Familial multiple cavernous malformation syndrome
Updates to Article Attributes
The familial multiple cavernous malformation syndrome, or familial cerebral cavernous malformation syndrome, is is uncommon, accounting for only a minority of cavernous malformations.
Epidemiology
It has been more frequently reported in patients of Hispanic descent 1.
Diagnosis
The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following 4,5:
-
multiple cerebral cavernous malformations
five or more cavernomas, or
one cavernoma and at least one other family member with one or more cavernomas
mutations in one of the three genes, KRIT1, CCM2 or PDCD10, which are associated with this disease
Clinical presentation
The presentation is most commonly with seizures (38-55%)1 and and focal neurological deficits, whilst recurrent large haemorrhages and headaches are less frequently encountered.
Cutaneous lesions, including cherry haemangiomas and café au lait spots, are occasionally associated, including 6. :
hyperkeratotic cutaneous capillary-venous malformations
punctate capillary malformations
deep blue nodules
Pathology
In sporadic cases, up to a 3rd ofarewill have multiple. When familial, the number of cavernomas is higher, typically five or more 1 and may be as high as dozens and dozensinnumerable.
Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance 1,2.
See: Zabramski classification of cerebral cavernomas.
Radiographic features
The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain.
For a discussion of the radiographic appearances see: cavernous malformations.
Differential diagnosis
The differential is that of other causes of cerebral microhaemorrhages, including mainly 2:
cerebral amyloid angiopathy: usually numerous small foci
chronic hypertensive encephalopathy: more common in the basal ganglia
MRI appearance may be mimicked by:
artificial heart valve metallic emboli (very rare)pneumocephalus(very rare)3
-<p>The <strong>familial multiple cavernous malformation syndrome</strong>, or <strong>familial cerebral cavernous malformation syndrome</strong>, is uncommon, accounting for only a minority of <a href="/articles/cerebral-cavernous-venous-malformation">cavernous malformations</a>.</p><h4>Epidemiology</h4><p>It has been more frequently reported in patients of Hispanic descent <sup>1</sup>.</p><h4>Diagnosis</h4><p>The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following <sup>4,5</sup>:</p><ul>-<li>-<p>multiple cerebral cavernous malformations</p>-<ul>-<li><p>five or more cavernomas, or</p></li>-<li><p>one cavernoma and at least one other family member with one or more cavernomas</p></li>-</ul>-</li>-<li><p>mutations in one of the three genes, <em>KRIT1</em>, <em>CCM2</em> or <em>PDCD10</em>, which are associated with this disease</p></li>-</ul><h4>Clinical presentation</h4><p>The presentation is most commonly with seizures (38-55%) <sup>1</sup> and focal neurological deficits, whilst recurrent large haemorrhages and headaches are less frequently encountered. </p><p>Cutaneous lesions, including cherry haemangiomas and café au lait spots, are occasionally associated <sup>6</sup>. </p><h4>Pathology</h4><p>In sporadic cases up to a 3<sup>rd</sup> of cavernous malformations are multiple. When familial the number of cavernomas is higher, typically five or more <sup>1</sup> and may be as high as dozens and dozens.</p><p>Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance <sup>1,2</sup>. </p><p>See: <a href="/articles/zabramski-classification-of-cerebral-cavernous-malformations">Zabramski classification of cerebral cavernomas</a>.</p><h4>Radiographic features</h4><p>The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain. </p><p>For a discussion of the radiographic appearances see: <a href="/articles/cerebral-cavernous-venous-malformation">cavernous malformations</a>.