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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK62112_"><span class="title" itemprop="name">Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: CHST3 Deficiency, <i>CHST3</i>-Related Skeletal Dysplasia, Recessive Larsen Syndrome</div><div class="contrib half_rhythm"><span itemprop="author">Andrea Superti-Furga</span>, MD<div class="affiliation small">Professor, Division of Genetic Medicine<br />University of Lausanne;<br />Genetica AG<br />Lausanne, Switzerland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="hc.linu@itrepusa" class="oemail">hc.linu@itrepusa</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Sheila Unger</span>, MD<div class="affiliation small">Genetica AG<br />Lausanne, Switzerland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="hc.aciteneg@regnu.s" class="oemail">hc.aciteneg@regnu.s</a></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">September 1, 2011</span>; Last Update: <span itemprop="dateModified">August 1, 2024</span>.</p><p><em>Estimated reading time: 18 minutes</em></p></div><div class="body-content whole_rhythm" itemprop="text"><div id="cd-chst3.Summary" itemprop="description"><h2 id="_cd-chst3_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>) is characterized by short stature of prenatal onset, joint dislocations (knees, hips, radial heads), clubfeet, and limitation of range of motion that can involve all large joints. Kyphosis and occasionally scoliosis with slight shortening of the trunk develop in childhood. Minor heart valve dysplasia has been described in several persons. Intellect and vision are normal.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of CDCJD-<i>CHST3</i> is established in a proband with characteristic clinical and radiographic features and biallelic pathogenic variants in <i>CHST3</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Surgical correction of the abnormal joints is the only treatment modality; however, surgical correction is often only partially successful and multiple procedures are needed. Physical therapy has not been effective. Treatment of cardiac manifestations as needed per cardiologist; treatment of dental anomalies as needed per dentist.</p><p><i>Surveillance:</i> Clinical joint and spine evaluation with orthopedist with experience in skeletal dysplasia; radiographs as recommended per orthopedist; if normal at the time of diagnosis, echocardiogram should be repeated per cardiologist or every five years; follow up with dentist annually or as needed.</p><p><i>Agents/circumstances to avoid:</i> Activities with a high impact on joints (e.g., jogging) and obesity.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>CDCJD-<i>CHST3</i> is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a <i>CHST3</i> pathogenic variant, each sib of an affected individual has a 25% chance at conception of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i>CHST3</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members and prenatal/preimplantation genetic testing for a pregnancy at increased risk are possible.</p></div></div><div id="cd-chst3.Diagnosis"><h2 id="_cd-chst3_Diagnosis_">Diagnosis</h2><div id="cd-chst3.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>) <b>should be suspected</b> in individuals with the following clinical radiographic features and family history.</p><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div>Joint dislocations at birth (knees, hips, radial heads) with short stature (See <a class="figpopup" href="/books/NBK62112/figure/cd-chst3.F1/?report=objectonly" target="object" rid-figpopup="figcdchst3F1" rid-ob="figobcdchst3F1">Figure 1</a>.)</div></li><li class="half_rhythm"><div>Clubfeet</div></li><li class="half_rhythm"><div>Limitation of range of motion that can involve all large joints</div></li><li class="half_rhythm"><div>Development of kyphosis and occasionally scoliosis with slight shortening of the trunk in childhood</div></li></ul><p>
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<b>Radiographic features</b>
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</p><ul><li class="half_rhythm"><div>Progressive spondyloepiphyseal dysplasia with joint anomalies</div><ul><li class="half_rhythm"><div>Generalized mild epiphyseal dysplasia (small epiphyses)</div></li><li class="half_rhythm"><div>Delayed ossification of the capital femoral epiphyses and femoral necks</div></li><li class="half_rhythm"><div>Coxa valga (increase in the angle formed between the head and neck of the femur and the shaft of the femur)</div></li></ul></li><li class="half_rhythm"><div>Spinal abnormalities</div><ul><li class="half_rhythm"><div>Conspicuous increase in interpediculate distance from T12 to L1 or L2 (See <a class="figpopup" href="/books/NBK62112/figure/cd-chst3.F2/?report=objectonly" target="object" rid-figpopup="figcdchst3F2" rid-ob="figobcdchst3F2">Figure 2</a>.)</div></li><li class="half_rhythm"><div>Notching of the vertebral bodies, similar in appearance to coronal clefts (See <a class="figpopup" href="/books/NBK62112/figure/cd-chst3.F3/?report=objectonly" target="object" rid-figpopup="figcdchst3F3" rid-ob="figobcdchst3F3">Figure 3</a>.)</div></li></ul></li><li class="half_rhythm"><div>Normal thumbs (not spatulate)</div></li><li class="half_rhythm"><div>Normal or (more rarely) slightly advanced bone age (especially carpal)</div></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="cd-chst3.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of CDCJD-<i>CHST3</i>
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<b>is established</b> in a proband with <a href="#cd-chst3.Suggestive_Findings">suggestive findings</a> and biallelic pathogenic (or likely pathogenic) variants in <i>CHST3</i> identified by molecular genetic testing (see <a href="/books/NBK62112/table/cd-chst3.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobcdchst3Tmoleculargenetictestinguse">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [<a class="bk_pop" href="#cd-chst3.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this <i>GeneReview</i> is understood to include likely pathogenic variants. (2) Identification of biallelic <i>CHST3</i> variants of uncertain significance (or of one known <i>CHST3</i> pathogenic variant and one <i>CHST3</i> variant of uncertain significance) does not establish or rule out the diagnosis.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see <a href="#cd-chst3.Option_1">Option 1</a>), whereas comprehensive genomic testing does not (see <a href="#cd-chst3.Option_2">Option 2</a>).</p><div id="cd-chst3.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>CHST3</i> is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</p><p><b>A skeletal dysplasia or skeletal dysplasia with multiple dislocations multigene panel</b> that includes <i>CHST3</i> and other genes of interest (see <a href="#cd-chst3.Differential_Diagnosis">Differential Diagnosis</a>) may be considered to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="cd-chst3.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. To date, the majority of <i>CHST3</i> pathogenic variants reported (e.g., missense, nonsense) are within the coding region and are likely to be identified on exome sequencing.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="cd-chst3.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Identified by Method</th></tr></thead><tbody><tr><td headers="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHST3</i>
