id="kindler.T.molecular_genetic_testing_used" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Kindler Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.molecular_genetic_testing_used/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.molecular_genetic_testing_used_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FERMT1</i>
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</td><td headers="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~95% <sup>4</sup></td></tr><tr><td headers="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_kindler.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~3% <sup>4</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="kindler.TF.1.1"><p class="no_margin">See <a href="/books/NBK349072/?report=reader#kindler.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="kindler.TF.1.2"><p class="no_margin">See <a href="#kindler.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="kindler.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="kindler.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#kindler.REF.stenson.2020.1197" rid="kindler.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="kindler.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobkindlerTkindlersyndromefrequencyof"><div id="kindler.T.kindler_syndrome_frequency_of" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Kindler Syndrome: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.kindler_syndrome_frequency_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.kindler_syndrome_frequency_of_lrgtbl__"><table><thead><tr><th id="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2" colspan="3" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Frequency</th></tr><tr><th headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2" id="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Nearly all</th><th headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2" id="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common</th><th headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2" id="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infrequent</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Blisters</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin atrophy</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Photosensitivity</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poikiloderma</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Axillary freckling</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperkeratosis of palms & soles</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pseudosyndactyly</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mucosal fragility</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Malignancy</td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_1_2 hd_h_kindler.T.kindler_syndrome_frequency_of_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobkindlerTdisorderswithfeaturesofpoi"><div id="kindler.T.disorders_with_features_of_poi" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Disorders with Features of Poikiloderma in the Differential Diagnosis of Kindler Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.disorders_with_features_of_poi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.disorders_with_features_of_poi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Characteristics</th></tr><tr><th headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4" id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Ectodermal Findings</th><th headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4" id="hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other Findings</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ACD</i>
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<br />
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<i>CTC1</i>
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<br />
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<i>DKC1</i>
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<br />
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<i>NHP2</i>
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<br />
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<i>NOP10</i>
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<br />
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<i>PARN</i>
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<br />
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<i>RTEL1</i>
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<br />
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<i>TERC</i>
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<br />
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<i>TERT</i>
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<br />
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<i>TINF2</i>
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<br />
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<i>WRAP53</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/dkc/?report=reader">Dyskeratosis congenita</a>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL<br />AD<br />AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dysplastic nails, lacy reticular pigmentation of upper chest &/or neck. Poikiloderma & nail dystrophy occur in late childhood.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Oral leukoplakia. ↑ risk for progressive bone marrow failure, myelodysplastic syndrome or acute myelogenous leukemia, solid tumors, & pulmonary fibrosis.</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ANAPC1</i>
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<br />
