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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Type II Collagen Disorders Overview - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Type II Collagen Disorders Overview">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2024/10/24">
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<meta name="citation_author" content="Pernille Axél Gregersen">
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<meta name="citation_author" content="Ravi Savarirayan">
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<meta name="citation_keywords" content="Achondrogenesis Type II">
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<meta name="citation_keywords" content="Stickler Syndrome Type 1">
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<meta name="citation_keywords" content="Kniest Dysplasia">
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<meta name="citation_keywords" content="Spondyloepiphyseal Dysplasia Congenita (SEDC)">
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<meta name="citation_keywords" content="Platyspondylic Dysplasia, Torrance Type">
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<meta name="citation_keywords" content="Spondyloperipheral Dysplasia">
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<meta name="citation_keywords" content="Spondyloepimetaphyseal Dysplasia (SEMD), Strudwick Type">
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<meta name="citation_keywords" content="Hypochondrogenesis">
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<meta name="citation_keywords" content="Spondyloepiphyseal Dysplasia with Metatarsal shortening">
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<meta name="citation_keywords" content="Collagen alpha-1(II) chain">
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<meta name="citation_keywords" content="COL2A1">
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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="_NBK540447_"><span class="title" itemprop="name">Type II Collagen Disorders Overview</span></h1><p class="contribs">Gregersen PA, Savarirayan R.</p><p class="fm-aai"><a href="#_NBK540447_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 30 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="collagen-2.Summary" itemprop="description"><h2 id="_collagen-2_Summary_">Summary</h2><p>The purpose of this <i>GeneReview</i> is to:</p><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">Describe the <a href="#collagen-2.Clinical_Characteristics_of_T">clinical characteristics</a> of type II collagen disorders;</p></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><p class="no_top_margin">Provide an <a href="#collagen-2.Evaluation_Strategies_to_Iden">evaluation strategy</a> to identify the genetic cause of a type II collagen disorder in a proband;</p></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><p class="no_top_margin">Review the <a href="#collagen-2.Differential_Diagnosis_of_Typ">differential diagnosis</a> of type II collagen disorders with a focus on genetic conditions;</p></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><p class="no_top_margin">Review <a href="#collagen-2.Management">management</a> of type II collagen disorders;</p></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><p class="no_top_margin">Inform <a href="#collagen-2.Genetic_Counseling">genetic counseling</a> of family members of an individual with a type II collagen disorder.</p></dd></dl></dl>
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</div><div id="collagen-2.Clinical_Characteristics_of_T"><h2 id="_collagen-2_Clinical_Characteristics_of_T_">1. Clinical Characteristics of Type II Collagen Disorders</h2><div id="collagen-2.Clinical_Description"><h3>Clinical Description</h3><p>Type II collagen is an essential component of the cartilage extracellular matrix, and of major importance in endochondral bone formation, growth, and normal joint function. It is also necessary for normal development and function of the eye and the inner ear. Type II collagen disorders encompass a diverse group of clinical phenotypes characterized by skeletal dysplasia, ocular manifestations (e.g., cataract, myopia, subluxation of the lens, vitreous abnormalities, retinal detachment), hearing impairment, and orofacial features [<a class="bibr" href="#collagen-2.REF.nishimura.2005.36" rid="collagen-2.REF.nishimura.2005.36">Nishimura et al 2005</a>, <a class="bibr" href="#collagen-2.REF.kannu.2012.e38" rid="collagen-2.REF.kannu.2012.e38">Kannu et al 2012</a>, <a class="bibr" href="#collagen-2.REF.spranger.a" rid="collagen-2.REF.spranger.a">Spranger et al 2012a</a>, <a class="bibr" href="#collagen-2.REF.terhal.2015.461" rid="collagen-2.REF.terhal.2015.461">Terhal et al 2015</a>, <a class="bibr" href="#collagen-2.REF.savarirayan.2019.2070" rid="collagen-2.REF.savarirayan.2019.2070">Savarirayan et al 2019</a>].</p><p>The spectrum of severity ranges from severe perinatal-lethal disorders to milder conditions presenting in adulthood with premature arthrosis as the primary feature. Considerable phenotypic overlap notwithstanding, discriminating features can aid in the specific diagnosis (see <a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" rid-ob="figobcollagen2Tclinicalandradiographicf">Table 1</a>). The following individual phenotypes are recognized in the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bibr" href="#collagen-2.REF.unger.2023.1164" rid="collagen-2.REF.unger.2023.1164">Unger et al 2023</a>], and can be grouped according to severity.</p><p>
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<b>Most severe (often lethal perinatally)</b>
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</p><ul><li class="half_rhythm"><div>Achondrogenesis, <i>COL2A1</i>-related (formerly type II, type Langer-Saldino)</div></li><li class="half_rhythm"><div>Hypochondrogenesis, <i>COL2A1</i>-related</div></li><li class="half_rhythm"><div>Platyspondylic dysplasia, type Torrance, <i>COL2A1</i>-related</div></li></ul><p>
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<b>Severe / moderately severe (neonatal presentation)</b>
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</p><ul><li class="half_rhythm"><div>Kniest dysplasia, <i>COL2A1</i>-related</div></li><li class="half_rhythm"><div>Spondyloepiphyseal dysplasia congenita (SEDC), <i>COL2A1</i>-related</div></li><li class="half_rhythm"><div>Spondyloepimetaphyseal dysplasia (SEMD), <i>COL2A1</i>-related</div></li></ul><p>
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<b>Intermediate (neonatal/childhood/adolescent presentation)</b>
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</p><ul><li class="half_rhythm"><div>Spondyloperipheral dysplasia, <i>COL2A1</i>-related</div></li><li class="half_rhythm"><div>Spondyloepiphyseal dysplasia (SED) with metatarsal shortening, <i>COL2A1</i>-related</div></li><li class="half_rhythm"><div>Stickler syndrome, <i>COL2A1</i>-related</div></li></ul><p>
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<b>Mild (adolescent/adult presentation)</b>
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</p><ul><li class="half_rhythm"><div>Mild spondyloepiphyseal dysplasia (SED) with premature arthrosis</div></li></ul><div id="collagen-2.Most_Severe_often_lethal_peri"><h4>Most Severe (often lethal perinatally)</h4><p><b>Achondrogenesis, <i>COL2A1</i>-related,</b> is the most severe type II collagen disorder. Achondrogenesis, <i>COL2A1-</i>related, usually presents in the prenatal setting with short stature, extremely short limbs (micromelia), narrow chest with pulmonary hypoplasia, extraskeletal features (e.g., flat midface, Pierre Robin sequence [PRS]), and edema/hydropic appearance. Radiographic findings include poor ossification of the axial skeleton, absent or delayed ossification of the vertebral bodies, absent ossification of the sacrum, and absent or severely delayed ossification of pubic and ischial bones. Iliac bones are small with crescent-shaped inner and inferior margins. The distal femora and proximal tibiae show delayed ossification, and the ribs and tubular bones are short. The majority of these infants do not survive to term, and are often delivered prematurely, are stillborn, or die shortly after birth as a result of cardiorespiratory failure [<a class="bibr" href="#collagen-2.REF.spranger.b" rid="collagen-2.REF.spranger.b">Spranger et al 2012b</a>].</p><p><b>Hypochondrogenesis, <i>COL2A1</i>-related,</b> is characterized by short limbs, small thorax, flat facial profile, PRS, and delayed skeletal ossification, but with less severe clinical course and skeletal involvement than achondrogenesis, <i>COL2A1-</i>related. Vertebral bodies are small and ovoid, and unossified in the cervical region. The pubic bones are unossified and the ilia are hypoplastic. There is shortening of the long bones and delayed ossification in distal femoral and proximal tibial epiphyseal ossification centers. Infants with hypochondrogenesis have a short survival span ranging from days to months [<a class="bibr" href="#collagen-2.REF.castori.2006.460" rid="collagen-2.REF.castori.2006.460">Castori et al 2006</a>].</p><p>Note: Achondrogenesis, <i>COL2A1</i>-related, and hypochondrogenesis, <i>COL2A1</i>-related, form one phenotypic continuum.