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</td><td headers="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99%</td></tr><tr><td headers="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></td><td headers="hd_h_cd-chst3.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1 reported <sup>5</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="cd-chst3.TF.1.1"><p class="no_margin">See <a href="/books/n/gene/spg17/#spg17.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd><dt>2. </dt><dd><div id="cd-chst3.TF.1.2"><p class="no_margin">See <a href="#cd-chst3.Molecular_Genetics">Molecular Genetics</a> for information on variants in this gene.</p></div></dd><dt>3. </dt><dd><div id="cd-chst3.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="cd-chst3.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.</p></div></dd><dt>5. </dt><dd><div id="cd-chst3.TF.1.5"><p class="no_margin">
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<a class="bk_pop" href="#cd-chst3.REF.ranza.2017.868">Ranza et al [2017]</a>
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</p></div></dd></dl></div></div></div></div><div id="cd-chst3.Biochemical_Testing"><h4>Biochemical Testing</h4><p>Cultured fibroblasts can be used to determine proteoglycan sulfation (i.e., sulfotransferase activity). The fibroblasts are incubated with radioactive sulfate [<sup>35</sup>S] and chondroitin. In all individuals with CHST3 deficiency studied thus far, the incorporation of sulfate at the C6 position was dramatically decreased while incorporation at the C4 position was within normal levels [<a class="bk_pop" href="#cd-chst3.REF.hermanns.2008.1368">Hermanns et al 2008</a>, <a class="bk_pop" href="#cd-chst3.REF.van_roij.2008.2376">van Roij et al 2008</a>]. This test requires a skin biopsy and a specialist laboratory and thus is more invasive and less widely available than molecular genetic testing. Biochemical testing can be useful in those individuals in which pathogenic variants are not identified or variants of uncertain significance have been detected. The diminished sulfation at carbon 6 of proteoglycans offers unambiguous evidence of CHST3 deficiency.</p></div></div></div><div id="cd-chst3.Clinical_Characteristics"><h2 id="_cd-chst3_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cd-chst3.Clinical_Description"><h3>Clinical Description</h3><p>Most children with chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>) are identified at birth as having a generalized skeletal disorder. The features of this disorder are generally limited to the skeleton and joints and are progressive in nature.</p><p>Occasionally, short stature and knee dislocations are seen on prenatal ultrasound examination [<a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>]. The prenatal presentation may be that of arthrogryposis [<a class="bk_pop" href="#cd-chst3.REF.muys.2017.440">Muys et al 2017</a>].</p><p>At birth, affected infants are noted to have short stature (birth length: 39-44 cm) and joint dislocations; the large majority have bilateral knee luxation or subluxation. The radial heads and hips are the next most commonly affected joints. Clubfeet are also frequently seen. Despite the congenital joint dislocations, the overall phenotype is one of restricted movement, and many children undergo multiple corrective procedures with only limited success [<a class="bk_pop" href="#cd-chst3.REF.rajab.2004.413">Rajab et al 2004</a>, <a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>, <a class="bk_pop" href="#cd-chst3.REF.searle.2014.12">Searle et al 2014</a>].</p><p>In a large family reported from Oman, the adult heights ranged from 110 cm to 130 cm [<a class="bk_pop" href="#cd-chst3.REF.rajab.2004.413">Rajab et al 2004</a>], while in a large Pakistani family the mean adult height was 84 cm [<a class="bk_pop" href="#cd-chst3.REF.waryah.2016.90">Waryah et al 2016</a>]. A review article included information on three adults with heights of 117 cm, 121 cm, and 134.5 cm [<a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>]. Adult height appears to be severely affected in all individuals with CDCJD-<i>CHST3</i>, but with some intrafamilial variability and large interfamilial variability.</p><p>Many adults develop arthritic-type changes. They also develop spinal kyphosis, frequently in the cervical spine, and (rarely) scoliosis.</p><p><b>Cardiac manifestations.</b> Minor heart valve dysplasia with valvular insufficiency has been described in multiple reports, including one in the kindred from Oman [<a class="bk_pop" href="#cd-chst3.REF.hall.1997.11">Hall 1997</a>, <a class="bk_pop" href="#cd-chst3.REF.rajab.2004.413">Rajab et al 2004</a>, <a class="bk_pop" href="#cd-chst3.REF.tuysuz.2009.375">Tuysuz et al 2009</a>, <a class="bk_pop" href="#cd-chst3.REF.otaify.2023.2100">Otaify et al 2023</a>, <a class="bk_pop" href="#cd-chst3.REF.singh.2024.e63422">Singh et al 2024</a>]. There are occasional reports of structural cardiac malformations such as atrial septal defect, but it is not yet clear if <i>CHST3</i> pathogenic variants are causally linked [<a class="bk_pop" href="#cd-chst3.REF.otaify.2023.2100">Otaify et al 2023</a>].</p><p><b>Tooth anomalies</b> (microdontia, delayed eruption) have been reported in the large Omani kindred as well as several individuals from Egypt [<a class="bk_pop" href="#cd-chst3.REF.rajab.2004.413">Rajab et al 2004</a>, <a class="bk_pop" href="#cd-chst3.REF.otaify.2023.2100">Otaify et al 2023</a>].</p><p><b>Intellect, vision, and hearing</b> is usually normal [<a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>, <a class="bk_pop" href="#cd-chst3.REF.singh.2024.e63422">Singh et al 2024</a>]. However, in a large Pakistani kindred, at least six affected individuals also had mixed hearing loss; thus, this may be an associated feature [<a class="bk_pop" href="#cd-chst3.REF.waryah.2016.90">Waryah et al 2016</a>]. One additional individual of Pakistani origin was reported to have mild bilateral hearing loss on audiometry but no clinical signs of hearing impairment [<a class="bk_pop" href="#cd-chst3.REF.kausar.2022.818">Kausar et al 2022</a>].