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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Hyaline Fibromatosis Syndrome - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="Hyaline Fibromatosis Syndrome">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2023/05/11">
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<meta name="citation_author" content="Joseph TC Shieh">
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<meta name="citation_author" content="H Eugene Hoyme">
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<meta name="citation_author" content="Laura T Arbour">
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<meta name="citation_keywords" content="Inherited Systemic Hyalinosis">
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<meta name="citation_keywords" content="ANTXR2-Related Hyaline Fibromatosis Syndrome">
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<meta name="citation_keywords" content="Inherited Systemic Hyalinosis">
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<meta name="citation_keywords" content="ANTXR2-Related Hyaline Fibromatosis Syndrome">
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<meta name="citation_keywords" content="Anthrax toxin receptor 2">
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<meta name="citation_keywords" content="ANTXR2">
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<meta name="citation_keywords" content="Hyaline Fibromatosis Syndrome">
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<meta name="DC.Title" content="Hyaline Fibromatosis Syndrome">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Joseph TC Shieh">
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<meta name="DC.Contributor" content="H Eugene Hoyme">
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<meta name="DC.Contributor" content="Laura T Arbour">
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<meta name="DC.Date" content="2023/05/11">
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<meta name="description" content="Hyaline fibromatosis syndrome (HFS) is characterized by hyaline deposits in the papillary dermis and other tissues. It can present at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood.">
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<meta name="og:title" content="Hyaline Fibromatosis Syndrome">
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<meta name="og:description" content="Hyaline fibromatosis syndrome (HFS) is characterized by hyaline deposits in the papillary dermis and other tissues. It can present at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood.">
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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="_NBK1525_"><span class="title" itemprop="name">Hyaline Fibromatosis Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Inherited Systemic Hyalinosis, <i>ANTXR2</i>-Related Hyaline Fibromatosis Syndrome</div><p class="contribs">Shieh JTC, Hoyme HE, Arbour LT.</p><p class="fm-aai"><a href="#_NBK1525_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 18 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="sys-h.Summary" itemprop="description"><h2 id="_sys-h_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Hyaline fibromatosis syndrome (HFS) is characterized by hyaline deposits in the papillary dermis and other tissues. It can present at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of HFS is established in a proband with characteristic clinical features and/or biallelic pathogenic (or likely pathogenic) variants in <i>ANTXR2</i> identified by molecular genetic testing. Skin biopsy may reveal hyaline material accumulation in the dermis or nondiagnostic findings; intestinal biopsy may demonstrate villous atrophy and lymphangiectasia. Skeletal x-rays may reveal osteopenia, periosteal reaction, and lucent lesions.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Possible nasogastric tube, gastrostomy tube feeding, or parenteral nutrition under supervision of a gastroenterologist and nutritionist; nutrition tailored for the possibility of malabsorption or lymphangiectasia; hydration and albumin infusions for protein-losing enteropathy; physiotherapy for joint contractures can be considered although pain may be problematic; nonsteroidal anti-inflammatory drugs, opiates, and possibly gabapentin for pain; gentle handling; splinting may reduce pain; consultation with a pain management specialist as needed; lesions that obstruct the airway or interfere with feedings can be excised, but may recur; anesthesiologists need to be aware of potential difficulties with endotracheal intubation; perianal masses may be resected; treatment of skin nodules as recommended by dermatology and/or plastic surgery; infections are treated based on the site of infection and causative agent; consider family counseling to manage chronic medical condition.</p><p><i>Surveillance:</i> The following as needed based on clinical presentation: antibody levels and serum albumin; evaluation for gastrointestinal malabsorption; nutrition assessment; history and examination for contracture progression and pain; examination for concerning lesions; examination for oral lesions that affect feeding/nutrition and dental complications; cardiac assessment.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>HFS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an <i>ANTXR2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being unaffected and a carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible once the <i>ANTXR2</i> pathogenic variants have been identified in an affected family member.</p></div></div><div id="sys-h.Diagnosis"><h2 id="_sys-h_Diagnosis_">Diagnosis</h2><div id="sys-h.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Hyaline fibromatosis syndrome (HFS) <b>should be suspected</b> in probands with the following clinical, laboratory, histopathology, and radiographic features. Clinical features are presented in order of their specificity for clinical diagnosis.</p><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div><b>Hyperpigmented skin over bony prominences.</b> Purplish patches develop over the medial and lateral malleoli of the ankles, metacarpophalangeal joints, spine, and elbows.</div></li><li class="half_rhythm"><div><b>Progressive contractures</b> (e.g., hip, knee and elbow flexion, ankle dorsiflexion, wrist extension with flexion of proximal interphalangeal and distal interphalangeal joints) that may be congenital and/or cause decreased intrauterine movement. Some individuals have only mild contractures.</div></li><li class="half_rhythm"><div><b>Possible pain or excessive crying</b> with passive movement</div></li><li class="half_rhythm"><div><b>Failure to thrive.</b> Postnatal-onset growth deficiency is common. Some children develop chronic diarrhea and protein-losing enteropathy.</div></li><li class="half_rhythm"><div>
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<b>Gingival thickening</b>
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</div></li><li class="half_rhythm"><div><b>Skin nodules</b> (e.g., pearly papules on the head and neck; skin nodules, papules, and fleshy lesions periorally and perianally)</div></li><li class="half_rhythm"><div><b>Characteristic facies.</b> A depressed nasal bridge, variable ear malformations (large, simple or low-set ears, and preauricular skin tags), and a slightly coarse facial appearance may be present.</div></li><li class="half_rhythm"><div><b>Normal ophthalmologic examination</b> can be used to differentiate HFS from some lysosomal storage disorders.</div></li></ul><p>
