[CRT-FORUM] 46E 4-year-old girl with dilated cardiomyopathy. Dr. Cezimbra

[CRT-INFO]

I would like to congratulate everyone for this outstanding symposium and 
add that this genetic screening would be important for the future 
retatives of this pedriatic patient, being altogether useless for 
herself, since, so far, we can not treat sick genes.
Sincerely,
Alexandre Cezimbra M.D.
<cezimbra at cardiol.br>
> Dear all: I insist that genetic screening is very important in this case
> report.
> Example: Mutations in the PRKAG2 gene that encodes the gamma2 regulatory
> subunit of AMP-activated protein kinase have been shown to cause 
> autosomal
> dominant WPW syndrome associated with HCM. PRKAG2 mutations are 
> responsible
> for a diverse phenotype and not only the familial form of the WPW 
> syndrome.
> Familial occurrence of pseudo appearance of atrial hypertrophy, sinus
> dysfunction, sinus bradycardia, supraventricular extrasystole, short PR
> interval, RBBB and occasionally left anterior fascicular block, and 
> should
> raise suspicion of a mutant PRKAG2 gene. Mutations in this gene are
> associated with familial ventricular WPW, HCM, and SA and AV conduction
> disturbances. Clinico-pathologic and experimental data suggest the
> hypothesis of a glycogen storage disease. PRKAG2 mutations do not 
> cause HCM
> but rather lead to a novel myocardial metabolic storage disease, in which
> hypertrophy, ventricular WPW and conduction system defects coexist(1).
> Sternick et al(2) studied two large families and found a total of 20
> affected individuals showing a combination of sinus bradycardia, short PR
> interval, RBBB, intra and infrahisian conduction disturbances often
> requiring a pacemaker, and atrial tachyarrhythmias. Three individuals 
> died
> suddenly at a young age. No patient had the WPW syndrome, and 10% had
> myocardial hypertrophy. The authors performed screening of the exons and
> exon-intron boundaries of PRKAG2 that revealed a missense mutation
> (Arg302Gln) in the affected individuals from both families. This mutation
> had been associated with the familial form of the WPW syndrome and with a
> high prevalence of LVH. Besides WPW syndrome and HCM, PRKAG2 mutations 
> are
> responsible also for a diverse phenotypes. PRKAG2 gene mutation should be
> suspected with familial occurrence of RBBB, sinus bradycardia, and 
> short PR
> interval(3).
> Another entity is Danon disease: it is clinically characterized by the
> triad;
> 1) HCM or dilatation of all cardiac chambers with impaired systolic and
> diastolic function
> 2) Proximal myopathy
> 3) Mental retardation.
> Myopathy and mental retardation can be absent, It is a dominant X-linked
> disorder. It is due to mutation in gene for lysosome-associated membrane
> protein 2 (LAMP 2). The LAMP 2 gene is located on Xq24, and its mutation
> causes primary deficiency of LAMP 2 and myocyte hypertrophy by 
> accumulations
> of vacuoles containing glycogen. Danon disease is an under-recognized and
> frequently fatal condition, treatable by heart transplantation.
> Investigation of the primary molecular defect is important for cardiac
> surveillance and genetic counseling(4)
>
> References
>
> 1) Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter
> RJ, McGarry K, Seidman JG, Seidman CE. Constitutively active AMP kinase
> mutations cause glycogen storage disease mimicking hypertrophic
> cardiomyopathy. J Clin Invest. 2002 Feb;109:357-362.
>
> 2) Sternick EB, Oliva A, Magalhães LP, Gerken LM, Hong K, Santana O,
> Brugada P, Brugada J, Brugada R. Familial pseudo-Wolff-Parkinson-White
> syndrome. J Cardiovasc Electrophysiol. 2006 Jul; 17:724-732.
>
> 3) Hong K, Oliva A, Cheng XS, Brugada P, Brugada J, Sternick EB,
> Brugada R. Same genotype and different phenotypes in a family with PRKAG2
> gene mutation. Zhonghua Xin Xue Guan Bing Za Zhi. 2007 Jun; 35: 552-554.
>
> 4) Di Blasi C, Jarre L, Blasevich F, Dassi P, Mora M. Danon disease: a
> novel LAMP2 mutation affecting the pre-mRNA splicing and causing aberrant
> transcripts and partial protein expression. Neuromuscul Disord. 2008
> Dec;18:962-966.
>
> All the best for all
> Andrés Ricardo Pérez Riera MD
> Chief of electrovectorcardiographic sector. ABC’s Medical School, ABC
> Foundation, Santo André, São Paulo, Brazil Riera at uol.com.br
>


-- 
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee