**13. What should the genetic counseling be in cardiomyopathy?**

To provide genetic counseling to an individual that has a cardiomyopathy is not an easy task.

When a patient or a relative that has been diagnosed with cardiomyopathy comes for genetic counseling, the geneticist has to be forthright and explain that there are all sorts of disorders that cause it, locus heterogeneity and clinical variability.

It is very important that when a numerical value is provided the patient and/or his family understand what has been explained to them. It is necessary to be very clear that chance does not have a memory. It would be embarrassing to face a family that comes with a second affected child because they have misinterpreted the information provided to them.

It should also be pointed out that the molecular diagnosis of a disorder it is not only time consuming and a very expensive process, but also that, sometimes, there is not a specific mutation that stands out in the different disorders that cause a cardiomyopathy. Many patients do not have an identified causing gene defect.

Opinions differ about procedures when consultants are under 18 and asymptomatic, and at risk of having the disorder when adults, and there is not a causal treatment. Therefore, running the molecular test of the disorder would be inappropriate. If a mutation is found, the children will not longer lead a normal life and it will also have a negative effect on family life.

are at risk of inheriting the mutation. There is not risk that any other family member will inherit

When there are multiple mtDNA deletions the analysis of *RRM2B* should be performed

A prenatal diagnosis for those patients there are at risk for any cardiomyopathy is possible, if

Preimplantation genetic diagnosis (PGD) may be available for families in which the mutation

In spite of the fact that there has been considerable improvement in the molecular diagnosis of the different mutations that lead to cardiomyopathies, we still have to learn more about the

, Onnik Agbulut2

1 Clinical Unit, Department of Genetics, Faculty of Medicine, University of the Republic,

2 University Paris Diderot-Paris , Unit of Functional and Adaptive Biology (BFA) affiliated with CNRS (EAC), Laboratory of Stress and Pathologies of the Cytoskeleton, Paris, France

[1] Aernout Somsen, Kees Hovingh G, Tulevski I. Familial dilated cardiomyopathy. In Baars H, van der Smagt, J, Doevendans P, editors. Clinical Cardiogenetics: Springer

[2] Aleong, R.G., Milan, D.J. & Ellinor, P.T. (2007). The diagnosis and treatment of car‐ diac ion channelopathies: congenital long QT syndrome and Brugada syndrome. Cur

[3] Al-Jassar C, Knowles T, Jeeves M et al. The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations. J Mol Biol. 2011

and Maria-Mirta Rodríguez1

The Role of Genetics in Cardiomyopathy http://dx.doi.org/10.5772/55775 123

the mutation carried by the parents or the proband has been previously identified.

the disease.

**14. Conclusion**

**Author details**

Luis Vernengo1

**References**

Montevideo, Uruguay

2011; p. 63-78.

411:1049-1061.

because it conditions the genetic counseling.

that causes the disorder has already been identified.

pathophysiology of these sometimes deadly disorders.

, Alain Lilienbaum2

Treat Opt in Cardio Med 2007; 9; 5:364-371.

In HCM, the first step the geneticist should take is to order the molecular analyses of *MYH7* and *MYBPC3*, the two genes that carry most of the mutations.

Should the mutations not be in these two genes, the genetic analyses of *TNNT2, TNNT3, MYL2, MYL3, TPM1* and *ACTC* might clarify other cases.

Sometimes, if no mutations are found in any of the genes tested, the disorder cannot be ruled out because it is likely that a new gene not yet discovered can be the cause.

In DCM the mode of inheritance has to be defined in other to provide a correct counseling as the there is locus and allelic heterogeneity.

In the autosomal dominant cardiomyopathies most individuals diagnosed have an affected parent. However, the index case may have the disorder as the result of a *de novo* mutation.

In HCM, it is not known the number of cases that are caused by these *de novo* gene mutations. While in Brugada syndrome and in RWS *de novo* mutations are low, and in CPVT is almost 40%.

Timothy syndrome is due to either a *de novo* mutation or parental germline mosaicism. They do not live long enough to reproduce.

Only the siblings are at risk of inheriting the disorder.

When there is a *de novo* mutation, alternate paternity and maternity as well as whether the patient is adopted have to be ruled out.

The offspring of a patient suffering autosomal dominant familial cardiomyopathy has a 50% chance of inheriting the mutation. Families in which penetrance appears to be incomplete or reduced have been observed; therefore a parent with a mutation that causes the disorder is not affected whereas the son or daughter is. The severity and age of onset cannot be predicted.

The siblings of the index case depend on the genetic condition of their parents. If a parent is affectedorhas themutationthat causes thedisorder,the risk to inheritthemutatedallele is 50%.

In the cases reported where more than one mutation in one the genes encoding a sarcomere protein has been identified in a patient with HCM, it is very difficult to assess the mode of inheritance and makes it arduous for the geneticist to give an accurate risk assessment to another family member.

It is essential to provide patients and relatives that are at risk, the potential risk their offspring might have in these disorders and the reproductive options they have.

In the autosomal recessive traits the parents are obligate carriers. The offspring of a patient suffering an autosomal recessive familial cardiomyopathy will be obligate carriers. The siblings have a 25% chance of inheriting the mutation.

The deletions in mtDNA are usually due to *de novo* mutations, so there is only one family member affected. The offspring of a male patient are not at risk whereas all females´ offspring are at risk of inheriting the mutation. There is not risk that any other family member will inherit the disease.

When there are multiple mtDNA deletions the analysis of *RRM2B* should be performed because it conditions the genetic counseling.

A prenatal diagnosis for those patients there are at risk for any cardiomyopathy is possible, if the mutation carried by the parents or the proband has been previously identified.

Preimplantation genetic diagnosis (PGD) may be available for families in which the mutation that causes the disorder has already been identified.