</p><p><b>Other.</b> Sagittal craniosynostosis has been reported in a single individual [<a class="bk_pop" href="#cd-chst3.REF.searle.2014.12">Searle et al 2014</a>], while "sclerosis of sutures" was reported in three unrelated individuals [<a class="bk_pop" href="#cd-chst3.REF.srivastava.2017.163">Srivastava et al 2017</a>].</p></div><div id="cd-chst3.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations have been observed. The phenotype reported thus far has been strikingly homogeneous regardless of type of <i>CHST3</i> pathogenic variant [<a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>]. Persons with homozygous pathogenic missense variants are no less severely affected than those with nonsense variants.</p></div><div id="cd-chst3.Nomenclature"><h3>Nomenclature</h3><p>In 1950, Dr LJ Larsen described autosomal dominant Larsen syndrome, now known to be caused by pathogenic variants in <i>FLNB</i>. Larsen syndrome is characterized by multiple joint dislocations, dysmorphic facial features, spatulate thumbs, and accelerated carpal ossification (see <a href="/books/n/gene/flnb-dis/"><i>FLNB</i>-Related Disorders</a>). Following the delineation of autosomal dominant Larsen syndrome, several reports of "autosomal recessive Larsen syndrome" and other similar disorders were published. By careful reevaluation of affected individuals and through recruitment of individuals with autosomal recessive Larsen syndrome, several investigators showed that, in fact, all the various reports of autosomal recessive Larsen syndrome, humerospinal dysostosis, and spondyloepiphyseal dysplasia (SED), Omani type could be attributed to CHST3 deficiency and that the different names had arisen from the part of the phenotype the various authors had emphasized [<a class="bk_pop" href="#cd-chst3.REF.hermanns.2008.1368">Hermanns et al 2008</a>, <a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>]; that is, they were describing the same condition from different viewpoints.</p><ul><li class="half_rhythm"><div>Humerospinal dysostosis was described by <a class="bk_pop" href="#cd-chst3.REF.kozlowski.1974.407">Kozlowski et al [1974]</a> in two brothers with joint dislocations and radiographic abnormalities (bifid humeri and coronal clefts). Because the brothers were reported to be half-sibs, autosomal dominant inheritance was suspected and no link was made to autosomal recessive Larsen syndrome.</div></li><li class="half_rhythm"><div><a class="bk_pop" href="#cd-chst3.REF.m_garban_.2004.107">Mégarbané and Ghanem [2004]</a> described "a newly recognized chondrodysplasia with joint dislocations." Although they made the link to humerospinal dysostosis, they rejected that diagnosis because the evidence strongly suggested autosomal recessive inheritance.</div></li><li class="half_rhythm"><div><a class="bk_pop" href="#cd-chst3.REF.rajab.2004.413">Rajab et al [2004]</a> described a large family originating from Oman with what they termed "a new recessive type of SED with progressive spinal involvement." The same group went on to demonstrate that the disorder was caused by CHST3 deficiency and renamed the disorder SED, Omani type [<a class="bk_pop" href="#cd-chst3.REF.thiele.2004.10155">Thiele et al 2004</a>].</div></li></ul><p>The name "chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>)" has been proposed as an unbiased and inclusive designation for this disorder and is the current designation used in the Nosology of Genetic Skeletal Disorders [<a class="bk_pop" href="#cd-chst3.REF.unger.2023.1164">Unger et al 2023</a>]. However, an argument could also be made for retaining the name "autosomal recessive Larsen syndrome," as the joint dislocations are the presenting feature and "Larsen syndrome" is usually the first diagnosis considered; thus, the continued use of this designation is open to debate. The term "recessive Larsen syndrome" is more appropriate for CDCJD-<i>CHST3</i> than for the <i>B4GALT7</i>-associated linkeropathy, as bilateral knee dislocation at birth is much more common in CHST3 deficiency than in B4GALT7 deficiency.</p></div><div id="cd-chst3.Prevalence"><h3>Prevalence</h3><p>No firm data regarding the prevalence of CDCJD-<i>CHST3</i> are available. More than 100 probands (including familial recurrences) have been reported, with many of these individuals from consanguineous families.</p></div></div><div id="cd-chst3.Genetically_Related_Allelic_Dis"><h2 id="_cd-chst3_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CHST3</i>.</p></div><div id="cd-chst3.Differential_Diagnosis"><h2 id="_cd-chst3_Differential_Diagnosis_">Differential Diagnosis</h2><p>A summary of key differentiating clinical and radiographic features for chondrodysplasias with multiple dislocations is available in <a class="bk_pop" href="#cd-chst3.REF.ranza.2017.868">Ranza et al [2017]</a>. Selected genes of interest in the differential diagnosis are listed in <a href="/books/NBK62112/table/cd-chst3.T.genes_of_interest_in_the_diff/?report=objectonly" target="object" rid-ob="figobcdchst3Tgenesofinterestinthediff">Table 2</a>.</p><div id="cd-chst3.T.genes_of_interest_in_the_diff" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.genes_of_interest_in_the_diff/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.genes_of_interest_in_the_diff_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" style="text-align:left;vertical-align:middle;">Disorder <sup>1</sup></th><th id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Features of Disorder</th></tr><tr><th headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4" id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/<br />CDCJD-<i>CHST3</i></th><th headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4" id="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from<br />CDCJD-<i>CHST3</i></th></tr></thead><tbody><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B3GALT6</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SEMD w/joint laxity (Beighton type), <i>B3GALT6</i>‐related (Ehlers‐Danlos syndrome, spondylodysplastic type 2) (OMIM <a href="https://omim.org/entry/271640" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">271640</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal-onset short stature</div></li><li class="half_rhythm"><div>Joint dislocations</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Advanced bone age</div></li><li class="half_rhythm"><div>Lacks characteristic CDCJD-<i>CHST3</i> spine findings</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B4GALT7</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ehlers‐Danlos syndrome, spondylodysplastic type 1, <i>B4GALT7</i>‐related (OMIM <a href="https://omim.org/entry/130070" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">130070</a>) <sup>2</sup></td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>B3GAT3</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Multiple