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<meta name="citation_date" content="2021/04/01">
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<meta name="citation_author" content="V Reid Sutton">
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<meta name="citation_keywords" content="Limb-Mammary Syndrome">
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<meta name="citation_keywords" content="Acro-Dermo-Ungual-Lacrimal-Tooth Syndrome (ADULT Syndrome)">
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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="_NBK43797_"><span class="title" itemprop="name"><i>TP63</i>-Related Disorders</span></h1><p class="contribs">Sutton VR, van Bokhoven H.</p><p class="fm-aai"><a href="#_NBK43797_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 27 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="aec.Summary" itemprop="description"><h2 id="_aec_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>The <i>TP63</i>-related disorders comprise six overlapping phenotypes:</p><ul><li class="half_rhythm"><div>Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome)</div></li><li class="half_rhythm"><div>Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome</div></li><li class="half_rhythm"><div>Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3)</div></li><li class="half_rhythm"><div>Limb-mammary syndrome</div></li><li class="half_rhythm"><div>Split-hand/foot malformation type 4 (SHFM4)</div></li><li class="half_rhythm"><div>Isolated cleft lip/cleft palate (orofacial cleft 8)</div></li></ul><p>Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of a <i>TP63</i>-related disorder is established in a proband with suggestive findings and a heterozygous pathogenic variant in <i>TP63</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> A multidisciplinary team of specialists in clinical genetics, dermatology, ophthalmology, otolaryngology, audiology, dentistry and prosthodontics, plastic surgery, nutrition/gastroenterology, and psychology is recommended. Skin erosions are treated with gentle wound care and periodic, dilute bleach soaks to prevent secondary infection, and infants with severe skin erosions are monitored and treated aggressively for dehydration, electrolyte imbalances, malnutrition, and infection. Wigs can be used for sparse hair and alopecia; dentures may be considered in early childhood and dental implants in the teens or early adulthood. Cleft lip/palate is managed per routine protocols; limb malformations are treated with occupational therapy and surgery as needed to optimize function.</p><p><i>Surveillance:</i> Regular attention to dental needs and possible hearing loss.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>The <i>TP63</i>-related disorders are inherited in an autosomal dominant manner. Approximately 30% of individuals diagnosed with a <i>TP63</i>-related disorder have an affected parent. The proportion of individuals with a <i>TP63</i>-related disorder caused by a <i>de novo</i>
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<i>TP63</i> pathogenic variant is approximately 70%. If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs is 50%. Once the <i>TP63</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p></div></div><div id="aec.GeneReview_Scope"><h2 id="_aec_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTc"><a href="/books/NBK43797/table/aec.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobaecTc"><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="aec.Tc"><a href="/books/NBK43797/table/aec.Tc/?report=objectonly" target="object" rid-ob="figobaecTc">Table</a></h4><p class="float-caption no_bottom_margin">Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome) Rapp-Hodgkin syndrome</p></div></div></div><div id="aec.Diagnosis"><h2 id="_aec_Diagnosis_">Diagnosis</h2><div id="aec.Suggestive_Findings"><h3>Suggestive Findings</h3><p>A <i>TP63</i>-related disorder <b>should be suspected/considered</b> in individuals with a combination of the following findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Ankyloblepharon filiforme adnatum</div></li><li class="half_rhythm"><div>Dermal erosions</div></li><li class="half_rhythm"><div>Signs of ectodermal dysplasia</div><ul><li class="half_rhythm"><div>Hypohidrosis</div></li><li class="half_rhythm"><div>Nail dysplasia</div></li><li class="half_rhythm"><div>Sparse hair</div></li><li class="half_rhythm"><div>Tooth abnormalities</div></li></ul></li><li class="half_rhythm"><div>Freckles in sun-exposed areas</div></li><li class="half_rhythm"><div>Cleft lip/palate</div></li><li class="half_rhythm"><div>Split-hand/foot malformation and/or syndactyly</div></li><li class="half_rhythm"><div>Lacrimal duct obstruction</div></li><li class="half_rhythm"><div>Hypopigmentation</div></li><li class="half_rhythm"><div>Hypospadias</div></li><li class="half_rhythm"><div>Hypoplastic nipples/breasts</div></li></ul><p><b>Family history</b> is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis.</p><p>Note: The <i>TP63</i>-related disorders include five overlapping phenotypes as well as isolated cleft lip/palate (see <a href="#aec.Clinical_Description">Clinical Description</a> and <a href="/books/NBK43797/table/aec.T.tp63related_disorders_comparison_o/?report=objectonly" target="object" rid-ob="figobaecTtp63relateddisorderscomparisono">Table 2</a> for details on the phenotypes).</p></div><div id="aec.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of a <i>TP63</i>-related disorder <b>is established</b> in a proband with <a href="#aec.Suggestive_Findings">suggestive findings</a> and a heterozygous pathogenic variant in <i>TP63</i> identified by molecular genetic testing (see <a href="/books/NBK43797/table/aec.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobaecTmoleculargenetictestingusedin">Table 1</a>). Identification of a heterozygous <i>TP63</i> variant of uncertain significance does not establish or rule out the diagnosis of this disorder.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing and multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#aec.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#aec.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other inherited disorders with ectodermal dysplasia, cleft lip/palate, or split-hand/foot malformation are more likely to be diagnosed using genomic testing (see <a href="#aec.Option_2">Option 2</a>).</p><div id="aec.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>TP63</i> is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</p><p><b>A multigene panel</b> that includes <i>TP63</i> and other genes of interest (see <a href="#aec.Differential_Diagnosis">Differential Diagnosis</a>) is more 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.</p><p>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>.</p></div><div id="aec.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>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.</p><p>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>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTmoleculargenetictestingusedin"><a href="/books/NBK43797/table/aec.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobaecTmoleculargenetictestingusedin"><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="aec.T.molecular_genetic_testing_used_in"><a href="/books/NBK43797/table/aec.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobaecTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>TP63</i>-Related Disorders </p></div></div></div></div></div><div id="aec.Clinical_Characteristics"><h2 id="_aec_Clinical_Characteristics_">Clinical Characteristics</h2><div id="aec.Clinical_Description"><h3>Clinical Description</h3><p>The <i>TP63</i>-related disorders include the overlapping phenotypes summarized in <a href="/books/NBK43797/table/aec.T.tp63related_disorders_comparison_o/?report=objectonly" target="object" rid-ob="figobaecTtp63relateddisorderscomparisono">Table 2</a> and fully described in the text that follows.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTtp63relateddisorderscomparisono"><a href="/books/NBK43797/table/aec.T.tp63related_disorders_comparison_o/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobaecTtp63relateddisorderscomparisono"><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="aec.T.tp63related_disorders_comparison_o"><a href="/books/NBK43797/table/aec.T.tp63related_disorders_comparison_o/?report=objectonly" target="object" rid-ob="figobaecTtp63relateddisorderscomparisono">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>TP63</i>-Related Disorders: Comparison of Phenotypes by Select Features </p></div></div><div id="aec.AEC_Syndrome"><h4>AEC Syndrome</h4><p>The manifestations of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome are typically present at birth.</p><p><b>Ankyloblepharon</b> is present in 70% of neonates. While the upper- and lower-eyelid adhesions can be obvious, partial adhesion of the upper and lower eyelids can be subtle and the filiform adhesions can spontaneously lyse before they are recognized as such.</p><p>Lacrimal puncta are frequently absent, often leading to chronic conjunctivitis and blepharitis, which is often not recognized in infancy but seen in early childhood [<a class="bibr" href="#aec.REF.sutton.2009.1916" rid="aec.REF.sutton.2009.1916">Sutton et al 2009</a>].</p><p>
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<b>Ectodermal defects</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Skin.</b> Nearly 100% of affected neonates have superficial skin erosions that vary from very limited to severe, life-threatening full-body involvement. The erosions most typically affect the scalp at birth and during infancy. Severe scalp erosions often lead to scarring alopecia and hypotrichosis. This is NOT seen in other <i>TP63-</i>related disorders.</div><div class="half_rhythm">The skin erosions tend to be recurrent and intermittent throughout childhood and into adulthood with frequent involvement of the head and neck, palms, soles, and skin folds.</div><div class="half_rhythm">Congenital erythroderma (i.e., diffuse erythema with associated erosions) is observed in 70%-90% of infants. The skin can also appear shiny with a collodion membrane (red, shiny, membranous skin changes) [<a class="bibr" href="#aec.REF.siegfried.2005.1591" rid="aec.REF.siegfried.2005.1591">Siegfried et al 2005</a>].</div><div class="half_rhythm">Children typically manifest cutaneous depigmentation and scarring, most likely due to postinflammatory pigmentary changes related to previous erythroderma and associated underlying erosions that may or may not be appreciated clinically. African American infants can have facial hypopigmentation in a mask pattern that improves with age. Affected individuals with fair skin typically have a reticulated hyperpigmentation on the neck and intertriginous areas that progresses with age to cribriform, reticulate, stellate, or punctate scarring most commonly on the shoulders, upper back, and chest.</div><div class="half_rhythm">Histopathologic features of skin biopsies may reveal epidermal atrophy, pigment incontinence, and a prominent superficial perivascular plexus with limited lymphocytic infiltrate [<a class="bibr" href="#aec.REF.dishop.2009.1935" rid="aec.REF.dishop.2009.1935">Dishop et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Hair changes</b> become more obvious with age. Hair is typically light colored and coarse, wiry, and brittle with a spun-glass/gold or "uncombable" appearance. Eyebrows and eyelashes are sparse. Light and scanning microscopy may reveal structural and pigmentary alterations of the hair including kinking, grooves, and discontinuous pigmentation.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Nail</b>
