**14. Conclusion**

the molecular test of the disorder would be inappropriate. If a mutation is found, the children

In HCM, the first step the geneticist should take is to order the molecular analyses of *MYH7*

Should the mutations not be in these two genes, the genetic analyses of *TNNT2, TNNT3, MYL2,*

Sometimes, if no mutations are found in any of the genes tested, the disorder cannot be ruled

In DCM the mode of inheritance has to be defined in other to provide a correct counseling as

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

When there is a *de novo* mutation, alternate paternity and maternity as well as whether the

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

It is essential to provide patients and relatives that are at risk, the potential risk their offspring

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

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

might have in these disorders and the reproductive options they have.

siblings have a 25% chance of inheriting the mutation.

out because it is likely that a new gene not yet discovered can be the cause.

will not longer lead a normal life and it will also have a negative effect on family life.

and *MYBPC3*, the two genes that carry most of the mutations.

*MYL3, TPM1* and *ACTC* might clarify other cases.

the there is locus and allelic heterogeneity.

122 Cardiomyopathies

do not live long enough to reproduce.

patient is adopted have to be ruled out.

another family member.

Only the siblings are at risk of inheriting the disorder.

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 pathophysiology of these sometimes deadly disorders.