</p><p><b>Platyspondylic dysplasia, type Torrance, <i>COL2A1</i>-related,</b> is characterized by disproportionate short stature, short limbs, and coarse facial features. Skeletal findings consist of very thin vertebral bodies (severe platyspondyly), incomplete vertebral ossification, short ribs and narrow chest, short long bones with delayed/poor ossification, and splayed metaphyses of ribs and long bones. The majority of infants die at or shortly after birth; however, individuals with long-term survival have been reported [<a class="bibr" href="#collagen-2.REF.nishimura.2004.75" rid="collagen-2.REF.nishimura.2004.75">Nishimura et al 2004</a>, <a class="bibr" href="#collagen-2.REF.spranger.e" rid="collagen-2.REF.spranger.e">Spranger et al 2012e</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p></div><div id="collagen-2.Severe__Moderately_Severe_neo"><h4>Severe / Moderately Severe (neonatal presentation)</h4><p><b>Kniest dysplasia, <i>COL2A1</i>-related,</b> is a very severe type II collagen disorder, but results in live birth and longer survival. The clinical presentation is characterized by severe disproportionate short stature, short neck, short thorax, short extremities, and distinct ocular findings: myopia, vitreal abnormalities, and retinal detachment. Radiographically, Kniest dysplasia, <i>COL2A1-</i>related, presents with pronounced abnormalities of bone modeling including platyspondyly with anterior wedging and coronal clefting of the lumbar vertebral bodies, delayed ossification in distal femoral and proximal tibial epiphyseal ossification centers, and short long bones with large metaphyses and epiphyses (dumbbell-type deformity of the long bones). Significant medical complications can occur mainly as a result of hypoplasia of the dens leading to cervical instability and spinal cord compression, tracheolaryngomalacia and related respiratory complications, and early-onset arthrosis [<a class="bibr" href="#collagen-2.REF.yazici.2010.348" rid="collagen-2.REF.yazici.2010.348">Yazici et al 2010</a>, <a class="bibr" href="#collagen-2.REF.spranger.c" rid="collagen-2.REF.spranger.c">Spranger et al 2012c</a>, <a class="bibr" href="#collagen-2.REF.sergouniotis.2015.475" rid="collagen-2.REF.sergouniotis.2015.475">Sergouniotis et al 2015</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p><p><b>Spondyloepiphyseal dysplasia congenita (SEDC), <i>COL2A1</i>-related.</b> Individuals with SEDC, <i>COL2A1-</i>related, present neonatally with severe disproportionate short stature, short extremities (<5th centile), characteristic facial features (hypertelorism, flat profile, PRS), myopia, and hearing loss. Radiographs display delayed/poor ossification of the vertebrae and the pubic bones, and the long bones are short with hypoplastic epiphyses. There is an increased risk for cervical instability and spinal cord compression (as seen in Kniest dysplasia, <i>COL2A1-</i>related), and individuals with SEDC, <i>COL2A1-</i>related, are also at greater risk for tracheolaryngomalacia and related respiratory complications.</p><p>SEDC, <i>COL2A1-</i>related, cannot be distinguished from spondyloepimetaphyseal dysplasia, <i>COL2A1</i>-related, until later in the first year of life, since metaphyseal dysplasia in the latter is not present at birth [<a class="bibr" href="#collagen-2.REF.spranger.d" rid="collagen-2.REF.spranger.d">Spranger et al 2012d</a>, <a class="bibr" href="#collagen-2.REF.terhal.2015.461" rid="collagen-2.REF.terhal.2015.461">Terhal et al 2015</a>].</p><p><b>Spondyloepimetaphyseal dysplasia (SEMD), <i>COL2A1</i>-related.</b> Infants with SEMD, <i>COL2A1-</i>related, initially present with the same clinical and radiographic findings as those with SEDC, <i>COL2A1-</i>related. However, within the first year of life, metaphyseal flaring becomes evident, suggesting the diagnosis of SEMD, <i>COL2A1</i>-related. The clinical course is similar to that of SEDC, <i>COL2A1-</i>related, with increased risk for cervical instability and spinal cord compression posing the greatest risk for these individuals [<a class="bibr" href="#collagen-2.REF.walter.2007.161" rid="collagen-2.REF.walter.2007.161">Walter et al 2007</a>, <a class="bibr" href="#collagen-2.REF.terhal.2015.461" rid="collagen-2.REF.terhal.2015.461">Terhal et al 2015</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p></div><div id="collagen-2.Intermediate_neonatalchildhoo"><h4>Intermediate (neonatal/childhood/adolescent presentation)</h4><p><b>Spondyloperipheral dysplasia, <i>COL2A1</i>-related,</b> is characterized by mild-to-moderate disproportionate short stature and short extremities, brachydactyly type E, short ulnae, variable clubfeet, cleft palate, myopia, and hearing loss. Radiographs show ovoid vertebra, delayed ossification of pubic bones, and flattened and irregular epiphyses in the long bones in addition to the brachydactyly and short ulnae. Premature hip arthrosis causes joint pain [<a class="bibr" href="#collagen-2.REF.zankl.2004.144" rid="collagen-2.REF.zankl.2004.144">Zankl et al 2004</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p><p><b>Spondyloepiphyseal dysplasia (SED) with metatarsal shortening, <i>COL2A1</i>-related,</b> is characterized by severe joint pain in the lower limbs before adolescence and shortening of the postaxial toes (usually the 3rd and/or 4th toes). Height is average, and ocular and orofacial abnormalities are absent. Radiographs are characterized by mild platyspondyly with irregular end plates, narrowed intervertebral spaces, signs of osteoarthrosis including deformed femoral heads and dysplastic pelvis with irregular acetabulae, and shortening of the metatarsal and metacarpal bones [<a class="bibr" href="#collagen-2.REF.kozlowski.2004.87" rid="collagen-2.REF.kozlowski.2004.87">Kozlowski et al 2004</a>, <a class="bibr" href="#collagen-2.REF.marik.2004.157" rid="collagen-2.REF.marik.2004.157">Marik et al 2004</a>, <a class="bibr" href="#collagen-2.REF.hoornaert.2007.1269" rid="collagen-2.REF.hoornaert.2007.1269">Hoornaert et al 2007</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p><p><b>Stickler syndrome, <i>COL2A1</i>-related,</b> is one of the milder and more frequent type II collagen disorders [<a class="bibr" href="#collagen-2.REF.barathouari.2016b.992" rid="collagen-2.REF.barathouari.2016b.992">Barat-Houari et al 2016b</a>, <a class="bibr" href="#collagen-2.REF.barathouari.2016c.7" rid="collagen-2.REF.barathouari.2016c.7">Barat-Houari et al 2016c</a>], and the most common type of <a href="/books/n/gene/stickler/?report=reader">Stickler syndrome</a>. It shows remarkable inter- and intrafamilial phenotypic variation, with severity ranging from involvement of many organs to milder phenotypes with only ocular manifestations and clinical and radiographic findings of early-onset osteoarthrosis. The ocular manifestations include high myopia, congenital membranous vitreous abnormalities (most often type 1 congenital vitreous anomaly or "membranous" vitreous phenotype), retinal detachment, and early-onset cataract. The orofacial abnormalities include flat facial profile (underdevelopment of the maxilla and nasal bridge), isolated small jaw, isolated cleft palate, or a combination (PRS), and hearing loss that can be conductive and/or sensorineural. The musculoskeletal manifestations include mild short stature or average stature, joint hypermobility, and skeletal dysplasia. Radiographic features include mild-to-moderate flattening of the vertebra with or without end plate irregularities, and irregular epiphyses of the long bones [<a class="bibr" href="#collagen-2.REF.szymkobennett.2001.1061" rid="collagen-2.REF.szymkobennett.2001.1061">Szymko-Bennett et al 2001</a>, <a class="bibr" href="#collagen-2.REF.liberfarb.2003.21" rid="collagen-2.REF.liberfarb.2003.21">Liberfarb et al 2003</a>, <a class="bibr" href="#collagen-2.REF.rose.2005.199" rid="collagen-2.REF.rose.2005.199">Rose et al 2005</a>, <a class="bibr" href="#collagen-2.REF.snead.2011.1389" rid="collagen-2.REF.snead.2011.1389">Snead et al 2011</a>, <a class="bibr" href="#collagen-2.REF.acke.2012.84" rid="collagen-2.REF.acke.2012.84">Acke et al 2012</a>]. Typically, phenotypic findings present in childhood or later, although micrognathia, cleft palate, and polyhydramnios have been detected on prenatal ultrasound [<a class="bibr" href="#collagen-2.REF.soulier.2002.567" rid="collagen-2.REF.soulier.2002.567">Soulier et al 2002</a>, <a class="bibr" href="#collagen-2.REF.pacella.2010.1051" rid="collagen-2.REF.pacella.2010.1051">Pacella et al 2010</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>].</p></div><div id="collagen-2.Mild_adolescentadult_presenta"><h4>Mild (adolescent/adult presentation)</h4><p><b>Mild spondyloepiphyseal dysplasia (SED) with premature-onset arthrosis</b> is the mildest form of type II collagen disorder. It is characterized clinically by progressive joint pain and limitation of motion of the hip and knee joints, and radiographically by epiphyseal dysplasia and early-onset osteoarthrosis. The manifestations are age dependent, and height, vision, hearing, and orofacial structures are usually normal [<a class="bibr" href="#collagen-2.REF.su.2008.1701" rid="collagen-2.REF.su.2008.1701">Su et al 2008</a>, <a class="bibr" href="#collagen-2.REF.kannu.2010.1421" rid="collagen-2.REF.kannu.2010.1421">Kannu et al 2010</a>, <a class="bibr" href="#collagen-2.REF.kannu.2011.1785" rid="collagen-2.REF.kannu.2011.1785">Kannu et al 2011</a>, <a class="bibr" href="#collagen-2.REF.handa.2021.192" rid="collagen-2.REF.handa.2021.192">Handa et al 2021</a>]. In the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bibr" href="#collagen-2.REF.unger.2023.1164" rid="collagen-2.REF.unger.2023.1164">Unger et al 2023</a>], mild SED with premature-onset arthrosis is included under SEDC, <i>COL2A1</i>-related.