joint dislocations, <i>B3GAT3</i>-related (OMIM <a href="https://omim.org/entry/245600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">245600</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Osteoporosis & fractures in some</div></li><li class="half_rhythm"><div>Distinctive facial features w/protuberant eyes</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CANT1</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Desbuquois dysplasia (w/accessory ossification center in digit 2), <i>CANT1</i>‐related (OMIM <a href="https://omim.org/entry/251450" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">251450</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal-onset short stature</div></li><li class="half_rhythm"><div>Joint dislocations</div></li><li class="half_rhythm"><div>Multiple coronal clefts on lateral spine radiograph</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Distinctive facial features (marked midface hypoplasia, prominent eyes)</div></li><li class="half_rhythm"><div>Advanced bone age</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CSGALNACT1</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skeletal dysplasia w/joint laxity & advanced bone age, <i>CSGALNACT1</i>-related (OMIM <a href="https://omim.org/entry/618870" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618870</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal-onset short stature</div></li><li class="half_rhythm"><div>Joint laxity</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Joint laxity is prominent but persons may not have dislocations.</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>EXOC6B</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/exoc6b-semd/">SEMD w/joint laxity, <i>EXOC6B</i>-related</a>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Multiple joint dislocations</div></li><li class="half_rhythm"><div>Scoliosis & kyphosis</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Normal birth length</div></li><li class="half_rhythm"><div>Very delayed proximal carpal ossification</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>FLNB</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Larsen syndrome, <i>FLNB</i>-related (See <a href="/books/n/gene/flnb-dis/"><i>FLNB</i>-Related Disorders</a>.)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Multiple dislocations</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Normal birth length</div></li><li class="half_rhythm"><div>Distinctive facial features w/↑ incidence of cleft palate</div></li><li class="half_rhythm"><div>Advanced bone age</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>KIF22</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">SEMD w/joint laxity (Hall type or leptodactylic type), <i>KIF22</i>-related (OMIM <a href="https://omim.org/entry/603546" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">603546</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">Distinctive facial features</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SLC10A7</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skeletal dysplasia w/joint dislocations & amelogenesis imperfecta, <i>SLC10A7</i>‐related (OMIM <a href="https://omim.org/entry/618363" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618363</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal-onset short stature</div></li><li class="half_rhythm"><div>Multiple dislocations</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Amelogenesis</div></li><li class="half_rhythm"><div>Advanced carpal ossification</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SLC26A2</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/diastrophic-d/">Diastrophic dysplasia, <i>SLC26A2</i>‐related</a>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Short limbs</div></li><li class="half_rhythm"><div>Clubfeet</div></li><li class="half_rhythm"><div>Joint stiffness / limited mobility</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hitchhiker thumb</div></li><li class="half_rhythm"><div>Lacks characteristic CDCJD-<i>CHST3</i> spine findings</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>XYLT1</i>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Baratela‐Scott syndrome, <i>XYLT1</i>‐related (OMIM <a href="https://omim.org/entry/615777" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">615777</a>)</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Prenatal-onset short stature</div></li><li class="half_rhythm"><div>Joint dislocations</div></li><li class="half_rhythm"><div>Multiple coronal clefts on lateral spine radiograph</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_1_4 hd_h_cd-chst3.T.genes_of_interest_in_the_diff_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Distinctive facial features (marked midface hypoplasia, prominent eyes)</div></li><li class="half_rhythm"><div>Advanced bone age</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SEMD = spondyloepimetaphyseal dysplasia</p></div></dd><dt>1. </dt><dd><div id="cd-chst3.TF.2.1"><p class="no_margin">Disorder terminology is based on the 2023 revision of the Nosology of Genetic Skeletal Disorders [<a class="bk_pop" href="#cd-chst3.REF.unger.2023.1164">Unger et al 2023</a>].</p></div></dd><dt>2. </dt><dd><div id="cd-chst3.TF.2.2"><p class="no_margin">The La Réunion variant of recessive Larsen syndrome is caused by a specific <i>B4GALT7</i> pathogenic variant [<a class="bk_pop" href="#cd-chst3.REF.cartault.2015.49">Cartault et al 2015</a>].</p></div></dd></dl></div></div></div></div><div id="cd-chst3.Management"><h2 id="_cd-chst3_Management_">Management</h2><p>No clinical practice guidelines for chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.</p><div id="cd-chst3.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease in an individual diagnosed with CDCJD-<i>CHST3</i>, the evaluations summarized in <a href="/books/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni/?report=objectonly" target="object" rid-ob="figobcdchst3Tchondrodysplasiawithcongeni">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="cd-chst3.T.chondrodysplasia_with_congeni" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related: Recommended Evaluations Following Initial Diagnosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.chondrodysplasia_with_congeni_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_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_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Orthopedic referral</div></li><li class="half_rhythm"><div>Referral to specialized skeletal dysplasia clinic if available</div></li><li class="half_rhythm"><div>Radiographs per orthopedist</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic counseling</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_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_cd-chst3.T.chondrodysplasia_with_congeni_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 CDCJD-<i>CHST3</i> to facilitate medical & personal decision making</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">MOI = mode of inheritance</p></div></dd><dt>1. </dt><dd><div id="cd-chst3.