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<b>Laboratory features</b>
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</p><ul><li class="half_rhythm"><div>Serum albumin may be low.</div></li><li class="half_rhythm"><div>Normal or slightly elevated ESR, anemia, and/or thrombocytosis</div></li><li class="half_rhythm"><div>Immunoglobulin levels may be low and cellular immune responses depressed.</div></li><li class="half_rhythm"><div>CD3 and CD4 lymphocyte subsets and ANA are unremarkable.</div></li></ul><p>
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<b>Histopathology</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Skin biopsy.</b> Light microscopy demonstrates hyaline material in the dermis.</div><div class="half_rhythm">Note: This finding may not be evident in the early stages of the disease [<a class="bibr" href="#sys-h.REF.arbour.2001" rid="sys-h.REF.arbour.2001">Arbour et al 2001</a>]. The hyaline material appears as an amorphous eosinophilic substance that is periodic acid-Schiff (PAS) positive. It is thought to contain glycoproteins and collagen. The spindle-shaped fibroblasts dispersed in abundant amounts of hyaline material render a "chondroid appearance."</div><div class="half_rhythm">Electron microscopy demonstrates cells filled with fine, fibrillary material with an enlarged endoplasmic reticulum and Golgi apparatus.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Intestinal biopsy.</b> Villous atrophy, edema, lymphangiectasia, and hyalinosis may be seen in individuals with prominent gastrointestinal symptoms.</div></li></ul><p>
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<b>Radiographic features</b>
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</p><ul><li class="half_rhythm"><div>Skeletal radiographs. Generalized osteopenia, periosteal reaction, and lucent lesions are nonspecific findings that may affect long bones as well as the axial skeleton.</div></li><li class="half_rhythm"><div>Upper-gastrointestinal imaging studies may show rapid transit time.</div></li><li class="half_rhythm"><div>Brain MRI is unremarkable.</div></li></ul></div><div id="sys-h.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of HFS <b>is established</b> in a proband with the above <a href="#sys-h.Suggestive_Findings">suggestive findings</a> and/or biallelic pathogenic (or likely pathogenic) variants in <i>ANTXR2</i> identified by molecular genetic testing (see <a href="/books/NBK1525/table/sys-h.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobsyshTmoleculargenetictestingusedi">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#sys-h.REF.richards.2015.405" rid="sys-h.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>ANTXR2</i> variants of uncertain significance (or of one known <i>ANTXR2</i> pathogenic variant and one <i>ANTXR2</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, 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="#sys-h.Suggestive_Findings">Suggestive Findings</a> may be diagnosed using gene-targeted testing (see <a href="#sys-h.Option_1">Option 1</a>), whereas those in whom the diagnosis of HFS has not been considered are more likely to be diagnosed using genomic testing (see <a href="#sys-h.Option_2">Option 2</a>).</p><div id="sys-h.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>ANTXR2</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 only one or 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>ANTXR2</i> and other genes of interest (see <a href="#sys-h.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</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="sys-h.Option_2"><h4>Option 2</h4><p>When the diagnosis of HFS is not immediately recognized, <b>comprehensive genomic testing</b> (which does not require the clinician to determine which gene is likely involved) is the most likely option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>If exome sequencing is not diagnostic, <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.</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="figsyshTmoleculargenetictestingusedi"><a href="/books/NBK1525/table/sys-h.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobsyshTmoleculargenetictestingusedi"><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="sys-h.T.molecular_genetic_testing_used_i"><a href="/books/NBK1525/table/sys-h.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobsyshTmoleculargenetictestingusedi">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Hyaline Fibromatosis Syndrome </p></div></div></div></div></div><div id="sys-h.Clinical_Characteristics"><h2 id="_sys-h_Clinical_Characteristics_">Clinical Characteristics</h2><div id="sys-h.Clinical_Description"><h3>Clinical Description</h3><p>Hyaline fibromatosis syndrome (HFS), named for the characteristic hyaline deposits in the papillary dermis and other tissues including the gastrointestinal tract of affected individuals, exhibits a broad spectrum of clinical severity [<a class="bibr" href="#sys-h.REF.casasalba.2018.1752" rid="sys-h.REF.casasalba.2018.1752">Casas-Alba et al 2018</a>, <a class="bibr" href="#sys-h.REF.cozma.2019.209" rid="sys-h.REF.cozma.2019.209">Cozma et al 2019</a>]. Individuals may present at birth or in infancy with severe pain with movement, progressive joint contractures, skin that is firm to palpation, and characteristic hyperpigmented macules/patches over bony prominences of the joints, especially the ankles, wrists, and metacarpal-phalangeal joints [<a class="bibr" href="#sys-h.REF.shieh.2006.e1485" rid="sys-h.REF.shieh.2006.e1485">Shieh et al 2006</a>, <a class="bibr" href="#sys-h.REF.elkamah.2009.6" rid="sys-h.REF.elkamah.2009.6">El-Kamah & Mostafa 2009</a>, <a class="bibr" href="#sys-h.REF.hammoudah.2016.124" rid="sys-h.REF.hammoudah.2016.124">Hammoudah & El-Attar 2016</a>, <a class="bibr" href="#sys-h.REF.schussler.2018.17" rid="sys-h.REF.schussler.2018.17">Schussler et al 2018</a>]. Severely affected children can die in the first years of life, possibly from gastrointestinal involvement. Some individuals demonstrate a milder phenotype, which may be of later onset. Adults with significant symptoms have also been reported.</p><p>To date, at least 93 individuals have been identified with a pathogenic variant in <i>ANTXR2</i> [<a class="bibr" href="#sys-h.REF.cozma.2019.209" rid="sys-h.REF.cozma.2019.209">Cozma et al 2019</a>, <a class="bibr" href="#sys-h.REF.h_rter.2020.e1203" rid="sys-h.REF.h_rter.2020.e1203">Härter et al 2020</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshTfeaturesofhyalinefibromatosis"><a href="/books/NBK1525/table/sys-h.T.features_of_hyaline_fibromatosis/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobsyshTfeaturesofhyalinefibromatosis"><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="sys-h.T.features_of_hyaline_fibromatosis"><a href="/books/NBK1525/table/sys-h.T.features_of_hyaline_fibromatosis/?report=objectonly" target="object" rid-ob="figobsyshTfeaturesofhyalinefibromatosis">Table 2. </a></h4><p class="float-caption no_bottom_margin">Features of Hyaline Fibromatosis Syndrome </p></div></div><p><b>Skin nodules and other manifestations.</b> Skin nodules and white-to-pink pearly papules that are a few millimeters in size are common on the face and neck. Fleshy lesions may appear in the perianal region. These lesions appear to develop and become more numerous over time. The skin is firm to palpation and has been described as thickened. Excessive diaphoresis is common.</p><p><b>Hyperpigmented skin over bony prominences.</b> Characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, spine, and elbows. The degree of hyperpigmentation varies depending on the baseline pigmentation of the skin [<a class="bibr" href="#sys-h.REF.arbour.2001" rid="sys-h.REF.arbour.2001">Arbour et al 2001</a>].