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<i>RECQL4</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/rts/?report=reader">Rothmund-Thomson syndrome</a>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rash that typically develops ages 3-6 mos (occasionally as late as age 2 yrs) as erythema, swelling, & blistering on face, then spreading to buttocks & extremities. Over mos to yrs, rash evolves into poikiloderma. Sparse hair, eyelashes, &/or eyebrows.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Small size; skeletal & dental abnormalities; juvenile cataracts; ↑ risk for cancer, esp osteosarcoma</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BLM</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/bloom/?report=reader">Bloom syndrome</a>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin at birth & during early infancy appears normal. During 1st or 2nd yr of life, typically following sun exposure, red, sun-sensitive rash appears on nose & cheeks (sometimes also on dorsa of hands & forearms). Rash varies in severity & extent & is usually characterized by telangiectasia but in others is described as poikiloderma.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe pre- & postnatal growth deficiency, highly characteristic sparseness of subcutaneous fat tissue throughout infancy & early childhood, & short stature throughout postnatal life. Gastroesophageal reflux is common.</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CD151</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">KS-like epidermolysis bullosa <sup>1</sup></td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Facial freckling, poikiloderma, atrophy of skin, & acrogeria of backs of hands on sun-exposed areas. Unlike KS, which presents w/blistering during childhood, 1 person described <sup>1</sup> presented widespread blistering & erosions primarily in pretibial area in adulthood. Dystrophic nails in all fingers & toes & early-onset alopecia were also observed.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The person described <sup>1</sup> had history of nephropathy manifesting w/proteinuria.</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DDB2</i>
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<br />
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<i>ERCC1</i>
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<br />
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<i>ERCC2</i>
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<br />
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<i>ERCC3</i>
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<br />
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<i>ERCC4</i>
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<br />
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<i>ERCC5</i>
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<br />
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<i>POLH</i>
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<br />
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<i>XPA</i>
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<br />
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<i>XPC</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/xp/?report=reader">Xeroderma pigmentosum</a> (XP)</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sun sensitivity w/marked freckle-like pigmentation of face before age 2 yrs. Sunlight-induced ocular involvement. Greatly ↑ risk of sunlight-induced cutaneous neoplasms. XP typically does not have acral bullae whereas in KS acral bullae are observed in childhood.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~25% of affected persons have neurologic manifestations.</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FAM111B</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hfpoik-tmp/?report=reader">Hereditary fibrosing poikiloderma w/tendon contractures, myopathy, & pulmonary fibrosis</a>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poikiloderma (typically beginning in 1st 6 mos & mainly localized to face), hypohidrosis w/heat intolerance, mild lymphedema of extremities, chronic erythematous & scaly skin lesions on extremities, sclerosis of digits, & mild palmoplantar keratoderma. Typically scalp hair, eyelashes, &/or eyebrows are sparse; nail dysplasia may be assoc.</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Muscle contractures usually seen in childhood; progressive weakness of proximal & distal muscles of all 4 limbs</td></tr><tr><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>USB1</i>
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</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/poikiloderma-n/?report=reader">Poikiloderma w/neutropenia</a> (Clericuzio-type poikiloderma w/neutropenia) <sup>2</sup></td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Inflammatory eczematous rash (ages 6-12 mos) followed by post-inflammatory poikiloderma (age >2 yrs); nail dystrophy & palmar/plantar hyperkeratosis</td><td headers="hd_h_kindler.T.disorders_with_features_of_poi_1_1_1_4 hd_h_kindler.T.disorders_with_features_of_poi_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chronic noncyclic neutropenia typically assoc w/recurrent sinopulmonary infections in 1st 2 yrs of life & (often) bronchiectasis. ↑ risk for myelodysplastic syndrome. Reactive airway disease.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; KS = Kindler syndrome; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="kindler.TF.3.1"><p class="no_margin">
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<a class="bibr" href="#kindler.REF.vahidnezhad.2018.22" rid="kindler.REF.vahidnezhad.2018.22">Vahidnezhad et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="kindler.TF.3.2"><p class="no_margin">
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<a class="bibr" href="#kindler.REF.vahidnezhad.2021.43" rid="kindler.REF.vahidnezhad.2021.43">Vahidnezhad et al [2021]</a>
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</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobkindlerTrecommendedevaluationsfollow"><div id="kindler.T.recommended_evaluations_follow" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Kindler Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.recommended_evaluations_follow/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.recommended_evaluations_follow_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin issues</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comprehensive dermatologic eval for skin fragility, blistering, photosensitivity, & risk for squamous cell carcinoma</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic consult for conjunctival involvement</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Mouth</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental consult for periodontal involvement</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>GI tract</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Gastroenterology eval for strictures affecting GI tract</div></li><li class="half_rhythm"><div>Incl eval of nutritional status, diet, & oral intake</div></li></ul>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genitourinary</b>
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<br />
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<b>tract</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Males: urology consult for urethra or foreskin stricture/stenosis</div></li><li class="half_rhythm"><div>Females: gynecology eval for vaginal or labial stricture/stenosis</div></li></ul>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