</p><h4>Differential diagnosis</h4><p>The differential is that of other causes of <a href="/articles/cerebral-microhaemorrhage">cerebral microhaemorrhages</a>, including <sup>2</sup>:</p><ul>-<li><p><a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy</a>: usually numerous small foci</p></li>-<li><p><a href="/articles/chronic-hypertensive-encephalopathy">chronic hypertensive encephalopathy</a>: more common in the basal ganglia</p></li>-<li><p><a href="/articles/diffuse-axonal-injury-dai">diffuse axonal injury (DAI)</a></p></li>-<li><p><a href="/articles/cerebral-vasculitis">cerebral vasculitis</a></p></li>-<li><p><a href="/articles/radiation-vasculopathy">radiation vasculopathy</a></p></li>-<li><p><a href="/articles/haemorrhagic-intracranial-metastases">haemorrhagic metastases</a></p></li>-<li><p><a href="/articles/parry-romberg-syndrome">Parry-Romberg syndrome</a> <sup>2</sup></p></li>-</ul><p>MRI appearance may be mimicked by:</p><ul>-<li><p>artificial heart valve metallic emboli (very rare)</p></li>-<li><p><a href="/articles/pneumocephalus">pneumocephalus</a> (very rare) <sup>3</sup></p></li>- +<p>The <strong>familial multiple cavernous malformation syndrome</strong>, or <strong>familial cerebral cavernous malformation syndrome</strong>, is uncommon, accounting for only a minority of <a href="/articles/cerebral-cavernous-venous-malformation">cavernous malformations</a>.</p><h4>Epidemiology</h4><p>It has been more frequently reported in patients of Hispanic descent <sup>1</sup>.</p><h4>Diagnosis</h4><p>The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following <sup>4,5</sup>:</p><ul>
- +<li>
- +<p>multiple cerebral cavernous malformations</p>
- +<ul>
- +<li><p>five or more cavernomas, or</p></li>
- +<li><p>one cavernoma and at least one other family member with one or more cavernomas</p></li>
- +</ul>
- +</li>
- +<li><p>mutations in one of the three genes, <em>KRIT1</em>, <em>CCM2</em> or <em>PDCD10</em>, which are associated with this disease</p></li>
- +</ul><h4>Clinical presentation</h4><p>The presentation is most commonly with seizures (38-55%) <sup>1</sup> and focal neurological deficits, whilst recurrent large haemorrhages and headaches are less frequently encountered. </p><p>Cutaneous lesions are occasionally associated, including <sup>6</sup>: </p><ul>
- +<li><p>hyperkeratotic cutaneous capillary-venous malformations</p></li>
- +<li><p>punctate capillary malformations</p></li>
- +<li><p>deep blue nodules</p></li>
- +</ul><h4>Pathology</h4><p>In sporadic cases, up to one-third of cases of cavernous malformations will have multiple. When familial, the number of cavernomas is higher, typically five or more <sup>1</sup> and may be innumerable.</p><p>Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance <sup>1,2</sup>. </p><p>See: <a href="/articles/zabramski-classification-of-cerebral-cavernous-malformations">Zabramski classification of cerebral cavernomas</a>.</p><h4>Radiographic features</h4><p>The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain. </p><p>For a discussion of the radiographic appearances see: <a href="/articles/cerebral-cavernous-venous-malformation">cavernous malformations</a>.</p><h4>Differential diagnosis</h4><p>The differential is that of other causes of <a href="/articles/cerebral-microhaemorrhage">cerebral microhaemorrhages</a>, including mainly <sup>2</sup>:</p><ul>
- +<li><p><a href="/articles/cerebral-amyloid-angiopathy-1">cerebral amyloid angiopathy</a>: usually numerous small foci</p></li>
- +<li><p><a href="/articles/chronic-hypertensive-encephalopathy">chronic hypertensive encephalopathy</a>: more common in the basal ganglia</p></li>
- +<li><p><a href="/articles/diffuse-axonal-injury-dai">diffuse axonal injury</a></p></li>
- +<li><p><a href="/articles/cerebral-vasculitis">cerebral vasculitis</a></p></li>
- +<li><p><a href="/articles/radiation-vasculopathy">radiation vasculopathy</a></p></li>
- +<li><p><a href="/articles/haemorrhagic-intracranial-metastases">haemorrhagic metastases</a></p></li>
References changed:
- 6. Manole A, Forrester V, Zlotoff B, Hart B, Morrison L. Cutaneous Findings of Familial Cerebral Cavernous Malformation Syndrome Due to the Common Hispanic Mutation. Am J Med Genet A. 2020;182(5):1066-72. <a href="https://doi.org/10.1002/ajmg.a.61519">doi:10.1002/ajmg.a.61519</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/32100472">Pubmed</a>
- 6. Clatterbuck R & Rigamonti D. Cherry Angiomas Associated with Familial Cerebral Cavernous Malformations. Case Illustration. J Neurosurg. 2002;96(5):964. <a href="https://doi.org/10.3171/jns.2002.96.5.0964">doi:10.3171/jns.2002.96.5.0964</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/12005409">Pubmed</a>
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