</p><p><b>Progressive contractures.</b> Affected individuals can present with congenital contractures. Some mothers report deficient fetal activity during the pregnancy of the affected infant, and many parents note decreased passive and/or active movement of the extremities of their child. Contractures are progressive, and extremities become fixed with the hips and knees flexed and the ankles dorsiflexed. The elbows exhibit flexion contractures, and the wrists are typically positioned in extension with flexion contractures of the proximal interphalangeal and distal interphalangeal joints. Some individuals demonstrate milder features [<a class="bibr" href="#sys-h.REF.shieh.2006.e1485" rid="sys-h.REF.shieh.2006.e1485">Shieh et al 2006</a>].</p><p><b>Pain or excessive crying.</b> Severe pain with passive movement in infancy or early childhood is characteristic. Pathogenesis is unclear.</p><p><b>Failure to thrive.</b> Postnatal-onset growth deficiency is common. Villous atrophy, edema, and lymphangiectasia of the intestine can lead to malabsorption. Some children develop severe intractable protein-losing diarrhea, likely due to hyalinosis of the intestine. The clinical progression of severe cases has been delayed with regular gastrointestinal evaluation and nutritional support [Shieh, unpublished].</p><p><b>Gingival manifestations.</b> The gingivae are thickened. Affected individuals develop masses in the gingiva, which enlarge over time. Lesions that obstruct the airway or interfere with oral intake are particularly problematic. Lesions may recur after surgical excision.</p><p><b>Dental abnormalities</b> include malpositioned teeth, curved dental roots, or other dental abnormalities.</p><p><b>Characteristic facies.</b> A depressed nasal bridge, variable ear malformations (large, simple, or low-set ears; preauricular skin tags), and a slightly coarse facial appearance may be present.</p><p>
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<b>Other</b>
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</p><ul><li class="half_rhythm"><div>Cognitive function is preserved; however, individuals with delayed development have been reported [<a class="bibr" href="#sys-h.REF.nischal.2004.125" rid="sys-h.REF.nischal.2004.125">Nischal et al 2004</a>].</div></li><li class="half_rhythm"><div>Hepatomegaly may be present.</div></li><li class="half_rhythm"><div>Susceptibility to fractures may be increased.</div></li><li class="half_rhythm"><div>Recurrent infections may develop due to impaired cellular immune responses and reduced immunoglobulin levels [<a class="bibr" href="#sys-h.REF.klebanova.2009.127" rid="sys-h.REF.klebanova.2009.127">Klebanova & Schwindt 2009</a>].</div></li><li class="half_rhythm"><div>At least two clinically diagnosed individuals developed squamous cell carcinoma [<a class="bibr" href="#sys-h.REF.kawasaki.2001.200" rid="sys-h.REF.kawasaki.2001.200">Kawasaki et al 2001</a>, <a class="bibr" href="#sys-h.REF.shimizu.2005.650" rid="sys-h.REF.shimizu.2005.650">Shimizu et al 2005</a>] and an adult has been reported with colon cancer. The <i>ANTXR2</i> mutation status in these individuals is unknown.</div></li><li class="half_rhythm"><div>Cardiovascular involvement is largely unknown. One instance of atrial thrombus has been reported.</div></li></ul><p>
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<b>Prognosis</b>
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</p><ul><li class="half_rhythm"><div>Individuals with severe disease can succumb to infection or complications of protein-losing enteropathy.</div></li><li class="half_rhythm"><div>Some individuals demonstrate a milder phenotype, which may be of later onset with potential survival into adulthood.</div></li><li class="half_rhythm"><div>A clinical grading system for HFS has been proposed [<a class="bibr" href="#sys-h.REF.denadai.2012.732" rid="sys-h.REF.denadai.2012.732">Denadai et al 2012</a>] with grades from mild to severe/lethal. All grades have skin and/or gingival involvement, while increasing grades have joint and/or bone and internal organ involvement. Sepsis or organ failure is associated with the most severe forms.</div></li></ul><p><b>Milder phenotype.</b> Although joint contractures, skin hyperpigmentation, and skin lesions occur with the milder phenotype, the presentation is variable and disability may be less pronounced. Pain is less severe and may decrease with age. Short stature, limb shortening, and brachydactyly may be present. Intractable diarrhea is rare in milder forms of the disorder.</p><p><b>Pathology.</b> Myopathic changes on muscle biopsy may be evident [<a class="bibr" href="#sys-h.REF.zolkipli.2003.401" rid="sys-h.REF.zolkipli.2003.401">Zolkipli et al 2003</a>]. Only a few postmortem examinations have been reported. Hyaline deposition has been documented in the dermis, the small and large intestine, skeletal muscle, lymph nodes, thymus, spleen, thyroid, adrenals, and myocardium. Interstitial parenchymal fibrosis of the pancreas, skeletal muscle, lung, and liver was observed [<a class="bibr" href="#sys-h.REF.criado.2004.282" rid="sys-h.REF.criado.2004.282">Criado et al 2004</a>].</p></div><div id="sys-h.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p><a class="bibr" href="#sys-h.REF.hanks.2003.791" rid="sys-h.REF.hanks.2003.791">Hanks et al [2003]</a> reported on genotype/phenotype correlations in 17 families:</p><ul><li class="half_rhythm"><div>Those with at least one insertion/deletion in <i>ANTXR2</i> resulting in a translational frameshift had a severe phenotype (infantile systemic hyalinosis).</div></li><li class="half_rhythm"><div>In-frame and missense variants in the cytoplasmic domain were associated with a milder phenotype, with survival to adulthood without recurrent infections, diarrhea, or multiorgan failure. Skeletal manifestations, however, were variably present.</div></li></ul><p>A review of <i>ANTXR2</i> variant type and disease grade was published by <a class="bibr" href="#sys-h.REF.casasalba.2018.1752" rid="sys-h.REF.casasalba.2018.1752">Casas-Alba et al [2018]</a>; missense variants in the cytoplasmic domain were found to be less severe.</p></div><div id="sys-h.Nomenclature"><h3>Nomenclature</h3><p>Before the molecular basis of HFS was understood, severe and milder forms of the disorder were described as separate conditions (infantile systemic hyalinosis and juvenile hyaline fibromatosis, respectively). It is now known that both severe and mild forms of HFS are caused by pathogenic variants in <i>ANTXR2</i>.</p><p>In the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bibr" href="#sys-h.REF.unger.2023.1164" rid="sys-h.REF.unger.2023.1164">Unger et al 2023</a>], HFS is referred to as <i>ANTXR2-</i>related hyaline fibromatosis syndrome and is included in the genetic inflammatory or rheumatoid-like osteoarthropathies group.</p></div><div id="sys-h.Prevalence"><h3>Prevalence</h3><p>HFS is rare, but it has been recognized in families of various ethnic backgrounds on multiple continents.</p></div></div><div id="sys-h.Genetically_Related_Allelic_Disord"><h2 id="_sys-h_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>ANTXR2</i>.</p></div><div id="sys-h.Differential_Diagnosis"><h2 id="_sys-h_Differential_Diagnosis_">Differential Diagnosis</h2><p>The conditions summarized in <a href="/books/NBK1525/table/sys-h.T.other_genes_and_conditions_of_in/?report=objectonly" target="object" rid-ob="figobsyshTothergenesandconditionsofin">Table 3</a> exhibit some features similar to hyaline fibromatosis syndrome (HFS); however, HFS can be distinguished by the characteristic associated pain, hyperpigmented skin lesions, and perianal and perioral masses.