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="cd-chst3.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/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni_1/?report=objectonly" target="object" rid-ob="figobcdchst3Tchondrodysplasiawithcongeni1">Table 4</a>).</p><div id="cd-chst3.T.chondrodysplasia_with_congeni_1" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related: Treatment of Manifestations</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni_1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.chondrodysplasia_with_congeni_1_lrgtbl__"><table><thead><tr><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_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_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment for joint & spine manifestations per orthopedist w/experience in skeletal dysplasia</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Surgical correction is often only partially successful for joint dislocations & most persons have had multiple procedures by adulthood [<a class="bk_pop" href="#cd-chst3.REF.unger.2010.2543">Unger et al 2010</a>].</div></li><li class="half_rhythm"><div>Physical therapy has not been demonstrated to be effective in this disorder.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of cardiac disease per cardiologist & cardiothoracic surgeon</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of dental manifestations per dentist & orthodontist</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></div><div id="cd-chst3.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/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni_2/?report=objectonly" target="object" rid-ob="figobcdchst3Tchondrodysplasiawithcongeni2">Table 5</a> are recommended.</p><div id="cd-chst3.T.chondrodysplasia_with_congeni_2" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Chondrodysplasia with Congenital Joint Dislocations, <i>CHST3</i>-Related: Recommended Surveillance</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.chondrodysplasia_with_congeni_2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.chondrodysplasia_with_congeni_2_lrgtbl__"><table><thead><tr><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_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_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Skeletal</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Clinical joint & spine eval w/orthopedist w/experience in skeletal dysplasia</div></li><li class="half_rhythm"><div>Radiographs as recommended by orthopedist</div></li></ul>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Individualized depending on progression or stability of findings</td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Follow-up echocardiogram</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency per cardiologist or approximately every 5 yrs</td></tr><tr><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental</b>
|
||
</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Follow-up eval w/dentist</td><td headers="hd_h_cd-chst3.T.chondrodysplasia_with_congeni_2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as needed</td></tr></tbody></table></div></div></div><div id="cd-chst3.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Activities with a high impact on joints (e.g., jogging) should be avoided.</p><p>Obesity, which places an excessive load on the large weight-bearing joints, should be avoided.</p></div><div id="cd-chst3.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#cd-chst3.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="cd-chst3.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 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="cd-chst3.Genetic_Counseling"><h2 id="_cd-chst3_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="cd-chst3.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related (CDCJD-<i>CHST3</i>) is inherited in an autosomal recessive manner.</p></div><div id="cd-chst3.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a proband</b>
|
||
</p><ul><li class="half_rhythm"><div>The parents of an affected child are presumed to be heterozygous for a <i>CHST3</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm that both parents are heterozygous for a <i>CHST3</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="bk_pop" href="#cd-chst3.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>Heterozygotes (carriers) are asymptomatic. There is no evidence that they are at increased risk for degenerative joint disease.</div></li></ul><p>
|
||
<b>Sibs of a proband</b>
|
||
</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>CHST3</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing CDCJD-<i>CHST3</i>.</div></li></ul><p><b>Offspring of a proband.</b> Unless an affected individual's reproductive partner also has CDCJD-<i>CHST3</i> or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>CHST3</i>.</p><p><b>Other family members.</b> Each sib of the proband's parents is at 50% risk of being a carrier of a <i>CHST3</i> pathogenic variant.</p></div><div id="cd-chst3.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>CHST3</i> pathogenic variants in the family.</p></div><div id="cd-chst3.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><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, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing should be considered for the reproductive partners of known carriers and for the reproductive partners of individuals affected with CDCJD-<i>CHST3</i>, particularly if consanguinity is likely and/or both partners are of the same ancestry. A founder variant has been identified in the Amish community (see <a href="/books/NBK62112/table/cd-chst3.T.chst3_pathogenic_variants_ref/?report=objectonly" target="object" rid-ob="figobcdchst3Tchst3pathogenicvariantsref">Table 6</a>).</div></li></ul></div><div id="cd-chst3.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>CHST3</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing for CDCJD-<i>CHST3</i> is 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 centers 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="cd-chst3.Resources"><h2 id="_cd-chst3_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/">here</a>.</i></p>
|
||
