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(New page: {{Noncompaction cardiomyopathy}} {{CMG}} ==Overview== Noncompaction cardiomyopathy appears to have a genetic basis. Several mutations have been identified. There are more males with NCC t...)
 
 
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==Overview==
==Overview==
Noncompaction cardiomyopathy appears to have a genetic basis. Several mutations have been identified. There are more males with NCC than females which suggests a X linked pattern of inheritance in some patients.
Noncompaction cardiomyopathy can appear sporadically or can be familial.  Although mutations responsible for the sporadic cases have not been identified, several mutations that appear responsible for the familial transmission have been identified<ref>Zambrano  E,  Marshalko  SJ,  Jaffe  CC, et al.  Isolated noncompaction of the ventricular myocardium:  clinical and molecular aspects of a rare cardiomyopathy. Lab Invest.  2002;  82:  117–122.</ref> . 18% <ref>Oechslin  EN,  Attenhofer Jost  CH,  Rojas  JR, et al.  Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol.  2000;  36:  493–500.</ref> to 50%<ref>Chin  TK,  Perloff  JK,  Williams  RG, et al.  Isolated noncompaction of left ventricular myocardium:  a study of eight cases. Circulation.  1990;  82:  507–513.</ref> of family members are affected. There is predominantly an [[autosomal dominant]] mode of inheritance. There are more males with NCC than females which suggests a [[X linked pattern]] of inheritance in some patients. Noncompaction of ventricular myocardium was recently included in the 2006 classification of [[cardiomyopathy|cardiomyopathies]] as a genetic cardiomyopathy <ref name= AHA>{{Cite journal | last =Maron| first =Barry. | last2 =Towbin | first2 =Jeffrey. | last3 =Thiene| first3 =Gaetano | last4 =Antzelevitch| first4 =Charles  | last5 =Corrado| first5 =Domenico. | title = Contemporary Definitions and Classification of the Cardiomyopathies  | journal = American Heart Association Journals  | publisher = American Heart Association t  | volume = 113 | issue =14 | pages =| year =2006 | url= http://circ.ahajournals.org/cgi/content/full/113/14/1807| format = webpage | id = 113:1807-1816}}</ref>.


==Genetics==
==Patterns of Inheritance==
Noncompaction of ventricular myocardium was recently included in the 2006 classification of [[cardiomyopathy|cardiomyopathies]] as a genetic cardiomyopathy <ref name= AHA>{{Cite journal | last =Maron| first =Barry. | last2 =Towbin | first2 =Jeffrey. | last3 =Thiene| first3 =Gaetano | last4 =Antzelevitch| first4 =Charles | last5 =Corrado| first5 =Domenico. | title = Contemporary Definitions and Classification of the Cardiomyopathies | journal = American Heart Association Journals  | publisher = American Heart Association t  | volume = 113 | issue =14 | pages =| year =2006 | url= http://circ.ahajournals.org/cgi/content/full/113/14/1807| format = webpage | id = 113:1807-1816}}</ref>.  
The majority of the time the pattern of inheritance is [[autosomal dominant]]. In some families, the mode of transmission appears to be [[x-linked]]<ref>Bleyl  SB,  Mumford  BR,  Brown-Harrison  MC, et alXq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.</ref> or via mitochondrial transmission.