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Tclinicalandradiographicf"><a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobcollagen2Tclinicalandradiographicf"><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="collagen-2.T.clinical_and_radiographic_f"><a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" rid-ob="figobcollagen2Tclinicalandradiographicf">Table 1. </a></h4><p class="float-caption no_bottom_margin">Clinical and Radiographic Features of Type II Collagen Disorders from Most to Least Severe </p></div></div></div></div><div id="collagen-2.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>There is currently no clear genotype-phenotype correlation in type II collagen disorders, and there is significant phenotypic overlap. However, data do support some general rules [<a class="bibr" href="#collagen-2.REF.nishimura.2005.36" rid="collagen-2.REF.nishimura.2005.36">Nishimura et al 2005</a>, <a class="bibr" href="#collagen-2.REF.hoornaert.2006.406" rid="collagen-2.REF.hoornaert.2006.406">Hoornaert et al 2006</a>, <a class="bibr" href="#collagen-2.REF.terhal.2015.461" rid="collagen-2.REF.terhal.2015.461">Terhal et al 2015</a>, <a class="bibr" href="#collagen-2.REF.barathouari.2016b.992" rid="collagen-2.REF.barathouari.2016b.992">Barat-Houari et al 2016b</a>, <a class="bibr" href="#collagen-2.REF.barathouari.2016c.7" rid="collagen-2.REF.barathouari.2016c.7">Barat-Houari et al 2016c</a>] (see also <a href="https://databases.lovd.nl/shared/genes/COL2A1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Leiden Open Variation Database</a> [LOVD]). Most pathogenic <i>COL2A1</i> variants involve the triple helix domain.</p><ul><li class="half_rhythm"><div>Missense variants in the Gly position of the Gly-X-Y repeat motif cause substitution of glycine to a bulkier amino acid, interfering with triple helix formation. This dominant-negative effect is generally seen in the more severe <i>COL2A1</i>-related disorders (e.g., achondrogenesis; platyspondylic dysplasia, type Torrance; SEDC; and SEMD).</div></li><li class="half_rhythm"><div>In Kniest dysplasia, <i>COL2A1-</i>related, exon skipping is more common [<a class="bibr" href="#collagen-2.REF.barathouari.2016b.992" rid="collagen-2.REF.barathouari.2016b.992">Barat-Houari et al 2016b</a>, <a class="bibr" href="#collagen-2.REF.barathouari.2016c.7" rid="collagen-2.REF.barathouari.2016c.7">Barat-Houari et al 2016c</a>], and it appears that splicing variants impose a higher risk for ophthalmologic complications and hearing loss [<a class="bibr" href="#collagen-2.REF.terhal.2015.461" rid="collagen-2.REF.terhal.2015.461">Terhal et al 2015</a>].</div></li><li class="half_rhythm"><div>Arginine-to-cysteine substitutions are most often associated with non-lethal phenotypes [<a class="bibr" href="#collagen-2.REF.hoornaert.2006.406" rid="collagen-2.REF.hoornaert.2006.406">Hoornaert et al 2006</a>]. A p.Arg275Cys substitution in the Y position of the Gly-X-Y repeat motif causes SED with metatarsal shortening, <i>COL2A1-</i>related [<a class="bibr" href="#collagen-2.REF.hoornaert.2007.1269" rid="collagen-2.REF.hoornaert.2007.1269">Hoornaert et al 2007</a>].</div></li><li class="half_rhythm"><div>In Stickler syndrome, <i>COL2A1-</i>related, nonsense and frameshift variants dominate, introducing a premature termination codon leading to haploinsufficiency [<a class="bibr" href="#collagen-2.REF.richards.2006.696" rid="collagen-2.REF.richards.2006.696">Richards et al 2006</a>].</div></li></ul></div><div id="collagen-2.Penetrance"><h3>Penetrance</h3><p>Penetrance in type II collagen disorders is high, if not complete; only rare instances of apparently reduced penetrance have been reported [<a class="bibr" href="#collagen-2.REF.barathouari.2016b.992" rid="collagen-2.REF.barathouari.2016b.992">Barat-Houari et al 2016b</a>]. However, the milder disorders have age-dependent phenotypic manifestations, and wide inter- and intrafamilial phenotypic variation has been reported [<a class="bibr" href="#collagen-2.REF.liberfarb.2003.21" rid="collagen-2.REF.liberfarb.2003.21">Liberfarb et al 2003</a>, <a class="bibr" href="#collagen-2.REF.nakashima.2016.16007" rid="collagen-2.REF.nakashima.2016.16007">Nakashima et al 2016</a>]. At present, knowledge of underlying mechanisms is limited, but the phenotypic variation is likely caused by environmental factors and polymorphisms in disease-modifying genes and/or regulatory elements [<a class="bibr" href="#collagen-2.REF.bell.1997.174" rid="collagen-2.REF.bell.1997.174">Bell et al 1997</a>, <a class="bibr" href="#collagen-2.REF.bi.1999.85" rid="collagen-2.REF.bi.1999.85">Bi et al 1999</a>, <a class="bibr" href="#collagen-2.REF.liberfarb.2003.21" rid="collagen-2.REF.liberfarb.2003.21">Liberfarb et al 2003</a>, <a class="bibr" href="#collagen-2.REF.kannu.2010.1421" rid="collagen-2.REF.kannu.2010.1421">Kannu et al 2010</a>, <a class="bibr" href="#collagen-2.REF.nakashima.2016.16007" rid="collagen-2.REF.nakashima.2016.16007">Nakashima et al 2016</a>, <a class="bibr" href="#collagen-2.REF.yasuda.2017.528" rid="collagen-2.REF.yasuda.2017.528">Yasuda et al 2017</a>].</p></div><div id="collagen-2.Nomenclature"><h3>Nomenclature</h3><p>Achondrogenesis, <i>COL2A1</i>-related, was formerly known as achondrogenesis type II or achondrogenesis, type Langer-Saldino.</p><p>SED with metatarsal shortening, <i>COL2A1-</i>related, was formerly known as Czech dysplasia.</p></div><div id="collagen-2.Prevalence"><h3>Prevalence</h3><p>The exact prevalence of type II collagen disorders is not known. However, Stickler syndrome, <i>COL2A1</i>-related, may be the most common type II collagen disorder; the overall incidence of all types of Stickler syndrome is estimated at 1:10,000 [<a class="bibr" href="#collagen-2.REF.rose.2001.657" rid="collagen-2.REF.rose.2001.657">Rose et al 2001</a>].</p></div></div><div id="collagen-2.Evaluation_Strategies_to_Iden"><h2 id="_collagen-2_Evaluation_Strategies_to_Iden_">2. Evaluation Strategies to Identify the Genetic Cause of a Type II Collagen Disorder in a Proband</h2><p>Establishing a specific genetic cause of a type II collagen disorder:</p><ul><li class="half_rhythm"><div>Can aid in discussions of prognosis (which are beyond the scope of this <i>GeneReview</i>) and <a href="#collagen-2.Genetic_Counseling">genetic counseling</a>;</div></li><li class="half_rhythm"><div>Is based on clinical and radiologic findings and the identification of a pathogenic variant in <i>COL2A1</i>, and involves medical history, physical examination, radiographs, family history, and molecular genetic testing.</div></li><li class="half_rhythm"><div>Note: As no formal clinical diagnostic criteria exist, specific diagnosis should be confirmed by genetic testing.</div></li></ul><p><b>Medical history.</b> A type II collagen disorder should be suspected in a fetus or individual with classic disease hallmarks of short stature, skeletal dysplasia, ocular manifestations (early cataract, myopia, vitreous abnormalities, retinal detachment), small jaw, cleft palate (Pierre Robin sequence), flat midface, hearing impairment, joint hypermobility, and early-onset arthrosis (see <a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" rid-ob="figobcollagen2Tclinicalandradiographicf">Table 1</a>).</p><p><b>Physical examination.</b> A physical examination should include standard growth parameters (height, weight, head circumference) and address the following key issues: body proportions, craniofacial features (flat facial profile, hypertelorism, cleft palate, and retrognathia), spine, and joints (joint enlargement, hypermobility, contractures).</p><p><b>Imaging.</b> Specific radiographic findings are associated with each type II collagen disorder (see <a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" rid-ob="figobcollagen2Tclinicalandradiographicf">Table 1</a>).</p><p><b>Family history.</b> A three-generation family history should be taken, with attention to relatives with clinical and radiographic manifestations of type II collagen disorders (e.g., specific questions about cleft palate, joint pain/deterioration, sudden visual loss / retinal detachment, hearing loss). Relevant findings from direct examination or review of medical records (including results of molecular genetic testing) must be documented.</p><p><b>Molecular genetic testing</b> approaches can include <b>single-gene testing</b> and use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>COL2A1</i> detects missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis first. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications. Single-gene testing of <i>COL2A1</i> can be considered if clinical findings and/or family history indicate that pathogenic variants in <i>COL2A1</i> are most likely (see <a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object" rid-ob="figobcollagen2Tclinicalandradiographicf">Table 1</a>).