<ul><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="cd-chst3.Molecular_Genetics"><h2 id="_cd-chst3_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="cd-chst3.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Chondrodysplasia with Congenital Joint Dislocations, CHST3-Related: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cd-chst3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cd-chst3.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cd-chst3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cd-chst3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cd-chst3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cd-chst3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/9469" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>CHST3</i>
|
||
</a>
|
||
</td><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=9469" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">10q22<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q7LGC8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Carbohydrate sulfotransferase 3</a>
|
||
</td><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.LOVD.nl/CHST3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHST3 @ LOVD</a>
|
||
</td><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CHST3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHST3</a>
|
||
</td><td headers="hd_b_cd-chst3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CHST3[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHST3</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="cd-chst3.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
chromosome locus from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="cd-chst3.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Chondrodysplasia with Congenital Joint Dislocations, CHST3-Related (<a href="/omim/143095,603799" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/143095" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">143095</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPONDYLOEPIPHYSEAL DYSPLASIA WITH CONGENITAL JOINT DISLOCATIONS; SEDCJD</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/603799" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603799</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CARBOHYDRATE SULFOTRANSFERASE 3; CHST3</td></tr></tbody></table></div></div><div id="cd-chst3.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CHST3</i> encodes carbohydrate sulfotransferase 3, the enzyme responsible for the transfer of sulfate from PAPS to position 6 of N-acetyl galactosamine. Proper sulfation of the chondroitin sulfate proteoglycans is essential for normal cartilage structure.</p><p>Sulfation studies as well as the nature of the known pathogenic variants and the mode of inheritance suggest that the pathogenesis of the disorder results from decreased/absent catalytic activity of the enzyme. No hot spots have been identified, but the majority of known pathogenic variants are clustered in the sulfotransferase domain.</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div id="cd-chst3.T.chst3_pathogenic_variants_ref" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>CHST3</i> Pathogenic Variants Referenced in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK62112/table/cd-chst3.T.chst3_pathogenic_variants_ref/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cd-chst3.T.chst3_pathogenic_variants_ref_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004273.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004273<wbr style="display:inline-block"></wbr>.5</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_004264.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004264<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1298C>T</td><td headers="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro433Leu</td><td headers="hd_h_cd-chst3.T.chst3_pathogenic_variants_ref_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Amish community [<a class="bk_pop" href="#cd-chst3.REF.puffenberger.2021.3322">Puffenberger 2021</a>]</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="cd-chst3.Chapter_Notes"><h2 id="_cd-chst3_Chapter_Notes_">Chapter Notes</h2><div id="cd-chst3.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>1 August 2024 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>31 January 2019 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>1 September 2011 (me) Review posted live</div></li><li class="half_rhythm"><div>28 March 2011 (asf) Original submission</div></li></ul></div></div><div id="cd-chst3.References"><h2 id="_cd-chst3_References_">References</h2><div id="cd-chst3.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.cartault.2015.49">Cartault
|
||
F, Munier
|
||
P, Jacquemont
|
||
M-L, Vellayoudom
|
||
J, Doray
|
||
B, Payet
|
||
C, Randrianaivo
|
||
H, Laville
|
||
J-M, Munnich
|
||
A, Cormier-Daire
|
||
V. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome.
|
||
Eur J Hum Genet.
|
||
2015;23:49–53.
|
||
[<a href="/pmc/articles/PMC4266744/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4266744</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24755949" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24755949</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.hall.1997.11">Hall
|
||
BD. Humero-spinal dysostosis: report of the fourth case with emphasis on generalized skeletal involvement, abnormal craniofacial features, and mitral valve thickening.
|
||
J Pediatr Orthop B.
|
||
1997;6:11–4.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/9039660" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9039660</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.hermanns.2008.1368">Hermanns
|
||
P, Unger
|
||
S, Rossi
|
||
A, Perez-Aytes
|
||
A, Cortina
|
||
H, Bonafé
|
||
L, Boccone
|
||
L, Setzu
|
||
V, Dutoit
|
||
M, Sangiorgi
|
||
L, Pecora
|
||
F, Reicherter
|
||
K, Nishimura
|
||
G, Spranger
|
||
J, Zabel
|
||
B, Superti-Furga
|
||
A. Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis.
|
||
Am J Hum Genet.
|
||
2008;82:1368–74.
|
||
[<a href="/pmc/articles/PMC2427316/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2427316</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18513679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18513679</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.j_nsson.2017.519">Jónsson
|
||
H, Sulem
|
||
P, Kehr
|
||
B, Kristmundsdottir
|
||
S, Zink
|
||
F, Hjartarson
|
||
E, Hardarson
|
||
MT, Hjorleifsson
|
||
KE, Eggertsson
|
||
HP, Gudjonsson
|
||
SA, Ward
|
||
LD, Arnadottir
|
||
GA, Helgason
|
||
EA, Helgason
|
||
H, Gylfason
|
||
A, Jonasdottir
|
||
A, Jonasdottir
|
||
A, Rafnar
|
||
T, Frigge
|
||
M, Stacey
|
||
SN, Th Magnusson
|
||
O, Thorsteinsdottir
|
||
U, Masson
|
||
G, Kong
|
||
A, Halldorsson
|
||
BV, Helgason
|
||
A, Gudbjartsson
|
||
DF, Stefansson
|
||
K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland.
|
||
Nature.