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<br />
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<b>counseling</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & families re nature, MOI, & implications of KS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#kindler.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
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</td><td headers="hd_h_kindler.T.recommended_evaluations_follow_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal; KS = Kindler syndrome; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="kindler.TF.4.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobkindlerTtreatmentofmanifestationsin"><div id="kindler.T.treatment_of_manifestations_in" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Kindler Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.treatment_of_manifestations_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.treatment_of_manifestations_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin blistering</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>If blister is not painful, it should be kept intact.</div></li><li class="half_rhythm"><div>Otherwise alleviate blister-related pain by draining fluid using a sterile needle, leaving overlying skin in place.</div></li><li class="half_rhythm"><div>Apply ointment to blister & cover w/nonstick gauze bandage.</div></li><li class="half_rhythm"><div>Antibiotics may be used to treat infected blister.</div></li></ul>
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</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin fragility</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Protection from trauma, e.g., by use of soft & protective clothing & avoiding contact sports to prevent physical trauma</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin atrophy</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Use of moisturizers for dry, pruritic skin</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Photosensitivity</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sun safety education, incl use of high sun-protective factor (>30 SPF) sunscreens, use of sun-protective clothing (hats & long-sleeve shirts), & avoidance of sun exposure as much as possible</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lubrication of cornea by artificial tears & eye drops</div></li><li class="half_rhythm"><div>Prevention of infections by use of local antibiotics</div></li><li class="half_rhythm"><div>Surgical correction of corneal scarring by ophthalmologist as needed</div></li></ul>
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</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Mouth &</b>
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<br />
|
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<b>periodontium</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Regular dental care to ensure optimal oral hygiene to reduce periodontal disease</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>GI tract</b>
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Esophageal dilation may be indicated for those w/dysphagia.</div></li><li class="half_rhythm"><div>Esophageal strictures & stenosis may require fluoroscopically guided balloon dilations [<a class="bibr" href="#kindler.REF.sadler.2006.1619" rid="kindler.REF.sadler.2006.1619">Sadler et al 2006</a>].</div></li><li class="half_rhythm"><div>Temporary parenteral nutrition may be necessary when esophageal dysfunction is severe.</div></li><li class="half_rhythm"><div>Anal stenosis & bleeding requires regular laxatives.</div></li><li class="half_rhythm"><div>Severe colitis may require surgical bowel resection in some cases.</div></li></ul>
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</td></tr><tr><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genitourinary</b>
|
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<br />
|
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<b>tract</b>
|
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</td><td headers="hd_h_kindler.T.treatment_of_manifestations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Urethral meatal stenosis may require dilation. Strictures may require stenting &/or surgical intervention.</div></li><li class="half_rhythm"><div>Most males require circumcision for phimosis.</div></li><li class="half_rhythm"><div>Vaginal or labial stricture/stenosis may require surgical intervention. In case of pregnancy, delivery should be considered by an elective cesarean section.</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobkindlerTrecommendedsurveillancefori"><div id="kindler.T.recommended_surveillance_for_i" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Kindler Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.recommended_surveillance_for_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.recommended_surveillance_for_i_lrgtbl__"><table><thead><tr><th id="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Risk for skin cancer</b>
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</td><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screen for premalignant keratoses & early squamous cell carcinomas.</td><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Starting in adolescence; annually thereafter</td></tr><tr><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Risk for oral mucosa tumors</b>
|
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</td><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screen for oral ulcerations, gingivitis, & periodontitis.</td><td headers="hd_h_kindler.T.recommended_surveillance_for_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Starting in adolescence & w/regular dental checkups</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobkindlermolgenTA"><div id="kindler.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Kindler Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_kindler.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_kindler.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_kindler.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_kindler.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_kindler.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_kindler.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_kindler.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/55612" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
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<i>FERMT1</i>
|
|
</a>
|
|