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<b>changes</b>, present in all and more obvious with age, vary among individuals. Most affected individuals have nail dystrophy (abnormal nail plate texture) and hyperconvex nail plates. Micronychia (abnormally small nail plates), distal frayed edges with nail plate resorption, and absent nails are also frequent [<a class="bibr" href="#aec.REF.julapalli.2009.1900" rid="aec.REF.julapalli.2009.1900">Julapalli et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Dental anomalies.</b> Malformed teeth (conical shape with small occlusal tables) and hypodontia (reduced number of teeth) also become evident during childhood and adolescence. Affected adults have an average of 4.75 secondary teeth [<a class="bibr" href="#aec.REF.farrington.2009.1907" rid="aec.REF.farrington.2009.1907">Farrington & Lausten 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Sweating.</b> In certain cases, there are fewer sweat pores and decreased sweating [<a class="bibr" href="#aec.REF.ferstl.2018.1727" rid="aec.REF.ferstl.2018.1727">Ferstl et al 2018</a>]; however, this does NOT lead to hyperthermia or fevers as seen in <a href="/books/n/gene/x-hed/?report=reader">hypohidrotic ectodermal dysplasia</a>.</div></li></ul><p><b>Clefting</b> is present in all. Clefting can include submucous cleft palate only, cleft of the soft and/or the hard palate only, cleft lip only, or the combination of cleft lip and cleft palate [<a class="bibr" href="#aec.REF.cole.2009.1910" rid="aec.REF.cole.2009.1910">Cole et al 2009</a>].</p><p><b>Other</b> findings include the following:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Limb anomalies</b> were initially not considered to be part of the syndrome, but syndactyly of fingers and toes and/or camptodactyly (permanent and irreducible flexion of the fingers) of hands have been seen. Split-hand/foot malformation was observed in two of 17 individuals (12%) with AEC syndrome [<a class="bibr" href="#aec.REF.sutton.2009.1916" rid="aec.REF.sutton.2009.1916">Sutton et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Hypospadias</b> has been reported in 78% of males with AEC syndrome [<a class="bibr" href="#aec.REF.sutton.2009.1916" rid="aec.REF.sutton.2009.1916">Sutton et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Facial features</b> become more distinctive with age. Findings commonly include maxillary hypoplasia, micrognathia, broad nasal root, underdeveloped alae nasi, thin vermilion of the upper lip, and short philtrum.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Trismus</b> has been reported in 35% of individuals with AEC syndrome [<a class="bibr" href="#aec.REF.sutton.2009.1916" rid="aec.REF.sutton.2009.1916">Sutton et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Hearing loss.</b> More than 90% of children have conductive hearing loss, often with secondary speech delay [<a class="bibr" href="#aec.REF.cole.2009.1910" rid="aec.REF.cole.2009.1910">Cole et al 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Growth.</b> Poor weight gain and failure to thrive should be anticipated. When treated appropriately with nutritional supplementation poor weight gain improves with age.</div><div class="half_rhythm">Linear growth abnormalities are observed in early childhood with a significantly lower height for age compared to the reference population. The growth pattern in AEC is similar to that reported for hypohidrotic ectodermal dysplasia [<a class="bibr" href="#aec.REF.motil.2009.1922" rid="aec.REF.motil.2009.1922">Motil & Fete 2009</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Psychological impact</b> related to the phenotypic features of the disease can include a reduced quality of life with negative impact on both child and family. In one study, a variable degree of psychological functioning was noted with some families reporting few ill effects from the disease while others reported significant impact [<a class="bibr" href="#aec.REF.lane.2009.1926" rid="aec.REF.lane.2009.1926">Lane et al 2009</a>].</div></li></ul></div><div id="aec.ADULT_Syndrome"><h4>ADULT Syndrome</h4><p>The manifestations of acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome are typically present at birth (although they may become more prominent with age), with the exception of skin freckling.</p><p><b>Limb anomalies.</b> Syndactyly of fingers and toes is most commonly seen.</p><p>
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<b>Ectodermal defects</b>
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</p><ul><li class="half_rhythm"><div><b>Skin</b> tends to be dry but erosions are not present.</div></li><li class="half_rhythm"><div><b>Hair changes</b> are more obvious with age. Hair is typically light colored and fine. Eyebrows and eyelashes are sparse.</div></li><li class="half_rhythm"><div><b>Nail dysplasia</b> is commonly reported.</div></li><li class="half_rhythm"><div><b>Dental anomalies.</b> Malformed teeth (conical shape with small occlusal tables) and hypodontia (reduced number of teeth) also become evident during childhood and adolescence.</div></li><li class="half_rhythm"><div><b>Sweating.</b> Subjective decreased sweat production is universal and is reported as heat intolerance; however, this does NOT lead to hyperthermia or fevers as seen in <a href="/books/n/gene/x-hed/?report=reader">hypohidrotic ectodermal dysplasia</a>.</div></li></ul><p><b>Lacrimal duct atresia</b> is frequent and often leads to chronic conjunctivitis and blepharitis, which are often not recognized until early childhood [<a class="bibr" href="#aec.REF.sutton.2009.1916" rid="aec.REF.sutton.2009.1916">Sutton et al 2009</a>].</p><p><b>Breast and/or nipple hypoplasia</b> is seen commonly and most notably in females. This feature is characteristic of ADULT and limb-mammary syndrome and NOT typically seen in other <i>TP63-</i>related disorders.</p><p><b>Excessive freckling</b> in sun-exposed areas is seen in a subset of affected individuals and progresses with age and sun exposure. This feature is NOT seen in other <i>TP63-</i>related disorders.</p></div><div id="aec.EEC3"><h4>EEC3</h4><p>The manifestations of ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3) are typically present at birth.</p><p><b>Limb anomalies</b> are seen in 68%-90% of individuals with 60% having tetramelic involvement. A wide variety of limb abnormalities are reported including syndactyly, oligodactyly, split-hand/foot malformation, and digital duplication. A cohort of 152 individuals with EEC syndrome showed split-hand/foot malformation in 68% and syndactyly in 43% [<a class="bibr" href="#aec.REF.rinne.2006a.1396" rid="aec.REF.rinne.2006a.1396">Rinne et al 2006a</a>].</p><p>
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<b>Ectodermal defects</b>
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</p><ul><li class="half_rhythm"><div><b>Skin</b> tends to be dry but erosions are not present.</div></li><li class="half_rhythm"><div><b>Hair changes</b> become more obvious with age and are seen in 60%-80% of individuals with EEC syndrome [<a class="bibr" href="#aec.REF.rinne.2006a.1396" rid="aec.REF.rinne.2006a.1396">Rinne et al 2006a</a>]. Hair is typically silvery blond, coarse, and dry; 20% have sparse hair. Light microscopy has been reported to be normal in EEC syndrome [<a class="bibr" href="#aec.REF.pashayan.1974.105" rid="aec.REF.pashayan.1974.105">Pashayan et al 1974</a>]. Eyebrows and eyelashes are sparse.</div></li><li class="half_rhythm"><div><b>Nail</b>
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<b>dysplasia</b> is commonly reported.</div></li><li class="half_rhythm"><div><b>Dental anomalies.</b> Malformed teeth (conical shape with small occlusal tables) and hypodontia (reduced number of teeth) also become evident during childhood and adolescence.</div></li><li class="half_rhythm"><div><b>Sweating.</b> Hypohidrosis is uncommon in EEC3 [<a class="bibr" href="#aec.REF.ferstl.2018.1727" rid="aec.REF.ferstl.2018.1727">Ferstl et al 2018</a>].</div></li></ul><p><b>Cleft lip with or without cleft palate</b> is present in 60%-75% and is bilateral in half of cases. Clefting can include submucous cleft palate only, cleft of the soft and/or the hard palate only, cleft lip only, or the combination of cleft lip and cleft palate [<a class="bibr" href="#aec.REF.buss.1995.716" rid="aec.REF.buss.1995.716">Buss et al 1995</a>].</p><p><b>Absent lacrimal puncta</b> is reported in 90% of individuals and results in tearing, blepharitis, dacryocystitis, keratoconjunctivitis, and photophobia and often leads to corneal ulceration and scarring [<a class="bibr" href="#aec.REF.buss.1995.716" rid="aec.REF.buss.1995.716">Buss et al 1995</a>].</p><p><b>Genitourinary malformations</b> are reported in 45% and may include hypospadias and developmental abnormalities of the kidneys and urinary collecting system.</p></div><div id="aec.LimbMammary_Syndrome"><h4>Limb-Mammary Syndrome</h4><p>The manifestations of limb-mammary syndrome are typically present at birth.</p><p><b>Limb anomalies</b> including split-hand/foot malformation and syndactyly are reported in 75%-85% of individuals.</p><p><b>Breast and/or nipple hypoplasia</b> is seen commonly with almost all individuals having nipple aplasia or hypoplasia and 90% of females having mammary gland aplasia or hypoplasia. This feature is characteristic of ADULT and limb-mammary syndrome and NOT typically seen in other <i>TP63-</i>related disorders.</p><p><b>Lacrimal duct atresia</b> is seen in about half leading to chronic conjunctivitis and blepharitis, which are often not recognized until early childhood [<a class="bibr" href="#aec.REF.van_bokhoven.1999.538" rid="aec.REF.van_bokhoven.1999.538">van Bokhoven et al 1999</a>].</p><p>
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<b>Ectodermal defects</b>
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</p><ul><li class="half_rhythm"><div><b>Nail</b>
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<b>dysplasia</b> is reported in 30% of individuals.</div></li><li class="half_rhythm"><div><b>Dental anomalies.</b> Hypodontia (reduced number of teeth) also becomes evident during childhood and adolescence and is seen in 10%-15%.</div></li></ul><p>Note: Skin and hair abnormalities are NOT typically seen, in contrast to other <i>TP63-</i>related disorders.</p><p><b>Cleft lip with or without cleft palate</b> is present in 25%-30% of individuals and can include submucous cleft palate only, cleft of the soft and/or the hard palate only, cleft lip only, or the combination of cleft lip and cleft palate.</p></div><div id="aec.SHFM4"><h4>SHFM4</h4><p>The manifestations of split-hand/foot malformation-4 (SHFM4) are typically present at birth.</p><p><b>Limb abnormalities</b> include median clefts of the hands and feet; aplasia/hypoplasia of phalanges, metacarpals, and metatarsals; and some syndactyly.</p><p><b>Ectodermal abnormalities and cleft lip/palate</b> are considered to be exclusion criteria for making the diagnosis SHFM4.</p></div><div id="aec.Isolated_Cleft_LipPalate_Orofacial_C"><h4>Isolated Cleft Lip/Palate (Orofacial Cleft 8)</h4><p>Identification of a <i>TP63</i> pathogenic variant in three individuals ‒ a girl age 4 years; a boy age 3 years and his father; all with apparent nonsyndromic cleft lip/palate ‒ have been reported by <a class="bibr" href="#aec.REF.leoyklang.2006.e28" rid="aec.REF.leoyklang.2006.e28">Leoyklang et al [2006]</a> and <a class="bibr" href="#aec.REF.basha.2018.449" rid="aec.REF.basha.2018.449">Basha et al [2018]</a>, respectively. Further evaluations revealed no other features of <i>TP63-</i>related disorders in these individuals.</p><p><a class="bibr" href="#aec.REF.khandelwal.2019.1101" rid="aec.REF.khandelwal.2019.1101">Khandelwal et al [2019]</a> identified partial deletions of <i>TP63</i> in individuals from three families with orofacial cleft and/or hypodontia and minor anomalies of the skin and nails.</p></div></div><div id="aec.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Note: Pathogenic variants have been described on two <i>TP63</i> isoforms: the TAp63α isoform, encoded by <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_003722.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_003722.4</a>, and the ΔNp63α isoform, encoded by <a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001114982.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001114982.1</a>, which is 39 amino acids shorter and has an alternate N-terminal TA domain. See <a class="figpopup" href="/books/NBK43797/figure/aec.F1/?report=objectonly" target="object" rid-figpopup="figaecF1" rid-ob="figobaecF1">Figure 1</a> for details.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figaecF1" co-legend-rid="figlgndaecF1"><a href="/books/NBK43797/figure/aec.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figaecF1" rid-ob="figobaecF1"><img class="small-thumb" src="/books/NBK43797/bin/aec-Image001.gif" src-large="/books/NBK43797/bin/aec-Image001.jpg" alt="Figure 1. . Typical and common TP63 pathogenic variants identified in various disorders as indicated by color key." /></a><div class="icnblk_cntnt" id="figlgndaecF1"><h4 id="aec.F1"><a href="/books/NBK43797/figure/aec.F1/?report=objectonly" target="object" rid-ob="figobaecF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Typical and common <i>TP63</i> pathogenic variants identified in various disorders as indicated by color key. Pathogenic variants indicated by * are specific for the ΔNp63α isoform and their numbering is based on the respective reference sequences <a href="/books/NBK43797/figure/aec.F1/?report=objectonly" target="object" rid-ob="figobaecF1">(more...)</a></p></div></div><p><b>AEC syndrome.</b> All pathogenic variants associated with AEC syndrome occur in either the sterile alpha motif (SAM) domain (82%) or the ΔNp63-specific N-terminal domain (18%). Pathogenic variants in the N-terminal domain that introduce premature termination codons lead to the use of an alternative start codon [<a class="bibr" href="#aec.REF.rinne.2008.1968" rid="aec.REF.rinne.2008.1968">Rinne et al 2008</a>] and to the consequent production of ΔNp63α isoforms lacking the N-terminal domain, which are specifically associated with AEC syndrome. This isoform of p63 is the predominant isoform in mature epidermis, and it has been shown to repress ZNF750, leading to impaired epidermal differentiation [<a class="bibr" href="#aec.REF.zarnegar.2012.435" rid="aec.REF.zarnegar.2012.435">Zarnegar et al 2012</a>].