|
||
2017;549:519-22.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.kausar.2022.818">Kausar
|
||
M, Ain
|
||
NU, Hayat
|
||
F, Fatima
|
||
H, Azim
|
||
S, Ullah
|
||
H, Mushtaq
|
||
M, Khalid
|
||
S, Hussain
|
||
S, Naz
|
||
S, Janjua
|
||
J, Amjad
|
||
SB, Baig
|
||
RM, Makitie
|
||
O, Qamar
|
||
R, Ikegawa
|
||
S, Gen
|
||
N, Khor
|
||
CC, Foo
|
||
JN, Siddiqi
|
||
S. Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.
|
||
BMC Musculoskelet Disord.
|
||
2022;23:818.
|
||
[<a href="/pmc/articles/PMC9426025/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9426025</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36042462" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36042462</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.kozlowski.1974.407">Kozlowski
|
||
KS, Celermajer
|
||
JM, Tink
|
||
AR. Humero-spinal dysostosis with congenital heart disease.
|
||
Am J Dis Child.
|
||
1974;127:407–10.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/4814886" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4814886</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.m_garban_.2004.107">Mégarbané
|
||
A, Ghanem
|
||
I.
|
||
A newly recognized chondrodysplasia with multiple dislocations.
|
||
Am J Med Genet A.
|
||
2004;130A:107–9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15368507" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15368507</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.muys.2017.440">Muys
|
||
J, Blaumeiser
|
||
B, Jacquemyn
|
||
Y, Janssens
|
||
K. Prenatal homozygosity mapping detects a novel mutation in CHST3 in a fetus with skeletal dysplasia and joint dislocations.
|
||
Clin Case Rep.
|
||
2017;5:440–5.
|
||
[<a href="/pmc/articles/PMC5378824/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5378824</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28396765" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28396765</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.otaify.2023.2100">Otaify
|
||
GA, Elhossini
|
||
RM, Abdel-Ghafar
|
||
SF, Sayed
|
||
IM, Abdel-Salam
|
||
GMH, Aglan
|
||
MS, Abdel-Hamid
|
||
MS. CHST3-related skeletal dysplasia in 14 patients: identification of 8 novel variants and further expansion of the phenotypic spectrum. : Am J Med Genet A.
|
||
2023;191:2100-12.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/37183573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37183573</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.puffenberger.2021.3322">Puffenberger
|
||
EG. Mendelian disease research in the Plain populations of Lancaster County, Pennsylvania.
|
||
Am J Med Genet A.
|
||
2021;185:3322-33.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/34532947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34532947</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.rajab.2004.413">Rajab
|
||
A, Kunze
|
||
J, Mundlos
|
||
S.
|
||
Spondyloepiphyseal dysplasia Omani type: a new recessive type of SED with progressive spinal involvement.
|
||
Am J Med Genet A.
|
||
2004;126A:413–9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/15098240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15098240</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.ranza.2017.868">Ranza
|
||
E, Huber
|
||
C, Levin
|
||
N, Baujat
|
||
G, Boyle-Feysot
|
||
C, Nitschke
|
||
P, Masson
|
||
C, Alanay
|
||
Y, Al-Gazali
|
||
L, Bitoun
|
||
P, Boute
|
||
O, Campeau
|
||
P, Coubes
|
||
C, McEntagart
|
||
M, Elcioglu
|
||
N, Faivre
|
||
L, Gezdirici
|
||
A, Johnson
|
||
D, Mihci
|
||
E, Nur
|
||
BG, Perrin
|
||
L, Quelin
|
||
C, Terhal
|
||
P, Tuysuz
|
||
B, Cormier-Daire
|
||
V. Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.
|
||
Clin Genet.
|
||
2017;91:868–80.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/28229453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28229453</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.richards.2015.405">Richards
|
||
S, Aziz
|
||
N, Bale
|
||
S, Bick
|
||
D, Das
|
||
S, Gastier-Foster
|
||
J, Grody
|
||
WW, Hegde
|
||
M, Lyon
|
||
E, Spector
|
||
E, Voelkerding
|
||
K, Rehm
|
||
HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
|
||
Genet Med.
|
||
2015;17:405-24.
|
||
[<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.searle.2014.12">Searle
|
||
C, Jewell
|
||
R, Kraft
|
||
J, Stoebe
|
||
P, Chumas
|
||
P, Titheradge
|
||
H, Kraus
|
||
A, Gencik
|
||
M, Hobson
|
||
E.
|
||
Craniosynostosis: a previously unreported association with CHST3-related skeletal dysplasia (autosomal recessive Larsen syndrome).
|
||
Clin Dysmorphol.
|
||
2014;23:12–5.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24300290" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24300290</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.singh.2024.e63422">Singh
|
||
S, Jacob
|
||
P, Patil
|
||
SJ, Muranjan
|
||
M, Shah
|
||
H, Girisha
|
||
KM, Bhavani
|
||
GS. Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations: Am J Med Genet A.
|
||
2024; 194:e63422
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/37876363" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 37876363</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.srivastava.2017.163">Srivastava
|
||
P, Pandey
|
||
H, Agarwal
|
||
D, Mandal
|
||
K, Phadke
|
||
SR. Spondyloepiphyseal dysplasia Omani type: CHST3 mutation spectrum and phenotypes in three Indian families.
|
||
Am J Med Genet A.
|
||
2017;173:163–8.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/27753269" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27753269</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.thiele.2004.10155">Thiele
|
||
H, Sakano
|
||
M, Kitagawa
|
||
H, Sugahara
|
||
K, Rajab
|
||
A, Höhne
|
||
W, Ritter
|
||
H, Leschik
|
||
G, Nürnberg
|
||
P, Mundlos
|
||
S.