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>COL2A1</i> and other genes of interest (see <a href="/books/NBK540447/table/collagen-2.T.disorders_with_known_geneti/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisorderswithknowngeneti">Table 2a</a> and <a href="/books/NBK540447/table/collagen-2.T.disorders_of_unknown_etiolo/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisordersofunknownetiolo">Table 2b</a>) should be considered, particularly in instances with diagnostic uncertainty (e.g., prenatal evaluations), 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) 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. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul></div><div id="collagen-2.Differential_Diagnosis_of_Typ"><h2 id="_collagen-2_Differential_Diagnosis_of_Typ_">3. Differential Diagnosis of Type II Collagen Disorders</h2><p>The differential diagnosis of type II collagen disorders includes a range of disorders, from severe often lethal skeletal dysplasia with abnormal ossification and major skeletal abnormalities to milder conditions with limited clinical and radiographic findings. Disorders with a known genetic etiology are listed in <a href="/books/NBK540447/table/collagen-2.T.disorders_with_known_geneti/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisorderswithknowngeneti">Table 2a</a>; disorders of unknown or multifactorial etiology are listed in <a href="/books/NBK540447/table/collagen-2.T.disorders_of_unknown_etiolo/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisordersofunknownetiolo">Table 2b</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Tdisorderswithknowngeneti"><a href="/books/NBK540447/table/collagen-2.T.disorders_with_known_geneti/?report=objectonly" target="object" title="Table 2a. " class="img_link icnblk_img" rid-ob="figobcollagen2Tdisorderswithknowngeneti"><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="collagen-2.T.disorders_with_known_geneti"><a href="/books/NBK540447/table/collagen-2.T.disorders_with_known_geneti/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisorderswithknowngeneti">Table 2a. </a></h4><p class="float-caption no_bottom_margin">Disorders with Known Genetic Etiology to Consider in the Differential Diagnosis of Type II Collagen Disorders </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Tdisordersofunknownetiolo"><a href="/books/NBK540447/table/collagen-2.T.disorders_of_unknown_etiolo/?report=objectonly" target="object" title="Table 2b. " class="img_link icnblk_img" rid-ob="figobcollagen2Tdisordersofunknownetiolo"><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="collagen-2.T.disorders_of_unknown_etiolo"><a href="/books/NBK540447/table/collagen-2.T.disorders_of_unknown_etiolo/?report=objectonly" target="object" rid-ob="figobcollagen2Tdisordersofunknownetiolo">Table 2b. </a></h4><p class="float-caption no_bottom_margin">Disorders of Unknown Etiology to Consider in the Differential Diagnosis of Type II Collagen Disorders </p></div></div></div><div id="collagen-2.Management"><h2 id="_collagen-2_Management_">4. Management</h2><p>Clinical practice guidelines for type II collagen disorders have been published [<a class="bibr" href="#collagen-2.REF.savarirayan.2019.2070" rid="collagen-2.REF.savarirayan.2019.2070">Savarirayan et al 2019</a>].</p><div id="collagen-2.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a type II collagen disorder, the evaluations summarized in <a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Ttypeiicollagendisorders"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobcollagen2Ttypeiicollagendisorders"><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="collagen-2.T.type_ii_collagen_disorders"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders">Table 3. </a></h4><p class="float-caption no_bottom_margin">Type II Collagen Disorders: Recommended Evaluations Following Initial Diagnosis </p></div></div></div><div id="collagen-2.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see <a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_1/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders1">Table 4</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Ttypeiicollagendisorders1"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_1/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobcollagen2Ttypeiicollagendisorders1"><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="collagen-2.T.type_ii_collagen_disorders_1"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_1/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders1">Table 4. </a></h4><p class="float-caption no_bottom_margin">Type II Collagen Disorders: Treatment of Manifestations </p></div></div></div><div id="collagen-2.Surveillance"><h3>Surveillance</h3><p>To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in <a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_2/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders2">Table 5</a> are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcollagen2Ttypeiicollagendisorders2"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_2/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobcollagen2Ttypeiicollagendisorders2"><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="collagen-2.T.type_ii_collagen_disorders_2"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_2/?report=objectonly" target="object" rid-ob="figobcollagen2Ttypeiicollagendisorders2">Table 5. </a></h4><p class="float-caption no_bottom_margin">Type II Collagen Disorders: Recommended Surveillance </p></div></div></div><div id="collagen-2.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>In individuals with cervical spine instability, extreme neck extension and neck flexion and contact sports should be avoided.</p><p>In case of general anesthesia, the cervical spine should be assessed by imaging prior to the procedure [<a class="bibr" href="#collagen-2.REF.white.2017.2584" rid="collagen-2.REF.white.2017.2584">White et al 2017</a>].</p></div><div id="collagen-2.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from recommended surveillance in order to avoid/prevent common complications.</p><p>See <a href="#collagen-2.Related_Genetic_Counseling_Is">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="collagen-2.Pregnancy_Management"><h3>Pregnancy Management</h3><p>In individuals with a small pelvis, delivery by cesarean section should be considered. However, each individual should be assessed by an obstetrician familiar with skeletal dysplasia [<a class="bibr" href="#collagen-2.REF.savarirayan.2018.545" rid="collagen-2.REF.savarirayan.2018.545">Savarirayan et al 2018</a>].</p></div><div id="collagen-2.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="collagen-2.Genetic_Counseling"><h2 id="_collagen-2_Genetic_Counseling_">5. 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="collagen-2.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Type II collagen disorders are typically inherited in an autosomal dominant manner.</p><p>Autosomal recessive inheritance of type II collagen disorders has been reported in several families to date [<a class="bibr" href="#collagen-2.REF.tham.2015.496" rid="collagen-2.REF.tham.2015.496">Tham et al 2015</a>, <a class="bibr" href="#collagen-2.REF.barathouari.2016a.263" rid="collagen-2.REF.barathouari.2016a.263">Barat-Houari et al 2016a</a>, <a class="bibr" href="#collagen-2.REF.alsannaa.2020.104059" rid="collagen-2.REF.alsannaa.2020.104059">Al-Sannaa et al 2020</a>, <a class="bibr" href="#collagen-2.REF.girisha.2020.338" rid="collagen-2.REF.girisha.2020.338">Girisha et al 2020</a>, <a class="bibr" href="#collagen-2.REF.zhang.2021.201" rid="collagen-2.REF.zhang.2021.201">Zhang et al 2021</a>, <a class="bibr" href="#collagen-2.REF.t_ys_z.2023.116614" rid="collagen-2.REF.t_ys_z.2023.116614">Tüysüz et al 2023</a>].</p></div><div id="collagen-2.Autosomal_Dominant_Inheritanc"><h3>Autosomal Dominant Inheritance – 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>Most individuals diagnosed with a severe type II collagen disorder have the disorder as the result of a <i>de novo</i> pathogenic variant. The overall proportion of individuals with a type II collagen disorder caused by a <i>de novo</i>
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<i>COL2A1</i> pathogenic variant is unknown.</div></li><li class="half_rhythm"><div>Many individuals diagnosed with a milder type II collagen disorder have an affected parent. Clinical variability within a family can be extensive; however, severe and mild forms are not seen in family members with the same pathogenic variant (i.e., the specific type II collagen diagnosis appears to run true in a family, but with variable expressivity).</div></li><li class="half_rhythm"><div>If the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing is recommended for the parents of the proband to evaluate their genetic status and inform recurrence risk assessment. Note: A proband may appear to be the only affected family member because of failure to recognize the disorder in mildly affected family members. Therefore, <i>de novo</i> occurrence of a <i>COL2A1</i> pathogenic variant in the proband cannot be confirmed unless molecular genetic testing has demonstrated that neither parent has the <i>COL2A1</i> pathogenic variant.