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshTothergenesandconditionsofin"><a href="/books/NBK1525/table/sys-h.T.other_genes_and_conditions_of_in/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobsyshTothergenesandconditionsofin"><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="sys-h.T.other_genes_and_conditions_of_in"><a href="/books/NBK1525/table/sys-h.T.other_genes_and_conditions_of_in/?report=objectonly" target="object" rid-ob="figobsyshTothergenesandconditionsofin">Table 3. </a></h4><p class="float-caption no_bottom_margin">Other Genes and Conditions of Interest in the Differential Diagnosis of Hyaline Fibromatosis Syndrome </p></div></div><p><b>Note:</b> Periosteal reaction or fractures on skeletal radiographs in systemic hyalinosis have been mistaken for <b>non-accidental trauma</b>. The hyperpigmented skin lesions may mistakenly be considered post-traumatic, and the perianal masses can resemble condylomata, prompting a workup for an infectious etiology.</p></div><div id="sys-h.Management"><h2 id="_sys-h_Management_">Management</h2><div id="sys-h.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with hyaline fibromatosis syndrome (HFS), the evaluations summarized in <a href="/books/NBK1525/table/sys-h.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobsyshTrecommendedevaluationsfollowin">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) should be considered.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshTrecommendedevaluationsfollowin"><a href="/books/NBK1525/table/sys-h.T.recommended_evaluations_followin/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobsyshTrecommendedevaluationsfollowin"><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="sys-h.T.recommended_evaluations_followin"><a href="/books/NBK1525/table/sys-h.T.recommended_evaluations_followin/?report=objectonly" target="object" rid-ob="figobsyshTrecommendedevaluationsfollowin">Table 4. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Hyaline Fibromatosis Syndrome </p></div></div></div><div id="sys-h.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshTtreatmentofmanifestationsini"><a href="/books/NBK1525/table/sys-h.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobsyshTtreatmentofmanifestationsini"><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="sys-h.T.treatment_of_manifestations_in_i"><a href="/books/NBK1525/table/sys-h.T.treatment_of_manifestations_in_i/?report=objectonly" target="object" rid-ob="figobsyshTtreatmentofmanifestationsini">Table 5. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Hyaline Fibromatosis Syndrome </p></div></div></div><div id="sys-h.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshTrecommendedsurveillanceforind"><a href="/books/NBK1525/table/sys-h.T.recommended_surveillance_for_ind/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobsyshTrecommendedsurveillanceforind"><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="sys-h.T.recommended_surveillance_for_ind"><a href="/books/NBK1525/table/sys-h.T.recommended_surveillance_for_ind/?report=objectonly" target="object" rid-ob="figobsyshTrecommendedsurveillanceforind">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Hyaline Fibromatosis Syndrome </p></div></div></div><div id="sys-h.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#sys-h.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="sys-h.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="sys-h.Genetic_Counseling"><h2 id="_sys-h_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="sys-h.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Hyaline fibromatosis syndrome (HFS) is inherited in an autosomal recessive manner.</p></div><div id="sys-h.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., presumed to be carriers of one <i>ANTXR2</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an <i>ANTXR2</i> pathogenic variant and to allow reliable recurrence risk assessment. (<i>De novo</i> variants are known to occur at a low but appreciable rate in autosomal recessive disorders [<a class="bibr" href="#sys-h.REF.j_nsson.2017.519" rid="sys-h.REF.j_nsson.2017.519">Jónsson et al 2017</a>].)</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing HFS.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an <i>ANTXR2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being unaffected and a carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing HFS.</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with HFS are obligate heterozygotes (carriers) for a pathogenic variant.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>ANTXR2</i> pathogenic variant.</p></div><div id="sys-h.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>ANTXR2</i> pathogenic variants in the family.</p></div><div id="sys-h.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#sys-h.REF.huang.2022.389" rid="sys-h.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="sys-h.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p><b>Molecular genetic testing.</b> Once the <i>ANTXR2</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p><b>Ultrasound examination/imaging.</b> The utility of prenatal ultrasound examination is unclear; however, in a pregnancy at increased risk, detection of decreased fetal activity and contractures could suggest recurrence. (Note: One or both of these findings should also prompt consideration of HFS in a pregnancy not previously known to be at increased risk for the disorder.)</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="sys-h.Resources"><h2 id="_sys-h_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>American Chronic Pain Association</b>
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</div><div>
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<a href="https://www.acpanow.com/#/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.acpanow.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>MISS Foundation</b>
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</div><div>
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<i>International organization which provides immediate and ongoing support to grieving families after the death of a baby or young child from any cause</i>
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</div><div>PO Box 5333</div><div>Peoria AZ 85385-5333</div><div><b>Phone:</b> 888-455-6477 (toll-free); 623-979-1000</div><div><b>Fax:</b> 623-979-1001</div><div><b>Email:</b> info@missfoundation.org</div><div>
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<a href="http://www.missfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.missfoundation.org</a>
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</div></li></ul>