</p><p><b>ADULT syndrome</b> is typically associated with pathogenic variants in the DNA binding domain. Other pathogenic variants have been reported in isolated individuals with features reminiscent of ADULT syndrome, but also of other <i>TP63</i>-associated syndromes in ΔNp63α (an alternative TA domain), in TAp63α between the TA and DNA binding domains [<a class="bibr" href="#aec.REF.rinne.2006b.904" rid="aec.REF.rinne.2006b.904">Rinne et al 2006b</a>, <a class="bibr" href="#aec.REF.rinne.2007.262" rid="aec.REF.rinne.2007.262">Rinne et al 2007</a>], and at other locations in TAp63α [<a class="bibr" href="#aec.REF.van_zelststams.2009.1558" rid="aec.REF.van_zelststams.2009.1558">van Zelst-Stams & van Steensel 2009</a>].</p><p><b>EEC3.</b> All EEC3-causing pathogenic variants are missense variants in the DNA binding domain and have been demonstrated to disrupt DNA binding [<a class="bibr" href="#aec.REF.rinne.2006b.904" rid="aec.REF.rinne.2006b.904">Rinne et al 2006b</a>]. Splice changes and frameshifts associated with EEC3 have been reported [<a class="bibr" href="#aec.REF.celli.1999.143" rid="aec.REF.celli.1999.143">Celli et al 1999</a>, <a class="bibr" href="#aec.REF.van_bokhoven.2001.481" rid="aec.REF.van_bokhoven.2001.481">van Bokhoven et al 2001</a>, <a class="bibr" href="#aec.REF.barrow.2002.559" rid="aec.REF.barrow.2002.559">Barrow et al 2002</a>, <a class="bibr" href="#aec.REF.monti.2013.894" rid="aec.REF.monti.2013.894">Monti et al 2013</a>].</p><p><b>Limb-mammary syndrome</b> is caused by pathogenic missense variants that are located between the transactivation domain and the DNA binding domain (p.Gly115, p.Ser129, and p.Gly173 residues in TAp63α) or by truncating variants in the SAM domain of <i>TP63</i> [<a class="bibr" href="#aec.REF.van_bokhoven.2001.481" rid="aec.REF.van_bokhoven.2001.481">van Bokhoven et al 2001</a>, <a class="bibr" href="#aec.REF.rinne.2007.262" rid="aec.REF.rinne.2007.262">Rinne et al 2007</a>].</p><p><b>SHFM4.</b> Pathogenic missense variants in the TA and DNA binding domains have been associated with SHFM4 [<a class="bibr" href="#aec.REF.rinne.2007.262" rid="aec.REF.rinne.2007.262">Rinne et al 2007</a>].</p><p><b>Orofacial cleft 8</b> has been associated with a <i>TP63</i> variant in the DNA binding domain [<a class="bibr" href="#aec.REF.leoyklang.2006.e28" rid="aec.REF.leoyklang.2006.e28">Leoyklang et al 2006</a>, <a class="bibr" href="#aec.REF.basha.2018.449" rid="aec.REF.basha.2018.449">Basha et al 2018</a>].</p></div><div id="aec.Penetrance"><h3>Penetrance</h3><p>Reduced penetrance or possible germline mosaicism has been documented in a small number of individuals and families.</p><ul><li class="half_rhythm"><div class="half_rhythm">Reduced penetrance for SHFM4 [<a class="bibr" href="#aec.REF.spranger.1988.202" rid="aec.REF.spranger.1988.202">Spranger & Schapera 1988</a>] and ADULT syndrome [<a class="bibr" href="#aec.REF.amiel.2001.642" rid="aec.REF.amiel.2001.642">Amiel et al 2001</a>] has been reported.</div></li><li class="half_rhythm"><div class="half_rhythm">A few individuals who do not appear to be clinically affected have had more than one child with AEC syndrome. These occurrences may be the result of reduced penetrance, but are more likely the result of somatic and germline mosaicism in one parent.</div><div class="half_rhythm">In one family, the <i>TP63</i> pathogenic variant present in affected fraternal twins was also present in the phenotypically normal mother. The data suggested somatic mosaicism in the mother [van Bokhoven, unpublished data] with presumed germline mosaicism.</div></li></ul></div><div id="aec.Nomenclature"><h3>Nomenclature</h3><p>Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is also known as Hay-Wells syndrome, after the physicians who first described the condition in 1976.</p><p>Rapp-Hodgkin syndrome (RHS), once considered a separate entity, is now considered to be part of the spectrum of the AEC syndrome because of the overlap of clinical manifestations and <i>TP63</i> pathogenic variants in the two conditions [<a class="bibr" href="#aec.REF.cambiaghi.1994.97" rid="aec.REF.cambiaghi.1994.97">Cambiaghi et al 1994</a>, <a class="bibr" href="#aec.REF.mcgrath.2001.221" rid="aec.REF.mcgrath.2001.221">McGrath et al 2001</a>].</p><p>EEC3 is thought to be genetically unrelated to EEC1 (which has been mapped to chromosome 7q11q21). An entity called EEC2 was initially mapped to chromosome 19 [<a class="bibr" href="#aec.REF.oquinn.1998.130" rid="aec.REF.oquinn.1998.130">O'Quinn et al 1998</a>]; however, pathogenic variants in <i>TP63</i> were ultimately identified [<a class="bibr" href="#aec.REF.celli.1999.143" rid="aec.REF.celli.1999.143">Celli et al 1999</a>].</p></div><div id="aec.Prevalence"><h3>Prevalence</h3><p><i>TP63-</i>related disorders are rare. The prevalence of disorders individually or collectively is unknown.</p></div></div><div id="aec.Genetically_Related_Allelic_Disorder"><h2 id="_aec_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with a heterozygous germline pathogenic variant in <i>TP63</i>.</p></div><div id="aec.Differential_Diagnosis"><h2 id="_aec_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTgenesofinterestinthedifferent"><a href="/books/NBK43797/table/aec.T.genes_of_interest_in_the_different/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobaecTgenesofinterestinthedifferent"><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="aec.T.genes_of_interest_in_the_different"><a href="/books/NBK43797/table/aec.T.genes_of_interest_in_the_different/?report=objectonly" target="object" rid-ob="figobaecTgenesofinterestinthedifferent">Table 3. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of <i>TP63</i>-Related Disorders </p></div></div><p>
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<b>Hereditary disorders of unknown genetic cause to consider in the differential diagnosis of <i>TP63</i>-related disorders</b>
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</p><ul><li class="half_rhythm"><div><b>Differential diagnosis of ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome (EEC).</b> EEC1 (OMIM <a href="https://omim.org/entry/129900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">129900</a>) is suspected to be caused by pathogenic variants in a gene on chromosome 7q21-q22 based on a series of individuals with various cytogenetically visible chromosomal abnormalities. Other EEC-like phenotypes that do not appear to involve the EEC1 and EEC3 loci have been described.</div></li><li class="half_rhythm"><div><b>Differential diagnosis of split-hand/foot malformation type 4 (SHFM4).</b> SHFM2 (OMIM <a href="https://omim.org/entry/313350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">313350</a>) has been mapped to Xq26, and while both males and females are affected, males tend to have a more severe phenotype. Cleft lip/palate and ectodermal defects are not seen in this condition.</div></li></ul></div><div id="aec.Management"><h2 id="_aec_Management_">Management</h2><p>No clinical practice guidelines for <i>TP63</i>-related disorders have been published.</p><div id="aec.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a <i>TP63</i> -related disorder, the evaluations summarized in <a href="/books/NBK43797/table/aec.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobaecTrecommendedevaluationsfollowing">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="figaecTrecommendedevaluationsfollowing"><a href="/books/NBK43797/table/aec.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobaecTrecommendedevaluationsfollowing"><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="aec.T.recommended_evaluations_following"><a href="/books/NBK43797/table/aec.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobaecTrecommendedevaluationsfollowing">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with a <i>TP63</i>-Related Disorder </p></div></div></div><div id="aec.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Management by multidisciplinary specialists, including clinical genetics, dermatology, ophthalmology, otolaryngology, audiology, dentistry and prosthodontics, plastic surgery, nutrition/gastroenterology, and psychology, is recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTtreatmentofmanifestationsinind"><a href="/books/NBK43797/table/aec.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobaecTtreatmentofmanifestationsinind"><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="aec.T.treatment_of_manifestations_in_ind"><a href="/books/NBK43797/table/aec.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figobaecTtreatmentofmanifestationsinind">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with a <i>TP63</i>-Related Disorder </p></div></div></div><div id="aec.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecTrecommendedsurveillanceforindiv"><a href="/books/NBK43797/table/aec.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobaecTrecommendedsurveillanceforindiv"><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="aec.T.recommended_surveillance_for_indiv"><a href="/books/NBK43797/table/aec.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" rid-ob="figobaecTrecommendedsurveillanceforindiv">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with a <i>TP63</i>-Related Disorder </p></div></div></div><div id="aec.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Prolonged exposure to sunlight should be avoided to:</p><ul><li class="half_rhythm"><div>Prevent sunburn of hypopigmented areas and increase in contrast between the patchy areas of hyper- and hypopigmentation seen in AEC syndrome;</div></li><li class="half_rhythm"><div>Minimize freckling of skin in individuals with ADULT syndrome.</div></li></ul></div><div id="aec.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic at-risk relatives in order to identify as early as possible those who would benefit from regular evaluation for disease manifestations with attention to dental needs and possible hearing loss.</p><p>See <a href="#aec.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="aec.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="aec.Genetic_Counseling"><h2 id="_aec_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="aec.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>TP63</i>-related disorders are inherited in an autosomal dominant manner.</p></div><div id="aec.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>Approximately 30% of individuals diagnosed with AEC have an affected parent. This appears to be true for the other <i>TP63</i>-related disorders as well [H van Bokhoven, AF Bree, VR Sutton, unpublished data].</div></li><li class="half_rhythm"><div>The proportion of individuals with AEC caused by a <i>de novo</i>
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<i>TP63</i> pathogenic variant is approximately 70%. This appears to be true for the other <i>TP63</i>-related disorders as well [H van Bokhoven, AF Bree, VR Sutton, unpublished data].</div></li><li class="half_rhythm"><div>If the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div class="half_rhythm">The proband has a <i>de novo</i> pathogenic variant. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bibr" href="#aec.REF.richards.2015.405" rid="aec.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism * [<a class="bibr" href="#aec.REF.enriquez.2016.2372" rid="aec.REF.enriquez.2016.2372">Enriquez et al 2016</a>; van Bokhoven, unpublished data]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism.</div><div class="half_rhythm">* A parent with somatic and germline mosaicism for a <i>TP63</i> pathogenic variant may be mildly/minimally affected.</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with a <i>TP63</i>-related disorder may appear to be negative because of failure to recognize the disorder in family members or reduced penetrance. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the <i>TP63</i> pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs is 50%. There can be a significant range of clinical variability in affected family members.</div></li><li class="half_rhythm"><div>If the <i>TP63</i> pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism [<a class="bibr" href="#aec.REF.enriquez.2016.2372" rid="aec.REF.enriquez.2016.2372">Enriquez et al 2016</a>; van Bokhoven, unpublished data].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>TP63</i> pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for a <i>TP63</i>-related disorder because of the possibility of reduced penetrance in a heterozygous parent or the possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with a <i>TP63</i>-related disorder has a 50% chance of inheriting the <i>TP63</i> pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the genetic status of the proband's parents: if a parent has the <i>TP63</i> pathogenic variant, his or her family members may be at risk.</p></div><div id="aec.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#aec.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><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 or at risk.</div></li></ul></div><div id="aec.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>TP63</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing 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="aec.Resources"><h2 id="_aec_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>National Foundation for Ectodermal Dysplasias (NFED)</b>