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div class="half_rhythm">The proband has a <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div class="half_rhythm">The proband inherited a pathogenic variant from a parent with gonadal (or somatic and gonadal) mosaicism * [<a class="bibr" href="#collagen-2.REF.nagendran.2012.1204" rid="collagen-2.REF.nagendran.2012.1204">Nagendran et al 2012</a>, <a class="bibr" href="#collagen-2.REF.okamoto.2012.1953" rid="collagen-2.REF.okamoto.2012.1953">Okamoto et al 2012</a>, <a class="bibr" href="#collagen-2.REF.stevenson.2012.418" rid="collagen-2.REF.stevenson.2012.418">Stevenson et al 2012</a>, <a class="bibr" href="#collagen-2.REF.yamamoto.2020.454" rid="collagen-2.REF.yamamoto.2020.454">Yamamoto et al 2020</a>, <a class="bibr" href="#collagen-2.REF.morrison.2020.2191" rid="collagen-2.REF.morrison.2020.2191">Morrison et al 2020</a>]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.</div><div class="half_rhythm">* A parent with somatic and gonadal mosaicism for a <i>COL2A1</i> pathogenic variant may be mildly/minimally affected.</div></li></ul></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the <i>COL2A1</i> pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>Penetrance in type II collagen disorders is high; however, intrafamilial variability among heterozygous family members can be extensive. Note: Severe and mild forms are not seen in family members with the same pathogenic variant (i.e., the specific type II collagen diagnosis appears to run true in a family, but with variable expressivity).</div></li><li class="half_rhythm"><div>If the <i>COL2A1</i> pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental gonadal mosaicism [<a class="bibr" href="#collagen-2.REF.nagendran.2012.1204" rid="collagen-2.REF.nagendran.2012.1204">Nagendran et al 2012</a>, <a class="bibr" href="#collagen-2.REF.okamoto.2012.1953" rid="collagen-2.REF.okamoto.2012.1953">Okamoto et al 2012</a>, <a class="bibr" href="#collagen-2.REF.stevenson.2012.418" rid="collagen-2.REF.stevenson.2012.418">Stevenson et al 2012</a>, <a class="bibr" href="#collagen-2.REF.morrison.2020.2191" rid="collagen-2.REF.morrison.2020.2191">Morrison et al 2020</a>, <a class="bibr" href="#collagen-2.REF.yamamoto.2020.454" rid="collagen-2.REF.yamamoto.2020.454">Yamamoto et al 2020</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>COL2A1</i> pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for a type II collagen disorder because of the possibility of reduced penetrance in a heterozygous parent and the possibility of parental gonadal mosaicism.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Each child of an individual with a type II collagen disorder has a 50% chance of inheriting the <i>COL2A1</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Because many individuals with short stature have reproductive partners with short stature, offspring of individuals with a type II collagen disorder may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders. The phenotypes of these individuals are distinct from those of the parents, and the affected individuals may have serious sequelae and poor outcomes [<a class="bibr" href="#collagen-2.REF.unger.2001.140" rid="collagen-2.REF.unger.2001.140">Unger et al 2001</a>, <a class="bibr" href="#collagen-2.REF.flynn.2003.193" rid="collagen-2.REF.flynn.2003.193">Flynn & Pauli 2003</a>].</div></li></ul><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the pathogenic variant, the parent's family members may be at risk.</p></div><div id="collagen-2.Autosomal_Recessive_Inheritan"><h3>Autosomal Recessive Inheritance – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected individual are presumed to be heterozygous for a <i>COL2A1</i> pathogenic variant.</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 a <i>COL2A1</i> pathogenic variant and to allow reliable recurrence risk assessment.</div></li><li class="half_rhythm"><div>If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#collagen-2.REF.j_nsson.2017.519" rid="collagen-2.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>In the families described by <a class="bibr" href="#collagen-2.REF.tham.2015.496" rid="collagen-2.REF.tham.2015.496">Tham et al [2015]</a> and <a class="bibr" href="#collagen-2.REF.barathouari.2016a.263" rid="collagen-2.REF.barathouari.2016a.263">Barat-Houari et al [2016a]</a>, one heterozygous father presented with high myopia, asymmetric lower limbs, and average stature; one heterozygous mother was 154 cm tall; and the two other heterozygous parents were of normal stature.</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 a <i>COL2A1</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants.</div></li><li class="half_rhythm"><div>Heterozygous sibs are predicted to be either unaffected or mildly affected. Homozygous sibs will be affected in a manner similar to the affected individual but, because of variable expressivity, may have a more or less severe clinical outcome.</div></li></ul><p><b>Offspring of a proband.</b> Unless an affected individual's reproductive partner also has <i>COL2A1</i> pathogenic variant(s), the proband's offspring will be obligate heterozygotes for a pathogenic variant in <i>COL2A1.</i></p></div><div id="collagen-2.Related_Genetic_Counseling_Is"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#collagen-2.Evaluation_of_Relatives_at_Ri">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected.</div></li></ul></div><div id="collagen-2.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>COL2A1</i> pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="collagen-2.Resources"><h2 id="_collagen-2_Resources_">Resources</h2><p>
|
|
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
|
support organizations and/or registries for the benefit of individuals with this disorder
|
|
and their families. GeneReviews is not responsible for the information provided by other
|
|
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>MedlinePlus</b>
|
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</div><div>
|
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<a href="https://medlineplus.gov/genetics/gene/col2a1/#conditions" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COL2A1 gene</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>MedlinePlus</b>
|
|
</div><div>
|
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<a href="https://medlineplus.gov/genetics/condition/stickler-syndrome/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Stickler syndrome</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Stickler Involved People </b>
|
|
</div><div>
|
|
<a href="http://www.sticklers.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">sticklers.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Stickler Syndrome UK</b>
|
|
</div><div>United Kingdom</div><div><b>Phone:</b> 0800 066 8273</div><div><b>Email:</b> contact@stickler.org.uk</div><div>
|
|
<a href="http://www.stickler.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stickler.org.uk</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Little People of America</b>
|
|
</div><div><b>Phone:</b> 888-LPA-2001; 714-368-3689</div><div><b>Fax:</b> 707-721-1896</div><div><b>Email:</b> info@lpaonline.org</div><div>
|
|
<a href="https://www.lpaonline.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">lpaonline.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Little People UK</b>
|
|
</div><div>United Kingdom</div><div><b>Phone:</b> 07925893398</div><div><b>Email:</b> admin@littlepeopleuk.org</div><div>
|
|
<a href="http://littlepeopleuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">littlepeopleuk.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Short Statured People of Australia</b>
|
|
</div><div>Australia</div><div><b>Email:</b> info@sspa.org.au</div><div>
|
|
<a href="https://www.sspa.org.au/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">sspa.org.au</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Skeletal Dysplasia Management Consortium</b>
|
|
</div><div>
|
|
<a href="https://www.skeletaldysplasia.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">skeletaldysplasia.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>UCLA International Skeletal Dysplasia Registry (ISDR)</b>
|
|
</div><div><b>Phone:</b> 310-825-8998</div><div>
|
|
<a href="https://www.uclahealth.org/ortho/isdr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Skeletal Dysplasia Registry</a>
|
|
</div></li></ul>
|
|
</div><div id="collagen-2.Chapter_Notes"><h2 id="_collagen-2_Chapter_Notes_">Chapter Notes</h2><div id="collagen-2.Acknowledgments"><h3>Acknowledgments</h3><p>Dr Supriya Raj provided help with the tables, references, and proofreading.</p></div><div id="collagen-2.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>24 October 2024 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 April 2019 (sw) Review posted live</div></li><li class="half_rhythm"><div>22 January 2019 (rs) Original submission</div></li></ul></div></div><div id="collagen-2.References"><h2 id="_collagen-2_References_">References</h2><div id="collagen-2.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.acke.2012.84">Acke
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[<a href="https://pubmed.ncbi.nlm.nih.gov/28763154" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28763154</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.yamamoto.2020.454">Yamamoto
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K, Kubota
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T, Takeyari
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T, Miyata
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Parental somatogonadal COL2A1 mosaicism contributes to intrafamilial recurrence in a family with type 2 collagenopathy.