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</div><div id="sys-h.Molecular_Genetics"><h2 id="_sys-h_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="figsyshmolgenTA"><a href="/books/NBK1525/table/sys-h.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobsyshmolgenTA"><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="sys-h.molgen.TA"><a href="/books/NBK1525/table/sys-h.molgen.TA/?report=objectonly" target="object" rid-ob="figobsyshmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Hyaline Fibromatosis Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figsyshmolgenTB"><a href="/books/NBK1525/table/sys-h.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobsyshmolgenTB"><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="sys-h.molgen.TB"><a href="/books/NBK1525/table/sys-h.molgen.TB/?report=objectonly" target="object" rid-ob="figobsyshmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Hyaline Fibromatosis Syndrome (View All in OMIM) </p></div></div><div id="sys-h.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ANTXR2</i> encodes a transmembrane protein that is expressed in numerous organs in the body. ANTXR2 acts as a receptor and binds to subtrates such as collagen VI, which may lead to phosphorylation or ubiquitination. It also binds to laminin. ANTXR2 may activate matrix metalloproteinases such as MT1-MMP. ANTXR2 reduces proliferation of endothelial cells in culture. Knockout of <i>Antxr2</i> in mice led to uterine fibrosis [<a class="bibr" href="#sys-h.REF.reeves.2012.e34862" rid="sys-h.REF.reeves.2012.e34862">Reeves et al 2012</a>, <a class="bibr" href="#sys-h.REF.b_rgi.2017.15861" rid="sys-h.REF.b_rgi.2017.15861">Bürgi et al 2017</a>]. The cytoplasmic domain of ANTXR2 is also important in its function. Hyalinosis of the gastrointestinal tract may lead to protein-losing enteropathy [<a class="bibr" href="#sys-h.REF.shieh.2006.e1485" rid="sys-h.REF.shieh.2006.e1485">Shieh et al 2006</a>, <a class="bibr" href="#sys-h.REF.alreheili.2012.206" rid="sys-h.REF.alreheili.2012.206">Alreheili et al 2012</a>].</p><p><i>ANTXR2</i> is also known as <i>CMG2</i>, or capillary morphogenesis gene 2.</p><p><b>Mechanism of disease causation.</b> Loss of function</p></div></div><div id="sys-h.Chapter_Notes"><h2 id="_sys-h_Chapter_Notes_">Chapter Notes</h2><div id="sys-h.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>11 May 2023 (sw) Revision: "<i>ANTXR2</i>-Related Hyaline Fibromatosis Syndrome" added as a synonym; Nosology of Genetic Skeletal Disorders: 2023 Revision [<a class="bibr" href="#sys-h.REF.unger.2023.1164" rid="sys-h.REF.unger.2023.1164">Unger et al 2023</a>] added to <a href="#sys-h.Nomenclature">Nomenclature</a></div></li><li class="half_rhythm"><div>23 July 2020 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>11 April 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 February 2008 (me) Review posted live</div></li><li class="half_rhythm"><div>5 May 2004 (la) Original submission</div></li></ul></div></div><div id="sys-h.References"><h2 id="_sys-h_References_">References</h2><div id="sys-h.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.alreheili.2012.206">Alreheili K, AlMehaidib A, Alsaleem K, Banemi M, Aldekhail W, Al-Mayouf SM. Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy. <span><span class="ref-journal">Ann Saudi Med. </span>2012;<span class="ref-vol">32</span>:206–8.</span> [<a href="/pmc/articles/PMC6086646/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6086646</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22366835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22366835</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.arbour.2001">Arbour L, Reilly C, McGillivray B, Prendiville J, Dimmick J. Infantile systemic hyalinosis: A rare syndrome of progressive, painful contractures with peculiar hyperpigmentation and death in infancy. Greenwood, SC: Proceedings of the Greenwood Genetic Center; 2001.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.b_rgi.2017.15861">Bürgi J, Kunz B, Abrami L, Deuquet J, Piersigilli A, Scholl-Bürgi S, Lausch E, Unger S, Superti-Furga A, Bonaldo P, van der Goot FG. CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome. <span><span class="ref-journal">Nat Commun. </span>2017;<span class="ref-vol">8</span>:15861.</span> [<a href="/pmc/articles/PMC5472780/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5472780</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28604699" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28604699</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.casasalba.2018.1752">Casas-Alba D, Martínez-Monseny A, Pino-Ramírez RM, Alsina L, Castejón E, Navarro-Vilarrubí S, Pérez-Dueñas B, Serrano M, Palau F, García-Alix A. Hyaline fibromatosis syndrome: Clinical update and phenotype-genotype correlations. <span><span class="ref-journal">Hum Mutat. </span>2018;<span class="ref-vol">39</span>:1752–63.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30176098" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30176098</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.cozma.2019.209">Cozma C, Hovakimyan M, Iurașcu MI, Makhseed N, Selim LA, Alhashem AM, Ben-Omran T, Mahmoud IG, Al Menabawy NM, Al-Mureikhi M, Martin M, Demuth L, Yüksel Z, Beetz C, Bauer P, Rolfs A. Genetic, clinical and biochemical characterization of a large cohort of patients with hyaline fibromatosis syndrome. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2019;<span class="ref-vol">14</span>:209.</span> [<a href="/pmc/articles/PMC6712857/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6712857</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31455396" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31455396</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.criado.2004.282">Criado GR, González-Meneses A, Cañadas M, Rafel E, Yanes F, De Terreros IG. Infantile systemic hyalinosis: a clinicopathological study. <span><span class="ref-journal">Am J Med Genet A. </span>2004;<span class="ref-vol">129A</span>:282–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15326628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15326628</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.denadai.2012.732">Denadai R, Raposo-Amaral CE, Bertola D, Kim C, Alonso N, Hart T, Han S, Stelini RF, Buzzo CL, Raposo-Amaral CA, Hart PS. Identification of 2 novel ANTXR2 mutations in patients with hyaline fibromatosis syndrome and proposal of a modified grading system. <span><span class="ref-journal">Am J Med Genet A. </span>2012;<span class="ref-vol">158A</span>:732–42.</span> [<a href="/pmc/articles/PMC4264531/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4264531</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22383261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22383261</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.dowling.2003.957">Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, Kayserili H, Yuksel-Apak M, Paller AS, Norton K, Teebi AS, Grum-Tokars V, Martin GS, Davis GE, Glucksman MJ, Martignetti JA. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. <span><span class="ref-journal">Am J Hum Genet. </span>2003;<span class="ref-vol">73</span>:957–66.</span> [<a href="/pmc/articles/PMC1180616/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1180616</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12973667" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12973667</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.elkamah.2010.213">El-Kamah GY, Fong K, El-Ruby M, Afifi HH, Clements SE, Lai-Cheong JE, Amr K, El-Darouti M, McGrath JA. Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis. <span><span class="ref-journal">Br J Dermatol. </span>2010;<span class="ref-vol">163</span>:213–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20331448" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20331448</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.elkamah.2009.6">El-Kamah GY, Mostafa MI. 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Protein-losing enteropathy and joint contractures caused by a novel homozygous ANTXR2 mutation. <span><span class="ref-journal">Adv Genomics Genet. </span>2018;<span class="ref-vol">8</span>:17–21.</span> [<a href="/pmc/articles/PMC6057141/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6057141</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30050362" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30050362</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.shieh.2006.e1485">Shieh JTC, Swidler P, Martignetti JA, Ramirez MC, Balboni I, Kaplan J, Kennedy J, Abdul-Rahman O, Enns GM, Sandborg C, Slavotinek A, Hoyme HE. 