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</div><div><b>Phone:</b> 618-566-2020</div><div><b>Email:</b> info@nfed.org</div><div>
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<a href="http://www.nfed.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.nfed.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>American Cleft Palate-Craniofacial Association</b>
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</div><div><b>Phone:</b> 919-933-9044</div><div>
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<a href="https://acpa-cpf.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">acpa-cpf.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Children's Craniofacial Association</b>
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</div><div><b>Phone:</b> 800-535-3643</div><div><b>Email:</b> contactCCA@ccakids.com</div><div>
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<a href="https://ccakids.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ccakids.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Ectodermal Dysplasia Society</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 01242 261332</div><div><b>Email:</b> info@edsociety.co.uk</div><div>
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<a href="https://edsociety.co.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.edsociety.co.uk</a>
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</div></li><li class="half_rhythm"><div>
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<b>Face Equality International</b>
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</div><div>United Kingdom</div><div>
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<a href="https://faceequalityinternational.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">faceequalityinternational.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Library of Medicine Genetics Home Reference</b>
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</div><div>
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<a href="http://ghr.nlm.nih.gov/condition/ankyloblepharon-ectodermal-defects-cleft-lip-palate-syndrome" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome</a>
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</div></li><li class="half_rhythm"><div>
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<b>Selbsthilfegruppe Ektodermale Dysplasie e.V.</b>
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</div><div>
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<i>Consumer health-oriented organization for Germany, Austria, and Switzerland</i>
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</div><div>Germany</div><div><b>Phone:</b> 7127 969691</div><div><b>Email:</b> andrea@ektodermale-dysplasie.de</div><div>
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<a href="http://www.ektodermale-dysplasie.de" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ektodermale-dysplasie.de</a>
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</div></li><li class="half_rhythm"><div>
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<b>Ectodermal Dysplasias International Registry</b>
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</div><div><b>Email:</b> info@nfed.org</div><div>
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<a href="https://nfed.patientcrossroads.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Ectodermal Dysplasias International Registry</a>
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</div></li></ul>
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</div><div id="aec.Molecular_Genetics"><h2 id="_aec_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="figaecmolgenTA"><a href="/books/NBK43797/table/aec.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobaecmolgenTA"><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="aec.molgen.TA"><a href="/books/NBK43797/table/aec.molgen.TA/?report=objectonly" target="object" rid-ob="figobaecmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">TP63-Related Disorders: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figaecmolgenTB"><a href="/books/NBK43797/table/aec.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobaecmolgenTB"><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="aec.molgen.TB"><a href="/books/NBK43797/table/aec.molgen.TB/?report=objectonly" target="object" rid-ob="figobaecmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for TP63-Related Disorders (View All in OMIM) </p></div></div><div id="aec.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Transcription factor p63 encoded by <i>TP63</i> is a key regulator in epithelial commitment and development. <i>TP63</i> encodes a large number of p63 isoforms, which are engaged in dimeric and tetrameric complexes regulating a network of genes important for development of ectodermal structures [<a class="bibr" href="#aec.REF.khandelwal.2019.1101" rid="aec.REF.khandelwal.2019.1101">Khandelwal et al 2019</a>]. Different p63 isoforms have been shown to play roles in various cells and tissues, such as the epidermis, oocytes, muscles, and cochlea. TP63 is a master regulator of the embryonic development and differentiation of ectodermal cells [<a class="bibr" href="#aec.REF.shalomfeuerstein.2013.2152" rid="aec.REF.shalomfeuerstein.2013.2152">Shalom-Feuerstein et al 2013</a>]. Additionally, it plays a critical role in the development of the apical ectodermal ridge of the limb bud in collaboration with the signaling molecule FGF8 [<a class="bibr" href="#aec.REF.restelli.2014.3830" rid="aec.REF.restelli.2014.3830">Restelli et al 2014</a>]. The ΔN promoter is the only active promoter and the 3′ exon is the first expressed exon detected in epidermal cells throughout epidermal stratification in many epithelial cells, such as those from skin, oral tissues, and the mammary gland [<a class="bibr" href="#aec.REF.sethi.2015.584" rid="aec.REF.sethi.2015.584">Sethi et al 2015</a>, <a class="bibr" href="#aec.REF.soares.2018.1179" rid="aec.REF.soares.2018.1179">Soares & Zhou 2018</a>]. In contrast, the TA isoform is generally expressed at a low level in a range of nonepithelial cells. Thus, TAp63 is expressed in oocytes and plays an important role in controlling apoptosis in response to DNA damage [<a class="bibr" href="#aec.REF.deutsch.2011.566" rid="aec.REF.deutsch.2011.566">Deutsch et al 2011</a>]. In the cochlea, the TA isoform is also expressed and regulates the Notch signaling pathway, which is required for proper cochlea development [<a class="bibr" href="#aec.REF.terrinoni.2013.7300" rid="aec.REF.terrinoni.2013.7300">Terrinoni et al 2013</a>]. Additionally, TAp63 has been found to be expressed in late-stage myogenesis [<a class="bibr" href="#aec.REF.cefal_.2015.894" rid="aec.REF.cefal_.2015.894">Cefalù et al 2015</a>] and in cardiomyocyte development [<a class="bibr" href="#aec.REF.rouleau.2011.1672" rid="aec.REF.rouleau.2011.1672">Rouleau et al 2011</a>].</p><p><b>Mechanism of disease causation.</b> Variants in <i>TP63</i> lead to three major phenotypes: ectodermal dysplasia, orofacial clefting (OFC), and split-hand/foot malformation (SHFM) [<a class="bibr" href="#aec.REF.celli.1999.143" rid="aec.REF.celli.1999.143">Celli et al 1999</a>]. Heterozygous <i>TP63</i> variants have been associated with five different syndromes with overlapping phenotypic features: ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome (EEC), ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, Rapp-Hodgkin syndrome (RHS), acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome, and limb-mammary syndrome (LMS). Rare <i>TP63</i> variants are causative for OFC with variable mild ectodermal features (OFC8) [<a class="bibr" href="#aec.REF.leoyklang.2006.e28" rid="aec.REF.leoyklang.2006.e28">Leoyklang et al 2006</a>], and for nonsyndromic SHFM4.</p><p>A broad spectrum of different heterozygous variants has been reported in <i>TP63</i>, leading to the developmental disorders stated above. The vast majority of variants give rise to amino acid substitutions. A striking genotype-phenotype correlation for <i>TP63</i> missense variants is apparent in EEC and AEC syndrome / RHS [<a class="bibr" href="#aec.REF.rinne.2006a.1396" rid="aec.REF.rinne.2006a.1396">Rinne et al 2006a</a>, Figure 1]. Variants underlying EEC and AEC syndrome / RHS exert dominant-negative effects by interfering with normal p63 proteins in dimeric and tetrameric complexes. Variants in LMS affect yet another region of the p63 protein, and probably have dominant-negative effects. Causative variants in ADULT syndrome typically give rise to amino acid substitution of arginine 337 in the DNA-binding domain (DBD) but appear to exert gain-of-function effects, in contrast to dominant-negative DBD missense variants seen in EEC syndrome. Deletions encompassing large parts of <i>TP63</i> generating loss-of-function alleles are associated with OFC8 [<a class="bibr" href="#aec.REF.khandelwal.2019.1101" rid="aec.REF.khandelwal.2019.1101">Khandelwal et al 2019</a>].</p><p><b>Notable <i>TP63</i> variants.</b>
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<a class="figpopup" href="/books/NBK43797/figure/aec.F1/?report=objectonly" target="object" rid-figpopup="figaecF1" rid-ob="figobaecF1">Figure 1</a> demonstrates typical and common <i>TP63</i> pathogenic variants identified with the various phenotypes.</p></div></div><div id="aec.Chapter_Notes"><h2 id="_aec_Chapter_Notes_">Chapter Notes</h2><div id="aec.Author_Notes"><h3>Author Notes</h3><p>
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<a href="https://www.bcm.edu/people-search/vernon-sutton-31476" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Dr Sutton's web page</a>
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</p><p>
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<a href="https://www.radboudumc.nl/en/people/hans-van-bokhoven" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Dr van Bokhoven's web page</a>
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</p></div><div id="aec.Acknowledgments"><h3>Acknowledgments</h3><p>The authors would like to thank the National Foundation for Ectodermal Dysplasias and Executive Director Mary Fete, who organized the International Research Symposium on AEC syndrome, and all the individuals and families who participated in the research that contributed to this review. Additionally, we would like to express our gratitude to Dr John Carey and the <i>American Journal of Medical Genetics</i> for publishing these research results in a unified special issue of the journal.</p></div><div id="aec.Author_History"><h3>Author History</h3><p>Alanna F Bree, MD; Dermatology Specialists of Houston (2010-2015)<br />V Reid Sutton, MD (2010-present)<br />Hans van Bokhoven, PhD (2010-present)</p></div><div id="aec.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>1 April 2021 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 December 2019 (vrs) Revision: correction to SHFM4</div></li><li class="half_rhythm"><div>6 August 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>8 June 2010 (me) Review posted live</div></li><li class="half_rhythm"><div>2 February 2010 (vrs) Original submission</div></li></ul></div></div><div id="aec.References"><h2 id="_aec_References_">References</h2><div id="aec.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.amiel.2001.642">Amiel J, Bougeard G, Francannet C, Raclin V, Munnich A, Lyonnet S, Frebourg T. TP63 gene mutation in ADULT syndrome. <span><span class="ref-journal">Eur J Hum Genet. </span>2001;<span class="ref-vol">9</span>:642–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11528512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11528512</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.aradhya.2012.594">Aradhya S, Lewis R, Bonaga T, Nwokekeh N, Stafford A, Boggs B, Hruska K, Smaoul N, Compton JG, Richard G, Suchy S. Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders. <span><span class="ref-journal">Genet Med. </span>2012;<span class="ref-vol">14</span>:594–603.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22382802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22382802</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.barrow.2002.559">Barrow LL, van Bokhoven H, Daack-Hirsch S, Andersen T, van Beersum SE, Gorlin R, Murray JC. Analysis of the p63 gene in classical EEC syndrome, related syndromes, and non-syndromic orofacial clefts. <span><span class="ref-journal">J Med Genet. </span>2002;<span class="ref-vol">39</span>:559–66.