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Am J Med Genet A.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/31854518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31854518</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.yasuda.2017.528">Yasuda
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H, Oh
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JH. A novel regulatory mechanism of type II collagen expression via a SOX9-dependent enhancer in intron 6.
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[<a href="/pmc/articles/PMC5241729/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5241729</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27881681" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27881681</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.yazici.2010.348">Yazici
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Z, Kline-Fath
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BM, Laor
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BT. Fetal MR imaging of Kniest dysplasia.
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Pediatr Radiol.
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2010;40:348-52.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/20020120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20020120</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.zankl.2004.144">Zankl
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A, Zabel
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B, Hilbert
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K, Wildhardt
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G, Cuenot
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S, Xavier
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B, Ha-Vinh
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R, Bonafé
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L, Spranger
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J, Superti-Furga
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A. Spondyloperipheral dysplasia is caused by truncating mutations in the C-propeptide of COL2A1.
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Am J Med Genet A.
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2004;129A:144-8.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/15316962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15316962</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="collagen-2.REF.zhang.2021.201">Zhang
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Q, Yao
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R, Li
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Q, Li
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X, Feng
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B, Chang
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G, Wang
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J, Wang
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X.
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A novel homozygous variant of COL2A1 in a Chinese male with type II collagenopathy: a case report.
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BMC Med Genomics.
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2021;14:201.
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[<a href="/pmc/articles/PMC8359039/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8359039</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34380476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34380476</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK540447_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Pernille Axél Gregersen</span>, MD, PhD<div class="affiliation small">Department of Clinical Genetics;<br />Centre for Rare Diseases;<br />Pediatrics and Adolescent Medicine<br />Aarhus University Hospital<br />Aarhus, Denmark<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="kd.mr@gergnrep" class="oemail">kd.mr@gergnrep</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ravi Savarirayan</span>, MBBS, MD, FRACP, ARCPA (Hon)<div class="affiliation small">Victorian Clinical Genetics Service;<br />Murdoch Children's Research Institute;<br />University of Melbourne, Parkville<br />Melbourne, Australia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ua.gro.sgcv@nayariravas.ivar" class="oemail">ua.gro.sgcv@nayariravas.ivar</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">April 25, 2019</span>; Last Update: <span itemprop="dateModified">October 24, 2024</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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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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Washington) are included with each copy; (ii) a link to the original material is provided
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whenever the material is published elsewhere on the Web; and (iii) reproducers,
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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>Gregersen PA, Savarirayan R. Type II Collagen Disorders Overview. 2019 Apr 25 [Updated 2024 Oct 24]. 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/tubulin-ov/?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/thdrd/?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="figobcollagen2Tclinicalandradiographicf"><div id="collagen-2.T.clinical_and_radiographic_f" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Clinical and Radiographic Features of Type II Collagen Disorders from Most to Least Severe</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.clinical_and_radiographic_f/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.clinical_and_radiographic_f_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" style="text-align:left;vertical-align:middle;"><i>COL2A1</i>-Related Disorder</th><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" style="text-align:left;vertical-align:middle;">Age of<br />Diagnosis</th><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" style="text-align:left;vertical-align:middle;">Poor/<br />Delayed<br />Ossification</th><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" style="text-align:left;vertical-align:middle;">Stature</th><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" style="text-align:left;vertical-align:middle;">Extraskeletal<br />Abnormalities</th><th id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Distinguishing Feature(s) <sup>1</sup></th></tr><tr><th headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6" id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical</th><th headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6" id="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Radiographic</th></tr></thead><tbody><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" colspan="7" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Most severe (often lethal perinatally) <sup>2</sup></b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Achondrogenesis</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prenatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++++++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Extremely short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Flat midface; PRS; hydropic appearance</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Often delivered prematurely, stillborn, or die shortly after birth (hrs)</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absent or severely delayed ossification of vertebral bodies; short ribs; absent ossification of pubic bones, sacrum, & ischial & iliac bones (small w/crescent-shaped inner & inferior margins); very short tubular bones w/delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypochondrogenesis</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prenatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Extremely short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Flat midface; PRS</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Majority alive at birth, short survival (days to mos)</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poor/delayed ossification of axial skeleton; very short tubular bones in prenatal period; short ribs; vertebral bodies are small & ovoid, & unossified in cervical region; unossified pubic bones; hypoplastic ilia; short & relatively broad long bones w/delayed ossification in distal femoral & proximal tibial epiphysis</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Platyspondylic dysplasia, type Torrance</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prenatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Extremely short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Coarse facial features</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Majority alive at birth, short survival (days to mos)</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Platyspondyly; incomplete vertebral ossification; short ribs & narrow chest; splayed metaphyses of ribs & long bones</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" colspan="7" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Severe to moderately severe (neonatal presentation)</b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Kniest dysplasia</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Perinatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">PRS; high prevalence of myopia, lens subluxation, retinal detachment, & other vitreal abnormalities; ↑ risk of tracheolaryngomalacia</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most severe type II collagen disorder resulting in live birth; long-term joint problems; risk of cervical instability & myelopathy</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Platyspondyly w/anterior wedging in low thoracic & lumbar region; coronal cleft vertebral bodies; delayed ossification in distal femoral & proximal tibial epiphyseal ossification centers; dumbbell-type deformity of long bones (large metaphyses & epiphyses)</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SEDC</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Perinatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Flat facial profile, hypertelorism, PRS; ocular abnormalities; ↑ risk of tracheolaryngomalacia</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Severe disproportionate short stature/extremities (˂5th %ile); ↑ risk of cervical instability & spinal cord compression</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Delayed/absent ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; delayed carpal & tarsal ossification</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SEMD</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Perinatal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">Delayed ossification of pubic bones, spine, & distal femoral & proximal tibial epiphyseal ossification centers; metaphyseal dysplasia in 1st year of life (distinguishing SEMD, Strudwick type, from SEDC)</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" colspan="7" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Intermediate (neonatal/childhood/adolescent presentation)</b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Spondyloperipheral dysplasia</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Perinatal/infancy</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">++</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Myopia; hearing loss</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Moderate-to-mild disproportionate short stature; short extremities; brachydactyly; occasionally clubfeet</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ovoid vertebra & irregular epiphyses in long bones; brachydactyly type E; short ulnae</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SED w/metatarsal shortening</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Before adolescence</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Average</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Usually no extraskeletal abnormalities</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Typical phenotypic hallmark: shortening of 3rd & 4th toes; severe joint pain</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Platyspondyly w/irregular end plates; narrowed intervertebral spaces; early osteoarthrosis in spine & lower limb joints (deformed femoral heads & dysplastic pelvis); metatarsal hypoplasia involving postaxial toes</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Stickler syndrome</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable (typically perinatal if cleft palate)</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild short to average</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">High risk of high myopia, congenital membranous vitreous abnormalities, retinal detachment, & cataract; U-shaped cleft palate; auditory manifestations</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In case of PRS, diagnosis most often in infancy</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Radiographic appearance of precocious or inflammatory arthritis (childhood)</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" colspan="7" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Mild (adolescent/adult presentation)</b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild SED w/premature-onset arthrosis</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Adolescence/adulthood</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Average</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vision, hearing, & orofacial structures are usually normal.