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<meta name="DC.Title" content="Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome" />
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<meta name="DC.Description" content="SUMMARY: In Joubert syndrome, the “molar tooth” sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia,” referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature.

AMCD
:   anterior mesencephalic cap dysplasia
CST
:   corticospinal tract
IQ
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JS
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SCP
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<meta name="DC.Contributor" content="F. Arrigoni" />
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<meta name="DC.Contributor" content="C. Parazzini" />
<meta name="DC.Contributor" content="E.M. Valente" />
<meta name="DC.Contributor" content="R. Borgatti" />
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<meta name="citation_title" content="Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;SUMMARY:&lt;/h3&gt;
&lt;p&gt;In Joubert syndrome, the “molar tooth” sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the &lt;i&gt;TMEM67&lt;/i&gt; gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia,” referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature.&lt;/p&gt;" />
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<meta name="twitter:title" content="Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome" />
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<meta name="twitter:description" content="SUMMARY: In Joubert syndrome, the “molar tooth” sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia,” referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature.

AMCD
:   anterior mesencephalic cap dysplasia
CST
:   corticospinal tract
IQ
:   Intelligence Quotient
JS
:   Joubert syndrome
SCP
:   superior cerebellar peduncle" />
<meta name="og-title" property="og:title" content="Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome" />
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<meta name="og-description" property="og:description" content="SUMMARY: In Joubert syndrome, the “molar tooth” sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia,” referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature.

AMCD
:   anterior mesencephalic cap dysplasia
CST
:   corticospinal tract
IQ
:   Intelligence Quotient
JS
:   Joubert syndrome
SCP
:   superior cerebellar peduncle" />
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    <div class="highwire-article-citation highwire-citation-type-highwire-article node57346--5" data-node-nid="57346" id="top-node-57346--61094164624" data-pisa="ajnr;38/12/2385" data-pisa-master="ajnr;ajnr.A5360" data-apath="/ajnr/38/12/2385.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Pediatrics</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access hw-icon-open-access" title="Open Access" aria-hidden="true"></i><span  class="element-invisible highwire-access-icon highwire-access-icon-open-access" style="">Open Access</span></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">F. Arrigoni</span>, <span class="highwire-citation-author" data-delta="1">R. Romaniello</span>, <span class="highwire-citation-author" data-delta="2">D. Peruzzo</span>, <span class="highwire-citation-author" data-delta="3">A. De Luca</span>, <span class="highwire-citation-author" data-delta="4">C. Parazzini</span>, <span class="highwire-citation-author" data-delta="5">E.M. Valente</span>, <span class="highwire-citation-author" data-delta="6">R. Borgatti</span> and <span class="highwire-citation-author" data-delta="7">F. Triulzi</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">December 2017,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">38 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">2385-2390; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A5360 </span></div>
  
  
  
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<div id="hw-article-author-popups-top-node-57346--61094164624" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">F. Arrigoni </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Neuroimaging Lab (F.A., D.P., A.D.L.)</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=F.%2BArrigoni%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Arrigoni%20F&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AF.%2BArrigoni%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-5508-1149" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for F. Arrigoni</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">R. Romaniello </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neuropsychiatry and Neurorehabilitation Unit (R.R., R.B.), Scientific Institute Istituto Di Ricovero e Cura a Carattere Scientific Eugenio Medea, Bosisio Parini, Italy</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=R.%2BRomaniello%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Romaniello%20R&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AR.%2BRomaniello%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-8709-6732" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R. Romaniello</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">D. Peruzzo </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Neuroimaging Lab (F.A., D.P., A.D.L.)</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=D.%2BPeruzzo%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Peruzzo%20D&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AD.%2BPeruzzo%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-9480-379X" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for D. Peruzzo</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">A. De Luca </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Neuroimaging Lab (F.A., D.P., A.D.L.)</div><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Information Engineering (A.D.L.), University of Padova, Padova, Italy</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=A.%2BDe%2BLuca%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=De%20Luca%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AA.%2BDe%2BLuca%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-2553-7299" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for A. De Luca</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">C. Parazzini </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Department of Pediatric Radiology and Neuroradiology (C.P.), “V. Buzzi” Children's Hospital, Milan, Italy</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=C.%2BParazzini%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Parazzini%20C&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AC.%2BParazzini%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-0364-8673" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for C. Parazzini</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">E.M. Valente </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Department of Molecular Medicine (E.M.V.), University of Pavia, Pavia, Italy</div><div class='author-affiliation'><span class='nlm-sup'>f</span>Neurogenetics Unit (E.M.V.), Istituto Di Ricovero e Cura a Carattere Scientific Santa Lucia Foundation, Rome, Italy</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=E.M.%2BValente%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Valente%20E&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AE.M.%2BValente%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-0600-6820" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for E.M. Valente</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">R. Borgatti </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>Neuropsychiatry and Neurorehabilitation Unit (R.R., R.B.), Scientific Institute Istituto Di Ricovero e Cura a Carattere Scientific Eugenio Medea, Bosisio Parini, Italy</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=R.%2BBorgatti%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Borgatti%20R&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AR.%2BBorgatti%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0001-8165-4994" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for R. Borgatti</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">F. Triulzi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>g</span>Department of Neuroradiology (F.T.), Scientific Institute Istituto Di Ricovero e Cura a Carattere Scientific Cà Granda Foundation—Ospedale Maggiore Policlinico, Milan, Italy.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=F.%2BTriulzi%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Triulzi%20F&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AF.%2BTriulzi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-5428-7217" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for F. 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    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>SUMMARY:</strong> In Joubert syndrome, the “molar tooth” sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8–14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the <em>TMEM67</em> gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name “anterior mesencephalic cap dysplasia,” referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATIONS:</h2><dl id="def-list-1"><dt id="def-item-1">AMCD<span class="def-item-dt-sep"></span></dt><dd>anterior mesencephalic cap dysplasia<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">CST<span class="def-item-dt-sep"></span></dt><dd>corticospinal tract<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">IQ<span class="def-item-dt-sep"></span></dt><dd>Intelligence Quotient<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">JS<span class="def-item-dt-sep"></span></dt><dd>Joubert syndrome<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">SCP<span class="def-item-dt-sep"></span></dt><dd>superior cerebellar peduncle</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2017 by American Journal of Neuroradiology</li></ul><div class="license" id="license-1"><p id="p-1">Indicates open access to non-subscribers at <a href="http://www.ajnr.org" rel="license">www.ajnr.org</a></p></div><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/38/12/2385.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
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        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 38</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 12 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Dec 2017 </div></div>
      
      
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      <div class="highwire-cite-title">Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome</div>  
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    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Dec 2017, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">38 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(12) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">2385-2390; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A5360 </span></div>
  
  
  
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