</span> [<a href="/pmc/articles/PMC1735218/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735218</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12161593" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12161593</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.basha.2018.449">Basha M, Demeer B, Revencu N, Helaers R, Theys S, Bou Saba S, Boute O, Devauchelle B, Francois G, Bayet B, Vikkula M. Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes. <span><span class="ref-journal">J Med Genet. </span>2018;<span class="ref-vol">55</span>:449–58.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29500247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29500247</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.buss.1995.716">Buss PW, Hughes HE, Clarke A. Twenty-four cases of the EEC syndrome: clinical presentation and management. <span><span class="ref-journal">J Med Genet. </span>1995;<span class="ref-vol">32</span>:716–23.</span> [<a href="/pmc/articles/PMC1051673/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1051673</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8544192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8544192</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.cadieuxdion.2018.41">Cadieux-Dion M, Safina NP, Engleman K, Saunders C, Repnikova E, Raje N, Canty K, Farrow E, Miller N, Zellmer L, Thiffault I. Novel heterozygous pathogenic variants in CHUK in a patient with AEC-like phenotype, immune deficiencies and 1q21.1 microdeletion syndrome: a case report. <span><span class="ref-journal">BMC Med Genet. </span>2018;<span class="ref-vol">19</span>:41.</span> [<a href="/pmc/articles/PMC5845372/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5845372</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29523099" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29523099</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.cambiaghi.1994.97">Cambiaghi S, Tadini G, Barbareschi M, Menni S, Caputo R. Rapp-Hodgkin syndrome and AEC syndrome: Are they the same entity? <span><span class="ref-journal">Br J Dermatol. </span>1994;<span class="ref-vol">130</span>:97–101.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8305327" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8305327</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.cefal_.2015.894">Cefalù S, Lena AM, Vojtesek B, Musarò A, Rossi A, Melino G, Candi E. Tap63gamma is required for the late stages of myogenesis. <span><span class="ref-journal">Cell Cycle. </span>2015;<span class="ref-vol">14</span>:894–901.</span> [<a href="/pmc/articles/PMC4615066/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4615066</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25790093" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25790093</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.celli.1999.143">Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, Van Buggenhout G, van Haeringen A, Woods CG, van Essen AJ, de Waal R, Vriend G, Haber DA, Yang A, McKeon F, Brunner HG, van Bokhoven H. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. <span><span class="ref-journal">Cell. </span>1999;<span class="ref-vol">99</span>:143–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10535733" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10535733</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.cole.2009.1910">Cole P, Hatef DA, Kaufman Y, Magruder A, Bree A, Friedman E, Sindwani R, Hollier LH Jr. Facial clefting and oroauditory pathway manifestations in ankyloblepharon-ectodermal defects-cleft lip/palate syndrome. <span><span class="ref-journal">Am J Med Genet. </span>2009;<span class="ref-vol">149A</span>:1910–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19697430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19697430</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.de_mollerat.2003.1959">de Mollerat XJ, Gurrieri F, Morgan CT, Sangiorgi E, Everman DB, Gaspari P, Amiel J, Bamshad MJ, Lyle R, Blouin JL, Allanson JE, Le Marec B, Wilson M, Braverman NE, Radhakrishna U, Delozier-Blanchet C, Abbott A, Elghouzzi V, Antonarakis S, Stevenson RE, Munnich A, Neri G, Schwartz CE. A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24. <span><span class="ref-journal">Hum Mol Genet. </span>2003;<span class="ref-vol">12</span>:1959–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12913067" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12913067</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.deutsch.2011.566">Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schäfer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann J, Niesen FH, Sentürk A, Kunkel H, Brutschy B, Schleiff E, Knapp S, Acker-Palmer A, Grez M, McKeon F, Dötsch V. DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer. <span><span class="ref-journal">Cell. </span>2011;<span class="ref-vol">144</span>:566–76.</span> [<a href="/pmc/articles/PMC3087504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3087504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21335238" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21335238</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.dishop.2009.1935">Dishop MK, Bree AF, Hicks MJ. Pathologic changes of skin and hair in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. <span><span class="ref-journal">Am J Med Genet. </span>2009;<span class="ref-vol">149A</span>:1935–41.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19697429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19697429</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.elliott.2006.1419">Elliott AM, Evans JA. Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients. <span><span class="ref-journal">Am J Med Genet A. </span>2006;<span class="ref-vol">140</span>:1419–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16688749" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16688749</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.enriquez.2016.2372">Enriquez A, Krivanek M, Flöttmann R, Peters H, Wilson M. Recurrence of split hand/foot malformation, cleft lip/palate, and severe urogenital abnormalities due to germline mosaicism for TP63 mutation. <span><span class="ref-journal">Am J Med Genet A. </span>2016;<span class="ref-vol">170</span>:2372–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27351625" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27351625</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.farrington.2009.1907">Farrington F, Lausten L. Oral findings in ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome. <span><span class="ref-journal">Am J Med Genet. </span>2009;<span class="ref-vol">149A</span>:1907–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19681142" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19681142</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.ferstl.2018.1727">Ferstl P, Wohlfart S, Schneider H. Sweating ability of patients with P63-associated syndromes. <span><span class="ref-journal">Eur J Pediatr. </span>2018;<span class="ref-vol">177</span>:1727–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30088137" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30088137</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.julapalli.2009.1900">Julapalli MR, Scher RK, Sybert VP, Siegfried EC, Bree AF. Dermatologic findings of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:1900–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19681128" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19681128</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.khandelwal.2019.1101">Khandelwal KD, van den Boogaard MH, Mehrem SL, Gebel J, Fagerberg C, van Beusekom E, van Binsbergen E, Topaloglu O, Steehouwer M, Gilissen C, Ishorst N, van Rooij IALM, Roeleveld N, Christensen K, Schoenaers J, Bergé S, Murray JC, Hens G, Devriendt K, Ludwig KU, Mangold E, Hoischen A, Zhou H, Dötsch V, Carels CEL, van Bokhoven H. Deletions and loss-of-function variants in TP63 associated with orofacial clefting. <span><span class="ref-journal">Eur J Hum Genet. </span>2019;<span class="ref-vol">27</span>:1101–12.</span> [<a href="/pmc/articles/PMC6777535/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6777535</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30850703" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30850703</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.lane.2009.1926">Lane MM, Dalton WT 3rd, Sherman SA, Bree AF, Czyzewski DI. Psychosocial functioning and quality of life in children and families affected by AEC syndrome. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:1926–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19504609" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19504609</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.leoyklang.2006.e28">Leoyklang P, Siriwan P, Shotelersuk V. A mutation of the p63 gene in non-syndromic cleft lip. <span><span class="ref-journal">J Med Genet. </span>2006;<span class="ref-vol">43</span>:e28. </span> [<a href="/pmc/articles/PMC2564545/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2564545</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16740912" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16740912</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.mcgrath.2001.221">McGrath JA, Duijf PH, Doetsch V, Irvine AD, de Waal R, Vanmolkot KR, Wessagowit V, Kelly A, Atherton DJ, Griffiths WA, Orlow SJ, van Haeringen A, Ausems MG, Yang A, McKeon F, Bamshad MA, Brunner HG, Hamel BC, van Bokhoven H. Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of TP63. <span><span class="ref-journal">Hum Mol Genet. </span>2001;<span class="ref-vol">10</span>:221–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11159940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11159940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.monti.2013.894">Monti P, Russo D, Bocciardi R, Foggetti G, Menichini P, Divizia MT, Lerone M, Graziano C, Wischmeijer A, Viadiu H, Ravazzolo R, Inga A, Fronza G. EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences. <span><span class="ref-journal">Hum Mutat. </span>2013;<span class="ref-vol">34</span>:894–904.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23463580" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23463580</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.motil.2009.1922">Motil KJ, Fete TJ. Growth, nutritional, and gastrointestinal aspects of ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC) syndrome. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:1922–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19676058" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19676058</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.oquinn.1998.130">O'Quinn JR, Hennekam RC, Jorde LB, Bamshad M. Syndromic ectrodactyly with severe limb, ectodermal, urogenital, and palatal defects maps to chromosome 19. <span><span class="ref-journal">Am J Hum Genet. </span>1998;<span class="ref-vol">62</span>:130–5.</span> [<a href="/pmc/articles/PMC1376811/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1376811</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9443880" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9443880</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.pashayan.1974.105">Pashayan HM, Pruzansky S, Solomon L. The EEC syndrome. Report of six patients. <span><span class="ref-journal">Birth Defects Orig Artic Ser. </span>1974;<span class="ref-vol">10</span>:105–27.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/4425508" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4425508</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.restelli.2014.3830">Restelli M, Lopardo T, Lo Iacono N, Garaffo G, Conte D, Rustighi A, Napoli M, Del Sal G, Perez-Morga D, Costanzo A, Merlo GR, Guerrini L. DLX5, FGF8 and Pin1 isomerase control ΔNp63α protein stability during limb development: a regulatory loop at the basis of the SHFM and EEC congenital malformations. <span><span class="ref-journal">Hum Mol Genet. </span>2014;<span class="ref-vol">23</span>:3830–42.</span> [<a href="/pmc/articles/PMC4065156/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4065156</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24569166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24569166</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.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. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.rinne.2007.262">Rinne T, Brunner HG, van Bokhoven H. p63-associated disorders. <span><span class="ref-journal">Cell Cycle. </span>2007;<span class="ref-vol">6</span>:262–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17224651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17224651</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.rinne.2008.1968">Rinne T, Clements SE, Lamme E, Duijf PH, Bolat E, Meijer R, Scheffer H, Rosser E, Tan TY, McGrath JA, Schalkwijk J, Brunner HG, Zhou H, van Bokhoven H. A novel translation re-initiation mechanism for the p63 gene revealed by amino-terminal truncating mutations in Rapp-Hodgkin/Hay-Wells-like syndromes. <span><span class="ref-journal">Hum Mol Genet. </span>2008;<span class="ref-vol">17</span>:1968–77.