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A case of bullous pemphigoid arising in juvenile hyaline fibromatosis with oral squamous cell carcinoma. <span><span class="ref-journal">J Dermatol. </span>2005;<span class="ref-vol">32</span>:650–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16334866" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16334866</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="sys-h.REF.unger.2023.1164">Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. 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Skeletal muscle involvement in infantile systemic hyalinosis. <span><span class="ref-journal">Eur J Paediatr Neurol. </span>2003;<span class="ref-vol">7</span>:401–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14623219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14623219</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1525_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Joseph TC Shieh</span>, MD, PhD<div class="affiliation small">Division of Medical Genetics<br />Department of Pediatrics<br />Institute for Human Genetics<br />University of California San Francisco<br />San Francisco, California<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.fscu@2heihs.hpesoj" class="oemail">ude.fscu@2heihs.hpesoj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">H Eugene Hoyme</span>, MD<div class="affiliation small">Department of Pediatrics<br />Sanford School of Medicine<br />University of South Dakota;<br />Sanford Children's Hospital<br />Sioux Falls, South Dakota</div></div><div class="contrib half_rhythm"><span itemprop="author">Laura T Arbour</span>, MD<div class="affiliation small">Department of Medical Genetics<br />Island Medical Program<br />University of British Columbia<br />Victoria, British Columbia, Canada</div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">February 27, 2008</span>; Last Revision: <span itemprop="dateModified">May 11, 2023</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Shieh JTC, Hoyme HE, Arbour LT. Hyaline Fibromatosis Syndrome. 2008 Feb 27 [Updated 2023 May 11]. 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/hgps/?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/hyper-pp/?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="figobsyshTmoleculargenetictestingusedi"><div id="sys-h.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.molecular_genetic_testing_used_i_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_sys-h.T.molecular_genetic_testing_used_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_sys-h.T.molecular_genetic_testing_used_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_sys-h.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ANTXR2</i>
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</td><td headers="hd_h_sys-h.T.molecular_genetic_testing_used_i_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_sys-h.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">95% <sup>4</sup></td></tr><tr><td headers="hd_h_sys-h.T.molecular_genetic_testing_used_i_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_sys-h.T.molecular_genetic_testing_used_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~5% <sup>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="sys-h.TF.1.1"><p class="no_margin">See <a href="/books/NBK1525/?report=reader#sys-h.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="sys-h.TF.1.2"><p class="no_margin">See <a href="#sys-h.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="sys-h.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="sys-h.TF.1.4"><p class="no_margin"><a class="bibr" href="#sys-h.REF.dowling.2003.957" rid="sys-h.REF.dowling.2003.957">Dowling et al [2003]</a>, <a class="bibr" href="#sys-h.REF.hanks.2003.791" rid="sys-h.REF.hanks.2003.791">Hanks et al [2003]</a>, <a class="bibr" href="#sys-h.REF.elkamah.2010.213" rid="sys-h.REF.elkamah.2010.213">El-Kamah et al [2010]</a>, <a class="bibr" href="#sys-h.REF.denadai.2012.732" rid="sys-h.REF.denadai.2012.732">Denadai et al [2012]</a>, <a class="bibr" href="#sys-h.REF.casasalba.2018.1752" rid="sys-h.REF.casasalba.2018.1752">Casas-Alba et al [2018]</a>, <a class="bibr" href="#sys-h.REF.cozma.2019.209" rid="sys-h.REF.cozma.2019.209">Cozma et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="sys-h.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="sys-h.TF.1.6"><p class="no_margin"><a class="bibr" href="#sys-h.REF.shieh.2006.e1485" rid="sys-h.REF.shieh.2006.e1485">Shieh et al [2006]</a>, <a class="bibr" href="#sys-h.REF.denadai.2012.732" rid="sys-h.REF.denadai.2012.732">Denadai et al [2012]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshTfeaturesofhyalinefibromatosis"><div id="sys-h.T.features_of_hyaline_fibromatosis" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Features of Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.features_of_hyaline_fibromatosis/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.features_of_hyaline_fibromatosis_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin nodules</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>80%</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Can be diagnostic</td></tr><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hyperpigmented skin over bony prominences, thickened skin</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Can be diagnostic</td></tr><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Contractures</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~60%</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable depending on severity</td></tr><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gingival enlargement</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">93%</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Protein-losing enteropathy</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diarrhea, reported in >50%, is likely more common than reported.</td></tr><tr><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Immunodeficiency</b>
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</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~33%</td><td headers="hd_h_sys-h.T.features_of_hyaline_fibromatosis_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable; may be underreported.</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="sys-h.TF.2.1"><p class="no_margin">Presence of findings may be age dependent.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshTothergenesandconditionsofin"><div id="sys-h.T.other_genes_and_conditions_of_in" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Other Genes and Conditions of Interest in the Differential Diagnosis of Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.other_genes_and_conditions_of_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.other_genes_and_conditions_of_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of DiffDx Disorder</th></tr><tr><th headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4" id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/HFS</th><th headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4" id="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Differentiating from HFS</th></tr></thead><tbody><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ASAH1</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Farber disease (See <a href="/books/n/gene/asah1/?report=reader"><i>ASAH1</i> Disorders</a>.)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typically presents w/painful joint contractures & progressive hoarseness; skin nodules develop, esp over bony prominences.