</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive joint pain & limitation of motion of hip & knee joint</td><td headers="hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_1_6 hd_h_collagen-2.T.clinical_and_radiographic_f_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Epiphyseal dysplasia & early-onset osteoarthrosis</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">PRS = Pierre Robin sequence; SED = spondyloepiphyseal dysplasia; SEDC = spondyloepiphyseal dysplasia congenita; SEMD = spondyloepimetaphyseal dysplasia</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="collagen-2.TF.1.1"><p class="no_margin">Features distinguishing this disorder from other type II collagen disorders</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="collagen-2.TF.1.2"><p class="no_margin">Can be very difficult to distinguish prenatally</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcollagen2Tdisorderswithknowngeneti"><div id="collagen-2.T.disorders_with_known_geneti" class="table"><h3><span class="label">Table 2a. </span></h3><div class="caption"><p>Disorders with Known Genetic Etiology to Consider in the Differential Diagnosis of Type II Collagen Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.disorders_with_known_geneti/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.disorders_with_known_geneti_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Disorder</th></tr><tr><th headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4" id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/type II collagen disorders</th><th headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4" id="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from type II collagen disorders</th></tr></thead><tbody><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Most severe <sup>1</sup></b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ALPL</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hops/?report=reader">Hypophosphatasia</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poor/delayed ossification</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence of ossification of skull & posterior elements of vertebrae; low serum ALP; no type II collagen extraskeletal characteristic abnormalities <sup>2</sup></td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>COL1A1</i><br /><i>COL1A2</i><br /><i>CRTAP</i><br /><i>P3H1</i> (<i>LEPRE1</i>)<br /><i>PPIB</i></td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe osteogenesis imperfecta (See <a href="/books/n/gene/oi/?report=reader"><i>COL1A1</i>/2 Osteogenesis Imperfecta</a>.)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poor/delayed ossification; short limbs</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple fractures & deformities of long bones; no type II collagen extraskeletal characteristic abnormalities <sup>2</sup></td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HSPG2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dyssegmental dysplasia (OMIM <a href="https://omim.org/entry/224410" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">224410</a>) (incl Silverman-Handmaker & Rolland-Desbuquois types)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Narrow chest; short limbs; cleft palate</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vertebral disorganization; marked differences in size & shape of vertebral bodies (anisospondyly); bowed long bones</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC26A2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/achon1b/?report=reader">Achondrogenesis type 1B</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poor ossification; flat face; short neck; hydropic appearance</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Crescent-shaped ilia; extremely short limbs w/loss of longitudinal orientation; short fingers & toes; hypoplasia of thorax; protuberant abdomen</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC26A2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ao2/?report=reader"><i>SLC26A2</i>-related atelosteogenesis</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Often delayed ossification of upper thoracic vertebra & pubic bone; short limbs; cleft palate; distinctive facial features (midface retrusion, depressed nasal bridge, micrognathia)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hitchhiker (abducted) thumbs; poor/delayed ossification less severe than in severe type II collagen disorders; distal tapering of humeri; hypoplastic fibulae</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC26A2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/diastrophic-d/?report=reader">Diastrophic dysplasia</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short limbs; spine & joint deformities</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hitchhiker thumbs/toes</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TRIP11</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Achondrogenesis, <i>TRIP11</i>-related (OMIM <a href="https://omim.org/entry/200600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">200600</a>)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poor/delayed ossification; hydropic appearance</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Poorly ossified skull bones; short, thin, easily fractured ribs; tubular bones more severely shortened & bowed</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Severe to moderately severe <sup>3</sup></b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>TRPV4</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Metatropic dysplasia<br />(See <a href="/books/n/gene/cmt2c/?report=reader">Autosomal Dominant <i>TRPV4</i> Disorders</a>.)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Limb shortening; spine & joint deformities</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Narrow transverse diameter of thorax; vertebral bodies diamond/oval shape; no coronal clefts; medially placed (inset) pedicles; more distal flaring in femur & proximal tibia; most often no facial, ophthalmic, or auditory abnormalities; <sup>2</sup> normal ossification of skeleton</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" colspan="5" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Intermediate severity <sup>4</sup></b>
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</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CCN6</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ppr-dysp/?report=reader">Progressive pseudorheumatoid dysplasia</a> (SED w/progressive arthropathy)</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Joint pain, multiple joint contractures, & prominent interphalangeal joints; short stature; moderate platyspondyly; widening of metaphyses; enlarged epiphyses; early osteoarthritis</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities; <sup>2</sup> toes distinct from SED w/metatarsal shortening <sup>5</sup></td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>COL9A1</i>
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<br />
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<i>COL9A2</i>
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<br />
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<i>COL9A3 COL11A1</i>
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<br />
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<i>COL11A2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/stickler/?report=reader">Stickler syndrome</a> types 2, 3, 4, & 5</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniofacial, ophthalmic, & auditory abnormalities; skeletal manifestations on radiographs (spondyloepiphyseal dysplasia) & joint involvement</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic complications often less severe than Stickler syndrome, <i>COL2A1</i>-related; ocular phenotypes in other Stickler types most often comprise type 2 congenital vitreous anomaly ("beaded" vitreous phenotype)</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>COL9A1</i>
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<br />
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<i>COL9A2</i>
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<br />
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<i>COL9A3</i>
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<br />
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<i>COMP</i>
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<br />
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<i>MATN3</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/edm-ad/?report=reader">Multiple epiphyseal dysplasia, autosomal dominant</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents in early childhood, usually w/pain in hips &/or knees</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities; <sup>2</sup> often no spine involvement</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SLC26A2</i>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/edm/?report=reader"><i>SLC26A2</i>-related multiple epiphyseal dysplasia</a>
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</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents in early childhood, usually w/pain in hips &/or knees; brachydactyly</td><td headers="hd_h_collagen-2.T.disorders_with_known_geneti_1_1_1_4 hd_h_collagen-2.T.disorders_with_known_geneti_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities; <sup>2</sup> clubfeet; cleft palate; double-layered patella observed on lateral knee radiographs in 60%; often no spine involvement</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; ALP = alkaline phosphatase; AR = autosomal recessive; MOI = mode of inheritance; SED = spondyloepiphyseal dysplasia</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="collagen-2.TF.2a.1"><p class="no_margin">The most severe type II collagen disorders include <i>COL2A1</i>-related achondrogenesis, hypochondrogenesis, and platyspondylic dysplasia, type Torrance. These disorders can be very difficult to distinguish prenatally.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="collagen-2.TF.2a.2"><p class="no_margin">Comprising characteristic type II collagen ocular, auditory, and orofacial abnormalities (i.e., high myopia, retinal detachment, hearing impairment, Pierre Robin sequence)</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="collagen-2.TF.2a.3"><p class="no_margin">Severe to moderately severe type II collagen disorders include <i>COL2A1</i>-related Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), and spondyloepimetaphyseal dysplasia (SEMD).</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="collagen-2.TF.2a.4"><p class="no_margin">Intermediate severity type II collagen disorders include <i>COL2A1</i>-related spondyloperipheral dysplasia, spondyloepiphyseal dysplasia (SED) with metatarsal shortening, and Stickler syndrome.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="collagen-2.TF.2a.5"><p class="no_margin">Shortening of the third and/or fourth toes is a classic distinguishing hallmark of SED with metatarsal shortening.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcollagen2Tdisordersofunknownetiolo"><div id="collagen-2.T.disorders_of_unknown_etiolo" class="table"><h3><span class="label">Table 2b. </span></h3><div class="caption"><p>Disorders of Unknown Etiology to Consider in the Differential Diagnosis of Type II Collagen Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.disorders_of_unknown_etiolo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.disorders_of_unknown_etiolo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Disorder</th></tr><tr><th headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2" id="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/type II collagen disorders</th><th headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2" id="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from type II collagen disorders</th></tr></thead><tbody><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Intermediate severity <sup>1</sup></b>
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|
</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile idiopathic arthritis</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents in childhood, usually w/joint pain</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities <sup>2</sup></td></tr><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Calve-Legg-Perthes <sup>3</sup></td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Presents in childhood, usually w/hip pain</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities; <sup>2</sup> often unilateral, & if bilateral (10%-15% of affected individuals), often asynchronous involvement (femoral heads in different stages of disease); no spine involvement</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" colspan="3" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">
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<b>Mild severity <sup>4</sup></b>
|
|
</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rheumatoid arthritis</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Joint pain; radiographic skeletal changes of osteoarthritis</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">More pronounced clinical & laboratory signs of inflammation</td></tr><tr><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Juvenile idiopathic arthritis</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Joint pain</td><td headers="hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_1_2 hd_h_collagen-2.T.disorders_of_unknown_etiolo_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No facial, ophthalmic, or auditory abnormalities; <sup>2</sup> often presents at younger age</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="collagen-2.TF.2b.1"><p class="no_margin">Intermediate severity type II collagen disorders include <i>COL2A1</i>-related spondyloperipheral dysplasia, spondyloepiphyseal dysplasia (SED) with metatarsal shortening, and Stickler syndrome. Note: Shortening of the third and/or fourth toes is a classic distinguishing hallmark of SED with metatarsal shortening.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="collagen-2.TF.2b.2"><p class="no_margin">Comprising characteristic type II collagen ocular, auditory, and orofacial abnormalities (i.e., high myopia, retinal detachment, hearing impairment, Pierre Robin sequence)</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="collagen-2.TF.2b.3"><p class="no_margin"><i>COL2A1</i> pathogenic variants have been associated with a Calve-Legg-Perthes-like phenotype (more accurately dysplastic proximal femoral epiphyses). Bilateral hip involvement, especially symmetrical and synchronous, is suggestive of a type II collagen disorder. Bilateral involvement of femoral heads (including different stages of severity) warrants further attention and workup in general.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="collagen-2.TF.2b.4"><p class="no_margin">Mild severity type II collagen disorders include <i>COL2A1</i>-related mild SED w/premature arthrosis.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcollagen2Ttypeiicollagendisorders"><div id="collagen-2.T.type_ii_collagen_disorders" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Type II Collagen Disorders: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.type_ii_collagen_disorders_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/<br />Concern</th><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_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_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeleton</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Complete radiographic survey if indicated</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Often already performed to establish diagnosis</div></li><li class="half_rhythm"><div>To assess extent of skeletal malformations</div></li></ul>