==Genes Involved==
Several potential genetic abnormalities have been identified:
Several potential genetic abnormalities have been identified:
*One defect is in the gene that encodes for [[alpha-dystrobrevin]].  This is a [[dystrophin-associated protein]] which has been mapped to [[chromosome 18q12]]. The role of this protein is to preserve the structural integrity of the muscle membrane.
*The gene that encodes for [[alpha-dystrobrevin]]<ref>Ichida  F,  Tsubata  S,  Bowles  KR, et al.  Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation.  2001;  103:  1256–1263.</ref>.  This is a [[dystrophin-associated protein]] which has been mapped to [[chromosome 18q12]]. The role of this protein is to preserve the structural integrity of the muscle membrane.
*There is a second X-linked genetic defect which involves a mutation in the gene G4.5 (TAZ), the same gene involved in [[Barth syndrome]]. As a result, some patients with NCC have features of [[Barth syndrome]].  This gene which encodes for [[tafazzin]].
*An X-linked genetic defect which involves a mutation in the gene G4.5 (TAZ) of the Xq28 chromosome region (a gene which encodes for [[tafazzin]]), the same region of the chromosome involved in several [[myopathies]] with cardiac involvement are located. These include [[Barth syndrome]]<ref>Bleyl  SB,  Mumford  BR,  Brown-Harrison  MC, et al.  Xq28-linked noncompaction of the ventricular myocardium:  prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.</ref>, [[Emery-Dreifuss muscular dystrophy]], and [[myotubular myopathy]]. As a result, some patients with NCC may have features of [[Barth syndrome]].   
* Mutations of the [[ryanodine receptor 2 gene]] ([[RyR2]]) as has been seen in patients with [[arrhythmogenic right ventircular dysplasia]].
* Mutations of the [[ryanodine receptor 2 gene]] ([[RyR2]]) as has been seen in patients with [[arrhythmogenic right ventricular dysplasia]].
* Deletions of the [[FKBP12 gene]] result in noncompaction in the mouse.
* Deletions of the [[FKBP12 gene]] result in noncompaction in the mouse<ref>Rigopoulos  A,  Rizos  IK,  Aggeli  C, et al.  Isolated left ventricular noncompaction:  an unclassified cardiomyopathy with            severe prognosis in adults. Cardiology. 2002;98:25–32.</ref>.
*Knockout of the [[Peg1]] gene has been associated with NCC in the mouse <ref>Rigopoulos  A,  Rizos  IK,  Aggeli  C, et al.  Isolated left ventricular noncompaction:  an unclassified cardiomyopathy with                                    severe prognosis in adults. Cardiology.  2002;  98:  25–32.</ref>.
* [[LMNA]] mutations
* [[LMNA]] mutations
*Abnormalities of trnascription factors such as NKX2.5 and TBX5.
*Abnormalities of transcription factors such as [[NKX2.5]] and [[TBX5]].
*Abnormalities of 11p15 as suggested in a GWAS analysis.
*Abnormalities of 11p15 as suggested in a [[GWAS]] analysis.
*22q11 deletion
*22q11 deletion
 
*Distal 5q deletion involving the [[CSX]] gene <ref>Pauli  RM, Scheib-Wixted  S,  Cripe  L, et al.  Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet. 1999;85:419–423.</ref>
The majority of the time the pattern of inheritance is [[autosomal dominant]]. In some families, the mode of transmission appears to be x-linked or via mitochondrial transmission.


==References==
==References==

Latest revision as of 14:38, 6 August 2011

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Noncompaction cardiomyopathy can appear sporadically or can be familial. Although mutations responsible for the sporadic cases have not been identified, several mutations that appear responsible for the familial transmission have been identified[1] . 18% [2] to 50%[3] of family members are affected. There is predominantly an autosomal dominant mode of inheritance. There are more males with NCC than females which suggests a X linked pattern of inheritance in some patients. Noncompaction of ventricular myocardium was recently included in the 2006 classification of cardiomyopathies as a genetic cardiomyopathy [4].

Patterns of Inheritance

The majority of the time the pattern of inheritance is autosomal dominant. In some families, the mode of transmission appears to be x-linked[5] or via mitochondrial transmission.

Genes Involved

Several potential genetic abnormalities have been identified:

References

  1. Zambrano E, Marshalko SJ, Jaffe CC, et al. Isolated noncompaction of the ventricular myocardium: clinical and molecular aspects of a rare cardiomyopathy. Lab Invest. 2002; 82: 117–122.
  2. Oechslin EN, Attenhofer Jost CH, Rojas JR, et al. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol. 2000; 36: 493–500.
  3. Chin TK, Perloff JK, Williams RG, et al. Isolated noncompaction of left ventricular myocardium: a study of eight cases. Circulation. 1990; 82: 507–513.
  4. Maron, Barry.; Towbin, Jeffrey.; Thiene, Gaetano; Antzelevitch, Charles; Corrado, Domenico. (2006). "Contemporary Definitions and Classification of the Cardiomyopathies" (webpage). American Heart Association Journals. American Heart Association t. 113 (14). 113:1807-1816.
  5. Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.
  6. Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001; 103: 1256–1263.
  7. Bleyl SB, Mumford BR, Brown-Harrison MC, et al. Xq28-linked noncompaction of the ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals. Am J Med Genet. 1997; 72:257–265.
  8. Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002;98:25–32.
  9. Rigopoulos A, Rizos IK, Aggeli C, et al. Isolated left ventricular noncompaction: an unclassified cardiomyopathy with severe prognosis in adults. Cardiology. 2002; 98: 25–32.
  10. Pauli RM, Scheib-Wixted S, Cripe L, et al. Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet. 1999;85:419–423.


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