</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic involvement in most persons; absence of hyperpigmented patches</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>COL1A1</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/caffey/?report=reader">Caffey disease</a> (infantile cortical hyperostosis)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents w/irritability, poor feeding, fever, & soft tissue swelling</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Characteristic radiographic hyperostoses</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ECM1</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/lipoid-p/?report=reader">Lipoid proteinosis</a>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents w/hoarseness, followed by development of papules around eyelids</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Facial papules, tongue enlargement, dental hypoplasia, & distinct skin lesions (vesicles & crusted bullae evolving into waxy plaques)</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FBN1</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Stiff skin syndrome (OMIM <a href="https://omim.org/entry/184900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">184900</a>)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Thickened skin & flexion contractures; mucopolysaccharide deposition has been found in the skin but mucopolysacchariduria has not been detected.</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_2" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">Absence of characteristic HFS skin findings</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GNPTAB</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mucolipidosis II (See <a href="/books/n/gene/ml2/?report=reader"><i>GNPTAB</i> Disorders</a>.)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gingival thickening & dysostosis multiplex; facies are coarse & joint contractures develop over time.</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Mucolipidosis IIIα/β (See <a href="/books/n/gene/ml2/?report=reader"><i>GNPTAB</i> Disorders</a>.)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotype varies in severity; principal features: contractures & dysostosis multiplex.</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>MMP2</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/mona/?report=reader">Multicentric osteolysis nodulosis & arthropathy</a> <sup>1</sup></td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature & osteolysis of interphalangeal & metacarpal-phalangeal joints</td></tr><tr><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>PDGFRB</i>
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</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital generalized fibromatosis (OMIM <a href="https://omim.org/entry/228550" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">228550</a>)</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_1_4 hd_h_sys-h.T.other_genes_and_conditions_of_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Solitary, multiple, or generalized nodules composed of cells w/features of differentiated fibroblasts & smooth muscle cells</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; HFS = hyaline fibromatosis syndrome; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sys-h.TF.3.1"><p class="no_margin">In addition to multicentric osteolysis nodulosis and arthropathy (MONA), this phenotype has been reported in the literature as Torg syndrome, Winchester-Torg (or Torg-Winchester) syndrome, and nodulosis-arthropathy-osteolysis (NAO) syndrome. All of these conditions have been shown to be caused by biallelic pathogenic variants in <i>MMP2</i> with no discernible genotype-phenotype correlation.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshTrecommendedevaluationsfollowin"><div id="sys-h.T.recommended_evaluations_followin" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.recommended_evaluations_followin/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.recommended_evaluations_followin_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sys-h.T.recommended_evaluations_followin_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_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>GI/Nutrition</b>
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</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete GI & nutritional eval</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl eval for intestinal malabsorption & protein-losing enteropathy</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider pain management eval, orthopedic eval.</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For contractures</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Immunologic</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider immunology eval.</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for immune deficiency both cellular & humoral; protein-losing enteropathy</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiac</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider echocardiogram.</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate cardiac function</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Endocrine</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider endocrine eval.</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Possible osteopenia, recurrent fractures</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Dental</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider dental eval.</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For gingival hypertrophy & dental abnormalities</td></tr><tr><td headers="hd_h_sys-h.T.recommended_evaluations_followin_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
|
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<br />
|
|
<b>counseling</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_evaluations_followin_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_sys-h.T.recommended_evaluations_followin_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 HFS in order to facilitate medical & personal decision-making</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal; HFS = hyaline fibromatosis syndrome; MOI= mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="sys-h.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="figobsyshTtreatmentofmanifestationsini"><div id="sys-h.T.treatment_of_manifestations_in_i" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.treatment_of_manifestations_in_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.treatment_of_manifestations_in_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_sys-h.T.treatment_of_manifestations_in_i_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_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Failure to thriv</b>
|
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</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Early consideration of nasogastric tube or gastrostomy tube feeding or parenteral nutrition</div></li><li class="half_rhythm"><div>Nutrition should be tailored for possibility of malabsorption or lymphangiectasia.</div></li></ul>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<p>A nutritionist should follow affected persons.</p>
|
|