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</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cervical spine</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Flexion-extension radiograph</div></li><li class="half_rhythm"><div>Flexion-extension MRI if instability & compression seen on radiographs or interpretation on radiographs is limited (e.g., in young persons w/delayed ossification in upper cervical spine)</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for cervical instability & risk of spinal cord compression.</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Thoracolumbar spine</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical exam & radiographs where indicated</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for progressive scoliosis.</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Respiratory</b>
|
|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Pulmonary function tests</div></li><li class="half_rhythm"><div>Polysomnography</div></li></ul>
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|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess extent of respiratory insufficiency in severe presentations (PRS, small thorax, pulmonary hypoplasia)</div></li><li class="half_rhythm"><div>To identify sleep apnea (central sleep apnea as result of unrecognized unstable cervical spine, obstructive sleep apnea as result of tracheobronchomalacia & cleft palate sequelae)</div></li><li class="half_rhythm"><div>To identify respiratory insufficiency in those w/severe kyphoscoliosis</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Eyes</b>
|
|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dilated eye exam</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Preferably by expert ophthalmologist familiar w/ophthalmic complications (e.g., high myopia, vitreous changes, retinal detachment, early cataract, vision problems, blindness) in type II collagen disorders</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>ENT/Mouth</b>
|
|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hearing eval</div></li><li class="half_rhythm"><div>Eval for cleft palate</div></li></ul>
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|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding</b>
|
|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Swallowing assessment</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In persons w/PRS</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Musculoskeletal</b>
|
|
</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical exam</div></li><li class="half_rhythm"><div>Referral to orthopedic surgeon if indicated</div></li><li class="half_rhythm"><div>Referral to PT if indicated</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Functional testing / activities of daily living should be considered</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic counseling</b>
|
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_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_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of type II collagen disorders to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychosocial issues</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Awareness & referral to <a href="#collagen-2.Resources">resources</a></td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Issues related to short stature, dysmorphic facial features, poor eyesight &/or hearing impairment, pain, etc.</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">Adapted from <a class="bibr" href="#collagen-2.REF.savarirayan.2019.2070" rid="collagen-2.REF.savarirayan.2019.2070">Savarirayan et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MOI = mode of inheritance; PRS = Pierre Robin sequence; PT = physical therapist</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="collagen-2.TF.3.1"><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="figobcollagen2Ttypeiicollagendisorders1"><div id="collagen-2.T.type_ii_collagen_disorders_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Type II Collagen Disorders: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.type_ii_collagen_disorders_1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_1_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_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_1_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_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cervical spine instability w/spine compression</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical mgmt for medullopathy (C1-C2 fixation)</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt by expert familiar w/rare skeletal dysplasia & spine involvement</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Scoliosis</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgery for severe, progressive scoliosis</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In young children, progressive scoliosis can be treated non-surgically (e.g., brace).</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory insufficiency</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Supported ventilation (e.g., CPAP)</div></li><li class="half_rhythm"><div>Surgery for cleft palate</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sleep apnea</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to pulmonologist & sleep medicine physician</div></li><li class="half_rhythm"><div>Supported ventilation (e.g., CPAP)</div></li><li class="half_rhythm"><div>Surgery for PRS</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In case of central sleep apnea as result of unrecognized unstable cervical spine, referral for eval & mgmt</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cleft palate</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Surgical repair</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>High myopia, vitroretinal complications, & early cataract</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Refractive errors should be corrected w/spectacles.</div></li><li class="half_rhythm"><div>Persons at risk should be informed about signs & symptoms of retinal detachment & advised about immediate eval & treatment when symptoms occur.</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Mgmt of vitreoretinal complications by expert ophthalmologist familiar w/ophthalmic complications</div></li><li class="half_rhythm"><div>Consider prophylactic retinopexy in Stickler syndrome, <i>COL2A1</i>-related.</div></li></ul>
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</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing impairment</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing aids &/or surgery if indicated</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Joint problems (laxity, contractures, pain due to early-onset arthrosis)</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to orthopedic surgeon for eval</div></li><li class="half_rhythm"><div>Referral to PT</div></li><li class="half_rhythm"><div>Referral to OT if indicated</div></li><li class="half_rhythm"><div>Analgesics</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Advice on joint-friendly activities (e.g., swimming, cycling)</div></li><li class="half_rhythm"><div>Consider need for mobility device.</div></li><li class="half_rhythm"><div>Avoidance of physical activities that strain joints when possible</div></li></ul>
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</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Lower-limb malalignment</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Guided growth surgery</div></li><li class="half_rhythm"><div>Osteotomy</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Obesity</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to clinical nutritionist</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Even if weight is normal, importance of avoiding obesity should be emphasized.</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychosocial problems</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Referral to <a href="#collagen-2.Resources">resources</a></div></li><li class="half_rhythm"><div>Referral to psychologist</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Adapted from <a class="bibr" href="#collagen-2.REF.savarirayan.2019.2070" rid="collagen-2.REF.savarirayan.2019.2070">Savarirayan et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CPAP = continuous positive airway pressure; OT = occupational therapist; PRS = Pierre Robin sequence; PT = physical therapist</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcollagen2Ttypeiicollagendisorders2"><div id="collagen-2.T.type_ii_collagen_disorders_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Type II Collagen Disorders: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK540447/table/collagen-2.T.type_ii_collagen_disorders_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__collagen-2.T.type_ii_collagen_disorders_2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/<br />Concern</th><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_collagen-2.T.type_ii_collagen_disorders_2_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_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>General health</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical exam</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as indicated</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cervical spine</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Flexion-extension radiograph</div></li><li class="half_rhythm"><div>Flexion-extension MRI if instability & compression on radiographs or limited interpretation on radiographs</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 2-3 yrs in those w/severe type II collagen disorder & no instability</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Thoracolumbar spine</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical exam</div></li><li class="half_rhythm"><div>Radiographs when indicated</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos depending on severity</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Pulmonary function tests</div></li><li class="half_rhythm"><div>Polysomnography</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">On regular basis in persons w/severe type II collagen disorder or severe progressive kyphoscoliosis</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Eyes</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dilated eye exam</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Annually unless complications</div></li><li class="half_rhythm"><div>Consider prophylactic retinopexy in Stickler syndrome, <i>COL2A1</i>-related.</div></li></ul>
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</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>ENT/Mouth</b>
|
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hearing eval</div></li><li class="half_rhythm"><div>Eval for cleft palate & palatal insufficiency</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos depending on severity</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Feeding</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Swallowing assessment</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">On regular basis until normal feeding</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_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_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical exam</div></li><li class="half_rhythm"><div>Referral to orthopedic surgeon if indicated</div></li><li class="half_rhythm"><div>Referral to PT if indicated</div></li></ul>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_3" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as indicated</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Obesity</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Weight</td></tr><tr><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychosocial concerns</b>
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</td><td headers="hd_h_collagen-2.T.type_ii_collagen_disorders_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Specific attention to any issues when taking history & during physical exam</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">Adapted from <a class="bibr" href="#collagen-2.REF.savarirayan.2019.2070" rid="collagen-2.REF.savarirayan.2019.2070">Savarirayan et al [2019]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">PT = physical therapist</p></div></dd></dl></dl></div></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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