</td><td headers="hd_b_kindler.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=55612" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">20p12<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_kindler.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.uniprot.org/uniprot/Q9BQL6" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Fermitin family homolog 1</a>
|
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</td><td headers="hd_b_kindler.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://databases.lovd.nl/shared/genes/FERMT1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FERMT1 database</a>
|
|
</td><td headers="hd_b_kindler.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=FERMT1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FERMT1</a>
|
|
</td><td headers="hd_b_kindler.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=FERMT1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">FERMT1</a>
|
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="kindler.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobkindlermolgenTB"><div id="kindler.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Kindler Syndrome (<a href="/omim/173650,607900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/173650" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">173650</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">KINDLER SYNDROME; KNDLRS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/607900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">FERM DOMAIN-CONTAINING KINDLIN 1; FERMT1</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobkindlerTnotablefermt1pathogenicvari"><div id="kindler.T.notable_fermt1_pathogenic_vari" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Notable <i>FERMT1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK349072/table/kindler.T.notable_fermt1_pathogenic_vari/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__kindler.T.notable_fermt1_pathogenic_vari_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference<br />Sequences</th><th id="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_1" rowspan="7" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_017671.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_017671<wbr style="display:inline-block"></wbr>​.5</a>
|
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<br />
|
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_060141.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_060141<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.328C>T</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg110Ter</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.has.2010.309" rid="kindler.REF.has.2010.309">Has et al 2010</a>, <a class="bibr" href="#kindler.REF.almeida.2013.212" rid="kindler.REF.almeida.2013.212">Almeida et al 2013</a>, <a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.910G>T</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu304Ter</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.ashton.2004.78" rid="kindler.REF.ashton.2004.78">Ashton et al 2004</a>, <a class="bibr" href="#kindler.REF.sadler.2006.1619" rid="kindler.REF.sadler.2006.1619">Sadler et al 2006</a>, <a class="bibr" href="#kindler.REF.techanukul.2011.267" rid="kindler.REF.techanukul.2011.267">Techanukul et al 2011</a>, <a class="bibr" href="#kindler.REF.youssefian.2015.1447" rid="kindler.REF.youssefian.2015.1447">Youssefian et al 2015</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.676dupC</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln226fsTer16</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.martignago.2007.1281" rid="kindler.REF.martignago.2007.1281">Martignago et al 2007</a>, <a class="bibr" href="#kindler.REF.kiritsi.2012.1742" rid="kindler.REF.kiritsi.2012.1742">Kiritsi et al 2012</a>, <a class="bibr" href="#kindler.REF.almeida.2013.212" rid="kindler.REF.almeida.2013.212">Almeida et al 2013</a>, <a class="bibr" href="#kindler.REF.heidari.2016.403" rid="kindler.REF.heidari.2016.403">Heidari et al 2016</a>, <a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>, <a class="bibr" href="#kindler.REF.valinotto.2020.337" rid="kindler.REF.valinotto.2020.337">Valinotto et al 2020</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.862C>T</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg288Ter</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.siegel.2003.174" rid="kindler.REF.siegel.2003.174">Siegel et al 2003</a>, <a class="bibr" href="#kindler.REF.krishna.2014.340" rid="kindler.REF.krishna.2014.340">Krishna et al 2014</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.676C>T</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln226Ter</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.heidari.2016.403" rid="kindler.REF.heidari.2016.403">Heidari et al 2016</a>, <a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.456dupA</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asp153fs</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.kiritsi.2012.1742" rid="kindler.REF.kiritsi.2012.1742">Kiritsi et al 2012</a>, <a class="bibr" href="#kindler.REF.guerreroaspizua.2019.183" rid="kindler.REF.guerreroaspizua.2019.183">Guerrero-Aspizua et al 2019</a>]</td></tr><tr><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.811C>T</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg271Ter</td><td headers="hd_h_kindler.T.notable_fermt1_pathogenic_vari_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common pathogenic variant [<a class="bibr" href="#kindler.REF.penagos.2004.939" rid="kindler.REF.penagos.2004.939">Penagos et al 2004</a>, <a class="bibr" href="#kindler.REF.burch.2006.620" rid="kindler.REF.burch.2006.620">Burch et al 2006</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobkindlerF1"><div id="kindler.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK349072/bin/kindler-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Characteristic clinical features of Kindler syndrome</p><p>a. Child age nine years: atrophy of skin on the dorsum of the hands and poikiloderma on the neck and axillary area</p><p>b. Poikiloderma of the neck</p><p>c. Urethral stenosis</p><p>d. Gingival fragility and enamel hypoplasia (arrows)</p><p>e. Individual age 35 years: atrophy of the skin on the dorsum of the feet, nail dystrophy, and bilateral pseudoainhum (acquired constricting ring around a digit) of fifth toes (arrow heads)</p><p>f. Cutaneous atrophy with calcinosis cutis of the dorsum of the hands and pseudosyndactyly</p><p>g. Pseudoainhum in the fifth finger (arrow head)</p></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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