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18364388" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18364388</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.rinne.2006a.1396">Rinne T, Hamel B, van Bokhoven H, Brunner HG. Pattern of p63 mutations and their phenotypes--update. <span><span class="ref-journal">Am J Med Genet A. </span>2006a;<span class="ref-vol">140</span>:1396–406.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16691622" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16691622</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.rinne.2006b.904">Rinne T, Spadoni E, Kjaer KW, Danesino C, Larizza D, Kock M, Huoponen K, Savontaus M-L, Aaltonen M, Duijf P, Brunner HG, Penttinen M, van Bokhoven H. Delineation of the ADULT syndrome phenotype due to arginine 298 mutgations of the p63 gene. <span><span class="ref-journal">Eur J Hum Genet. </span>2006b;<span class="ref-vol">14</span>:904–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16724007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16724007</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.rouleau.2011.1672">Rouleau M, Medawar A, Hamon L, Shivtiel S, Wolchinsky Z, Zhou H, De Rosa L, Candi E, de la Forest Divonne S, Mikkola ML, van Bokhoven H, Missero C, Melino G, Pucéat M, Aberdam D. TAp63 is important for cardiac differentiation of embryonic stem cells and heart development. <span><span class="ref-journal">Stem Cells. </span>2011;<span class="ref-vol">29</span>:1672–83.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21898690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21898690</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.sethi.2015.584">Sethi I, Romano R-A, Gluck C, Smalley K, Vojtesek B, Buck MJ, Sinha S. A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues. <span><span class="ref-journal">BMC Genomics. </span>2015;<span class="ref-vol">16</span>:584.</span> [<a href="/pmc/articles/PMC4528692/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4528692</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26251276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26251276</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.shalomfeuerstein.2013.2152">Shalom-Feuerstein R, Serror L, Aberdam E, Müller FJ, van Bokhoven H, Wiman KG, Zhou H, Aberdam D, Petit I. Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2013;<span class="ref-vol">110</span>:2152–6.</span> [<a href="/pmc/articles/PMC3568301/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3568301</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23355677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23355677</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.siegfried.2005.1591">Siegfried E, Bree A, Fete M, Sybert V. Skin erosions and wound healing in ankyloblepharon-ectodermal defect – cleft lip and/or palate. <span><span class="ref-journal">Arch Dermatol. </span>2005;<span class="ref-vol">141</span>:1591–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16365264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16365264</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.soares.2018.1179">Soares E, Zhou H. Master regulatory role of p63 in epidermal development and disease. <span><span class="ref-journal">Cell Mol Life Sci. </span>2018;<span class="ref-vol">75</span>:1179–90.</span> [<a href="/pmc/articles/PMC5843667/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5843667</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29103147" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29103147</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.spranger.1988.202">Spranger M, Schapera J. Anomalous inheritance in a kindred with split hand, split foot malformation. <span><span class="ref-journal">Eur J Pediatr. </span>1988;<span class="ref-vol">147</span>:202–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/3366140" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3366140</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.stenson.2017.665">Stenson PD, Mort M, Ball EV, Evans K, Hayden M, Heywood S, Hussain M, Phillips AD, Cooper DN. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. <span><span class="ref-journal">Hum Genet. </span>2017;<span class="ref-vol">136</span>:665–77.</span> [<a href="/pmc/articles/PMC5429360/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5429360</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28349240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28349240</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.sutton.2009.1916">Sutton VR, Plunkett K, Dang DX, Lewis RA, Bree AF, Bacino CA. Craniofacial and anthropometric phenotype in ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (Hay-Wells syndrome) in a cohort of 17 patients. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:1916–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19676059" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19676059</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.terrinoni.2013.7300">Terrinoni A, Serra V, Bruno E, Strasser A, Valente E, Flores ER, van Bokhoven H, Lu X, Knight RA, Melino G. Role of p63 and the Notch pathway in cochlea development and sensorineural deafness. <span><span class="ref-journal">Proc Natl Acad Sci USA. </span>2013;<span class="ref-vol">110</span>:7300–5.</span> [<a href="/pmc/articles/PMC3645580/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3645580</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23589895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23589895</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.ugur.2008.2644">Ugur SA, Tolun A. Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation. <span><span class="ref-journal">Hum Mol Genet. </span>2008;<span class="ref-vol">17</span>:2644–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18515319" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18515319</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.van_bokhoven.2001.481">van Bokhoven H, Hamel BC, Bamshad M, Sangiorgi E, Gurrieri F, Duijf PH, Vanmolkot KR, van Beusekom E, van Beersum SE, Celli J, Merkx GF, Tenconi R, Fryns JP, Verloes A, Newbury-Ecob RA, Raas-Rotschild A, Majewski F, Beemer FA, Janecke A, Chitayat D, Crisponi G, Kayserili H, Yates JR, Neri G, Brunner HG. p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. <span><span class="ref-journal">Am J Hum Genet. </span>2001;<span class="ref-vol">69</span>:481–92.</span> [<a href="/pmc/articles/PMC1235479/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1235479</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11462173" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11462173</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.van_bokhoven.1999.538">van Bokhoven H, Jung M, Smits AP, van Beersum S, Rüschendorf F, van Steensel M, Veenstra M, Tuerlings JH, Mariman EC, Brunner HG, Wienker TF, Reis A, Ropers HH, Hamel BC. Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27. <span><span class="ref-journal">Am J Hum Genet. </span>1999;<span class="ref-vol">64</span>:538–46.</span> [<a href="/pmc/articles/PMC1377763/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1377763</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9973291" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9973291</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.van_zelststams.2009.1558">van Zelst-Stams WA, van Steensel MA. A novel TP63 mutation in family with ADULT syndrome presenting with eczema and hypothelia. <span><span class="ref-journal">Am J Med Genet A. </span>2009;<span class="ref-vol">149A</span>:1558–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19530185" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19530185</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="aec.REF.zarnegar.2012.435">Zarnegar BJ, Webster DE, Lopez-Pajares V, Vander Stoep Hunt B, Qu K, Yan KJ, Berk DR, Sen GL, Khavari PA. Genomic profiling of a human organotypic model of AEC syndrome reveals ZNF750 as an essential downstream target of mutant TP63. <span><span class="ref-journal">Am J Hum Genet. </span>2012;<span class="ref-vol">91</span>:435–43.</span> [<a href="/pmc/articles/PMC3511987/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3511987</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22922031" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22922031</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK43797_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">V Reid Sutton</span>, MD<div class="affiliation small">Professor, Department of Molecular and Human Genetics
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Baylor College of Medicine;
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Texas Children's Hospital
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Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.snerdlihcsaxet@nottusrv" class="oemail">gro.snerdlihcsaxet@nottusrv</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Hans van Bokhoven</span>, PhD<div class="affiliation small">Professor, Molecular Neurogenetics
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Department of Human Genetics
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Radboud University Medical Center
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Nijmegen, the Netherlands<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ln.cmuduobdar@nevohkobnav.snah" class="oemail">ln.cmuduobdar@nevohkobnav.snah</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">June 8, 2010</span>; Last Update: <span itemprop="dateModified">April 1, 2021</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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use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
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Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
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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>Sutton VR, van Bokhoven H. TP63-Related Disorders. 2010 Jun 8 [Updated 2021 Apr 1]. 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/tnxb-eds/?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/trio-id/?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="figobaecTc"><div id="aec.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TP63</i>-Related Disorders: Included Phenotypes <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_aec.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome)</div><ul><li class="half_rhythm"><div>Rapp-Hodgkin syndrome</div></li></ul></li><li class="half_rhythm"><div>Acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome)</div></li><li class="half_rhythm"><div>Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3)</div></li><li class="half_rhythm"><div>Limb-mammary syndrome</div></li><li class="half_rhythm"><div>Split-hand/foot malformation type 4 (SHFM4)</div></li><li class="half_rhythm"><div>Isolated cleft lip/cleft palate (orofacial cleft 8)</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">For synonyms and outdated names see <a href="#aec.Nomenclature">Nomenclature</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="aec.TF.c.1"><p class="no_margin">For other genetic causes of these phenotypes, see <a href="#aec.Differential_Diagnosis">Differential Diagnosis</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobaecTmoleculargenetictestingusedin"><div id="aec.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>TP63</i>-Related Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.T.molecular_genetic_testing_used_in_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_aec.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_aec.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_aec.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TP63</i>