|
||
Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement.
|
||
Proc Natl Acad Sci U S A.
|
||
2004;101:10155–60.
|
||
[<a href="/pmc/articles/PMC454181/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC454181</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15215498" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15215498</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.tuysuz.2009.375">Tuysuz
|
||
B, Mizumoto
|
||
S, Sugahara
|
||
K, Celebi
|
||
A, Mundlos
|
||
S, Turkmen
|
||
S. Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3.
|
||
Clin Genet.
|
||
2009;75:375–83.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/19320654" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19320654</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.unger.2023.1164">Unger
|
||
S, Ferreira
|
||
CR, Mortier
|
||
GR, Ali
|
||
H, Bertola
|
||
DR, Calder
|
||
A, Cohn
|
||
DH, Cormier-Daire
|
||
V, Girisha
|
||
KM, Hall
|
||
C, Krakow
|
||
D, Makitie
|
||
O, Mundlos
|
||
S, Nishimura
|
||
G, Robertson
|
||
SP, Savarirayan
|
||
R, Sillence
|
||
D, Simon
|
||
M, Sutton
|
||
VR, Warman
|
||
ML, Superti-Furga
|
||
A. Nosology of genetic skeletal disorders: 2023 revision.
|
||
Am J Med Genet A.
|
||
2023;191:1164-209.
|
||
[<a href="/pmc/articles/PMC10081954/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10081954</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36779427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36779427</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.unger.2010.2543">Unger
|
||
S, Lausch
|
||
E, Rossi
|
||
A, Mégarbané
|
||
A, Sillence
|
||
D, Alcausin
|
||
M, Aytes
|
||
A, Mendoza-Londono
|
||
R, Nampoothiri
|
||
S, Afroze
|
||
B, Hall
|
||
B, Lo
|
||
IF, Lam
|
||
ST, Hoefele
|
||
J, Rost
|
||
I, Wakeling
|
||
E, Mangold
|
||
E, Godbole
|
||
K, Vatanavicharn
|
||
N, Franco
|
||
LM, Chandler
|
||
K, Hollander
|
||
S, Velten
|
||
T, Reicherter
|
||
K, Spranger
|
||
J, Robertson
|
||
S, Bonafé
|
||
L, Zabel
|
||
B, Superti-Furga
|
||
A. Phenotypic features of carbohydrate sulfotransferase 3 (CHST3) deficiency in 24 patients: congenital dislocations and vertebral changes as principal diagnostic features.
|
||
Am J Med Genet A.
|
||
2010;152A:2543–9.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/20830804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20830804</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.van_roij.2008.2376">van Roij
|
||
MH, Mizumoto
|
||
S, Yamada
|
||
S, Morgan
|
||
T, Tan-Sindhunata
|
||
MB, Meijers-Heijboer
|
||
H, Verbeke
|
||
JI, Markie
|
||
D, Sugahara
|
||
K, Robertson
|
||
SP. Spondyloepiphyseal dysplasia, Omani type: further definition of the phenotype.
|
||
Am J Med Genet A.
|
||
2008;146A:2376–84.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/18698629" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18698629</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="cd-chst3.REF.waryah.2016.90">Waryah
|
||
AM, Shahzad
|
||
M, Shaikh
|
||
H, Sheikh
|
||
SA, Channa
|
||
NA, Hufnagel
|
||
RB, Makhdoom
|
||
A, Riazuddin
|
||
S, Ahmed
|
||
ZM. A novel CHST3 allele associated with spondyloepiphyseal dysplasia and hearing loss in Pakistani kindred.
|
||
Clin Genet.
|
||
2016;90:90–5.
|
||
[<a href="/pmc/articles/PMC4870159/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4870159</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26572954" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26572954</span></a>]</div></li></ul></div></div><div class="bk_prnt_sctn"><h2>Figures</h2><div class="whole_rhythm bk_prnt_obj bk_first_prnt_obj"><div id="cd-chst3.F1" class="figure bk_fig"><div class="graphic"><img src="/books/NBK62112/bin/cd-chst3-Image001.jpg" alt="Figure 1. . A newborn with chondrodysplasia with congenital joint dislocations, CHST3-related." /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>A newborn with chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related. Note the bilateral dislocation of the knees and radial heads.</p></div></div></div><div class="whole_rhythm bk_prnt_obj"><div id="cd-chst3.F2" class="figure bk_fig"><div class="graphic"><img src="/books/NBK62112/bin/cd-chst3-Image002.jpg" alt="Figure 2. . An individual with chondrodysplasia with congenital joint dislocations, CHST3-related." /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>An individual with chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related. Note the conspicuous increase in interpediculate distance from T12 to L1. Also appreciable is the bilateral hip subluxation.</p></div></div></div><div class="whole_rhythm bk_prnt_obj"><div id="cd-chst3.F3" class="figure bk_fig"><div class="graphic"><img src="/books/NBK62112/bin/cd-chst3-Image003.jpg" alt="Figure 3. . An individual with chondrodysplasia with congenital joint dislocations, CHST3-related." /></div><h3><span class="label">Figure 3. </span></h3><div class="caption"><p>An individual with chondrodysplasia with congenital joint dislocations, <i>CHST3</i>-related. Mild platyspondyly is observed. Note also the coronal clefts throughout the lumbar region.</p></div></div></div></div><div id="bk_toc_contnr"></div></div></div>
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