</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Protein-losing enteropathy</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Diarrhea & protein-losing enteropathy w/subsequent edema should be treated w/hydration & albumin infusions.</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">An effective long-term treatment is lacking; the effectiveness of dietary therapies w/intestinal lymphangiectasia is not known.</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Joint contractures</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PT assessment</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">When passive movement of joint contractures is painful, PT should be carried out w/care; in some cases PT is not tolerated because of pain.</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Pain</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nonsteroidal anti-inflammatory drugs & opiates</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Agents such as gabapentin should also be considered.</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Gentle handling may ↓ pain that is worsened w/movement.</div></li><li class="half_rhythm"><div>Splinting of affected joints may provide comfort.</div></li></ul>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consultation w/a pain mgmt specialist may be helpful.</div></li><li class="half_rhythm"><div>Palliative care consultation may be an option in severe cases.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Skin nodules, gingival thickening, & lesions of the mouth</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Surgical excision is an option.</div></li><li class="half_rhythm"><div>Anesthesiologists should be aware of difficulty of endotracheal intubation & mgmt in some affected persons [<a class="bibr" href="#sys-h.REF.pollard.2008.1123" rid="sys-h.REF.pollard.2008.1123">Pollard et al 2008</a>, <a class="bibr" href="#sys-h.REF.qasem.2012.263" rid="sys-h.REF.qasem.2012.263">Qasem et al 2012</a>].</div></li></ul>
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|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lesions may recur after excision.</div></li><li class="half_rhythm"><div>Significant complication w/anesthesia has been reported [<a class="bibr" href="#sys-h.REF.elkamah.2009.6" rid="sys-h.REF.elkamah.2009.6">El-Kamah & Mostafa 2009</a>].</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Perianal masses</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical excision is possible.</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Masses may recur after excision.</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Skin nodules</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dermatology eval</div></li><li class="half_rhythm"><div>Plastic surgery eval</div></li></ul>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intertriginous, perianal, & neck areas are prone to masses / hypertrophic skin lesions.</td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Immune deficiency</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Treatment of infection based on site & causative agent</div></li><li class="half_rhythm"><div>Consider humoral & cellular immune workup.</div></li></ul>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Psychosocial</b>
|
|
</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider family counseling.</td><td headers="hd_h_sys-h.T.treatment_of_manifestations_in_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To develop coping strategies for affected person & family</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">PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshTrecommendedsurveillanceforind"><div id="sys-h.T.recommended_surveillance_for_ind" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Hyaline Fibromatosis Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.T.recommended_surveillance_for_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.T.recommended_surveillance_for_ind_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_sys-h.T.recommended_surveillance_for_ind_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_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Gastrointestinal/</b>
|
|
<br />
|
|
<b>Nutrition</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Assessment of antibody levels, albumin</div></li><li class="half_rhythm"><div>Assessment for GI malabsorption</div></li><li class="half_rhythm"><div>Nutrition assessment</div></li></ul>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_3" rowspan="6" colspan="1" style="text-align:left;vertical-align:middle;">As needed based on clinical presentation</td></tr><tr><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical history & exam for contracture progression & pain</td></tr><tr><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Integument</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam for concerning lesions</td></tr><tr><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Immune system</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of antibody levels</td></tr><tr><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>ENT/Dental</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam for oral lesions affecting feeding/nutrition & → dental complications</td></tr><tr><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cardiology</b>
|
|
</td><td headers="hd_h_sys-h.T.recommended_surveillance_for_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cardiac assessment</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">GI = gastrointestinal</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshmolgenTA"><div id="sys-h.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Hyaline Fibromatosis Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1525/table/sys-h.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_sys-h.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_sys-h.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_sys-h.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_sys-h.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_sys-h.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_sys-h.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_sys-h.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/118429" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ANTXR2</i>
|
|
</a>
|
|
</td><td headers="hd_b_sys-h.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=118429" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">4q21<wbr style="display:inline-block"></wbr>​.21</a>
|
|
</td><td headers="hd_b_sys-h.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P58335" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Anthrax toxin receptor 2</a>
|
|
</td><td headers="hd_b_sys-h.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ANTXR2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ANTXR2 database</a>
|
|
</td><td headers="hd_b_sys-h.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ANTXR2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ANTXR2</a>
|
|
</td><td headers="hd_b_sys-h.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ANTXR2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ANTXR2</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="sys-h.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobsyshmolgenTB"><div id="sys-h.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Hyaline Fibromatosis Syndrome (<a href="/omim/228600,608041" 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/NBK1525/table/sys-h.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__sys-h.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/228600" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">228600</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HYALINE FIBROMATOSIS SYNDROME; HFS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/608041" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608041</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ANTHRAX TOXIN RECEPTOR 2; ANTXR2</td></tr></tbody></table></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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