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</td><td headers="hd_h_aec.T.molecular_genetic_testing_used_in_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_aec.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">99% <sup>4</sup></td></tr><tr><td headers="hd_h_aec.T.molecular_genetic_testing_used_in_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_aec.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare <sup>4, 6</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="aec.TF.1.1"><p class="no_margin">See <a href="/books/NBK43797/?report=reader#aec.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="aec.TF.1.2"><p class="no_margin">See <a href="#aec.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="aec.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="aec.TF.1.4"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#aec.REF.stenson.2017.665" rid="aec.REF.stenson.2017.665">Stenson et al 2017</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="aec.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include 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 class="bkr_refwrap"><dt>6. </dt><dd><div id="aec.TF.1.6"><p class="no_margin">A single case report of a four-exon deletion of <i>TP63</i> has been reported in an individual with EEC3 [<a class="bibr" href="#aec.REF.aradhya.2012.594" rid="aec.REF.aradhya.2012.594">Aradhya et al 2012</a>]. Partial deletions of <i>TP63</i> have been reported in families with orofacial cleft (with or without other findings of a <i>TP63</i>-related disorder) [<a class="bibr" href="#aec.REF.khandelwal.2019.1101" rid="aec.REF.khandelwal.2019.1101">Khandelwal et al 2019</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobaecTtp63relateddisorderscomparisono"><div id="aec.T.tp63related_disorders_comparison_o" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>TP63</i>-Related Disorders: Comparison of Phenotypes by Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.tp63related_disorders_comparison_o/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.tp63related_disorders_comparison_o_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" rowspan="2" colspan="2" scope="colgroup" headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" colspan="6" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;"><i>TP63</i>-Related Disorder</th></tr><tr><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">AEC</th><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ADULT</th><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">EEC3</th><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Limb-<br />mammary</th><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SHFM4</th><th headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2" id="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orofacial<br />cleft 8</th></tr></thead><tbody><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ankyloblepharon filiforme adnatum</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Ectodermal dysplasia</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypohidrosis <sup>1</sup></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Nail dysplasia</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sparse hair</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Tooth abnormalities</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cleft lip/palate</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Split-hand/foot malformation / syndactyly</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Lacrimal duct obstruction</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dermal erosions</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypopigmentation</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypospadias</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Trismus</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Excessive freckling</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypoplastic breasts</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_1" colspan="2" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Hypoplastic nipples</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X</td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_aec.T.tp63related_disorders_comparison_o_1_1_1_2 hd_h_aec.T.tp63related_disorders_comparison_o_1_1_2_6" 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">ADULT = acro-dermato-ungual-lacrimal-tooth; AEC = ankyloblepharon-ectodermal defects-cleft lip/palate; EEC3 = ectrodactyly (split-hand/foot malformation), ectodermal dysplasia, cleft lip/palate syndrome 3; SHFM4 = split-hand/foot malformation type 4</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="aec.TF.2.1"><p class="no_margin">Mostly subjective</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobaecTgenesofinterestinthedifferent"><div id="aec.T.genes_of_interest_in_the_different" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of <i>TP63</i>-Related Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.genes_of_interest_in_the_different/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.genes_of_interest_in_the_different_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TP63</i>-Related Disorder</th><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Differential Diagnosis</th><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene/<br />Genetic<br />Mechanism</th><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Overlapping Features</th><th id="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Features</th></tr></thead><tbody><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>AEC syndrome</b>
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ebs/?report=reader">Epidermolysis bullosa simplex</a> (EBS)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EXPH5</i>
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<br />
|
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<i>KRT5</i>
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<br />
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<i>KRT14</i>
|
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<br />
|
|
<i>TGM5</i>
|
|
</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skin erosions at birth</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Erosions in AEC syndrome are typically more superficial & not assoc w/formation of bullae.</div></li><li class="half_rhythm"><div>Nondermatologic features & dermatopathology also distinguish EBS from AEC syndrome.</div></li></ul>
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</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/li-ar/?report=reader">Autosomal recessive congenital ichthyosis</a>
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ABCA12</i>
|
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<br />
|
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<i>ALOX12B</i>
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<br />
|
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<i>ALOXE3</i>
|
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<br />
|
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<i>CASP14</i>
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<br />
|
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<i>CERS3</i>
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<br />
|
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<i>CYP4F22</i>
|
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<br />
|
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<i>LIPN</i>
|
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<br />
|
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<i>NIPAL4</i>
|
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<br />
|
|
<i>PNPLA1</i>
|
|
<br />
|
|
<i>SDR9C7</i>
|
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<br />
|
|
<i>SLC27A4</i>
|
|
<br />
|
|
<i>TGM1</i>
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|
</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Erythroderma w/collodion membrane in newborn period <sup>1</sup></td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AEC is not assoc w/collodion membrane or ichthyosis.</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Curly hair-ankyloblepharon-nail dysplasia syndrome (CHANDS)<br />(OMIM <a href="https://omim.org/entry/214350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">214350</a>)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>RIPK4</i>
|
|
</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ankyloblepharon & hair changes</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CHANDS typically does not incl significant facial/oral clefting or skin erosions that are virtually universal in AEC syndrome.</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Cocoon syndrome <sup>2</sup></td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHUK</i>
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />AD</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ankyloblepharon, cleft lip/palate, ectodermal dysplasia</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cocoon syndrome is assoc w/hypogammaglobulinemia & recurrent infections (features not observed in AEC syndrome)</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>SHFM4</b>
|
|
</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SHFM1<br />(OMIM <a href="https://omim.org/entry/183600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">183600</a>)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DLX5</i>
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Split-hand/foot malformation</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>SHFM1 is assoc w/high incidence of hearing loss.</div></li><li class="half_rhythm"><div>Findings are largely restricted to limbs.</div></li><li class="half_rhythm"><div>Dental & lacrimal duct abnormalities are seen in <10% of persons. <sup>3</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">SHFM3<br />(OMIM <a href="https://omim.org/entry/246560" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">246560</a>)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10q24 contiguous gene duplication</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">SHFM3 is not assoc w/lacrimal, dental, or ectodermal abnormalities (beyond nail abnormalities assoc w/developmental defects of the digits). <sup>4</sup></td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">SHFM6<br />(OMIM <a href="https://omim.org/entry/225300" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">225300</a>)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>WNT10B</i> <sup>5</sup></td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">SHFM6 is not assoc w/lacrimal, dental, or ectodermal abnormalities.</td></tr><tr><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b><i>TP63</i>-related disorders generally</b>
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/x-hed/?report=reader">Hypohidrotic ectodermal dysplasia</a> (HED)</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>EDA</i>
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<br />
|
|
<i>EDAR</i>
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<br />
|
|
<i>EDARADD</i>
|
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<br />
|
|
<i>WNT10A</i>
|
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</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR<br />XL</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypotrichosis, hypohidrosis, hypodontia</td><td headers="hd_h_aec.T.genes_of_interest_in_the_different_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypohidrosis in HED is severe enough to impair body temperature regulation, a problem not seen in <i>TP63</i>-related disorders.</div></li><li class="half_rhythm"><div>Orofacial clefting, universal in AEC syndrome, is not typically seen in HED.</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">AEC = ankyloblepharon-ectodermal defects-cleft lip/palate; AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SHFM = split-hand/foot malformation; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="aec.TF.3.1"><p class="no_margin">
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<a class="bibr" href="#aec.REF.siegfried.2005.1591" rid="aec.REF.siegfried.2005.1591">Siegfried et al [2005]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="aec.TF.3.2"><p class="no_margin">
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<a class="bibr" href="#aec.REF.cadieuxdion.2018.41" rid="aec.REF.cadieuxdion.2018.41">Cadieux-Dion et al [2018]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="aec.TF.3.3"><p class="no_margin">
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<a class="bibr" href="#aec.REF.elliott.2006.1419" rid="aec.REF.elliott.2006.1419">Elliott & Evans [2006]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="aec.TF.3.4"><p class="no_margin"><a class="bibr" href="#aec.REF.de_mollerat.2003.1959" rid="aec.REF.de_mollerat.2003.1959">de Mollerat et al [2003]</a>, <a class="bibr" href="#aec.REF.elliott.2006.1419" rid="aec.REF.elliott.2006.1419">Elliott & Evans [2006]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="aec.TF.3.5"><p class="no_margin">Interestingly, all but one of the affected individuals in the initial pedigree also had promoter polymorphism in <i>TP63</i> [<a class="bibr" href="#aec.REF.ugur.2008.2644" rid="aec.REF.ugur.2008.2644">Ugur & Tolun 2008</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobaecTrecommendedevaluationsfollowing"><div id="aec.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with a <i>TP63</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_aec.T.recommended_evaluations_following_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_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ocular issues</b>
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</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for ankyloblepharon, lacrimal duct atresia/obstruction, dry eyes, & blepharitis.</td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin, hair, & nail</b>
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<br />
|
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<b>issues</b>
|
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</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dermatologic eval</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dental anomalies</b>
|
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</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dental & prosthodontics evals</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for need for implants.</td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft lip/palate</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eval by multispecialty cleft team</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Hearing loss</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Otolaryngologic eval & auditory evoked responses</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Breast/nipple</b>
|
|
<br />
|
|
<b>asymmetry</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Plastic surgery eval</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Growth delay</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nutritional eval</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Further assessment by gastroenterologist may be needed.</td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Developmental</b>
|
|
<br />
|
|
<b>delay</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Limb</b>
|
|
<br />
|
|
<b>malformations</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>OT/PT evals</div></li><li class="half_rhythm"><div>Hand surgery eval</div></li></ul>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Genetic</b>
|
|
<br />
|
|
<b>counseling</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_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_aec.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of a <i>TP63</i>-related disorder to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_aec.T.recommended_evaluations_following_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>
|
|
<br />
|
|
<b>resources</b>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess:
|
|
<ul><li class="half_rhythm"><div>Use of community or <a href="#aec.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>Need for social work involvement for parental support;</div></li><li class="half_rhythm"><div>Impact of phenotype on normal life & need for counseling.</div></li></ul>
|
|
</td><td headers="hd_h_aec.T.recommended_evaluations_following_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">MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="aec.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="figobaecTtreatmentofmanifestationsinind"><div id="aec.T.treatment_of_manifestations_in_ind" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with a <i>TP63</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.treatment_of_manifestations_in_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Ankyloblepharon filiforme adnatum</b>
|
|
</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">These strands of tissue between upper & lower eyelids are often small & autolyse shortly after birth; larger ones may require surgical separation by ophthalmologist.</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Lacrimal duct atresia/obstruction</b>
|
|
</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possible need for probing or surgical intervention per ophthalmologist</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Dry eyes / blepharitis</b>
|
|
</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hydrating ocular drops or gels</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Skin erosions</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gentle wound care & periodic, dilute bleach soaks (Dakins solution) to prevent secondary infection</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Occlusive dressings should not be used, as they tend to stimulate granulation tissue.</td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Treat secondary infections w/topical or oral antibiotics or antifungal agents when appropriate.</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Empiric treatment (i.e., use of antibiotic w/o culture-proven infection) is not recommended.</td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Infants w/severe skin erosions: monitor & treat aggressively for dehydration, electrolyte imbalances, malnutrition, & secondary infection & sepsis.</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sparse hair / alopecia</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wigs can be used as desired.</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hypodontia</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Childhood: consider dentures.</div></li><li class="half_rhythm"><div>Teen or early-adult: consider dental implants.</div></li></ul>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft lip/palate</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Care managed by a multispecialty cleft team</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing loss</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myringotomy for conductive hearing loss from chronic otitis media</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Breast/nipple asymmetry</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Females: significant breast asymmetry may be corrected w/plastic surgery.</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Growth delay</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Optimization of oral caloric intake</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrostomy tube placement may be considered.</td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental delay</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment & treatment by developmental pediatrician &/or child neuropsychologist</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Limb malformations</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OT & hand/foot surgery as needed to optimize function</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychological impact of phenotypic features</b>
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</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral for psychological support/counseling as necessary</td><td headers="hd_h_aec.T.treatment_of_manifestations_in_ind_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">OT = occupational therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobaecTrecommendedsurveillanceforindiv"><div id="aec.T.recommended_surveillance_for_indiv" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with a <i>TP63</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.T.recommended_surveillance_for_indiv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.T.recommended_surveillance_for_indiv_lrgtbl__"><table><thead><tr><th id="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_aec.T.recommended_surveillance_for_indiv_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_aec.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypodontia</td><td headers="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prosthodontic assessment</td><td headers="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per dental specialist</td></tr><tr><td headers="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing loss</td><td headers="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic testing</td><td headers="hd_h_aec.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per audiologist/otolaryngologist</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobaecmolgenTA"><div id="aec.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>TP63-Related Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK43797/table/aec.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_aec.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_aec.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_aec.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_aec.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_aec.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_aec.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_aec.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/8626" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>TP63</i>
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</a>
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</td><td headers="hd_b_aec.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=8626" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3q28</a>
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</td><td headers="hd_b_aec.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/Q9H3D4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Tumor protein 63</a>
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</td><td headers="hd_b_aec.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://databases.lovd.nl/shared/genes/TP63" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TP63 @ LOVD</a>
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</td><td headers="hd_b_aec.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=TP63" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TP63</a>
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</td><td headers="hd_b_aec.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TP63[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TP63</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="aec.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>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<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="figobaecmolgenTB"><div id="aec.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for TP63-Related Disorders (<a href="/omim/103285,106260,129400,603273,603543,604292,605289,618149" 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/NBK43797/table/aec.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__aec.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/103285" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">103285</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ADULT SYNDROME</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/106260" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">106260</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ANKYLOBLEPHARON-ECTODERMAL DEFECTS-CLEFT LIP/PALATE; AEC</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/129400" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">129400</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RAPP-HODGKIN SYNDROME; RHS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603273" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603273</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TUMOR PROTEIN p63; TP63</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603543" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603543</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LIMB-MAMMARY SYNDROME; LMS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604292" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604292</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ECTRODACTYLY, ECTODERMAL DYSPLASIA, AND CLEFT LIP/PALATE SYNDROME 3; EEC3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/605289" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605289</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPLIT-HAND/FOOT MALFORMATION 4; SHFM4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/618149" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">618149</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OROFACIAL CLEFT 8; OFC8</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobaecF1"><div id="aec.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK43797/bin/aec-Image001.jpg" alt="Figure 1. . Typical and common TP63 pathogenic variants identified in various disorders as indicated by color key." /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Typical and common <i>TP63</i> pathogenic variants identified in various disorders as indicated by color key. Pathogenic variants indicated by * are specific for the ΔNp63α isoform and their numbering is based on the respective reference sequences (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001114982.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001114982.1</a>, <a href="https://www.ncbi.nlm.nih.gov/protein/NP_001108454.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001108454.1</a>). The numbering of other pathogenic variants is based on the reference sequences for TAp63α (<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_003722.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_003722.5</a>, <a href="https://www.ncbi.nlm.nih.gov/protein/NP_003713.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_003713.3</a>). Note that the variant indicated by # (R97C) is specific for TAp63α.</p><p>EEC = ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome</p><p>LMS = limb-mammary syndrome</p><p>ADULT = acro-dermo-ungual-lacrimal-tooth syndrome</p><p>AEC = ankyloblepharon-ectodermal defects-cleft lip/palate syndrome</p><p>SHFM4 = split-hand/foot malformation type 4</p><p>NSCL = nonsyndromic cleft lip</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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