clinical and genetic analysis subsequently revealed that he and his father were predisposed to hypertrophic cardiomyopathy ( hcm ) : they were carriers of a missense mutation in the -tropomyosin gene .
the boy had no symptoms before he collapsed , whereas his father ( in his early forties ) had borderline myocardial hypertrophy in the interventricular septum associated with mild symptoms of cardiac disease .
a daughter , age 11 , also carried the mutation , but she was entirely asymptomatic . on average , penetrance of
although the familial character of the disorder was suspected for some time prior to this event , genetic counselling had not been considered before the boy experienced cardiac arrest . in a second family the disease was associated with a high frequency of cardiac death .
three documented cases of premature sudden death in two generations , two of them in young adults , and numerous relatives being clinically affected imposed a heavy burden on the family .
early onset of the disease , syncopes , chest pain and progression to heart failure with no , or inconspicuous , hypertrophy were encountered .
all first - degree relatives of the patients were seeking counselling and asked for a dna test .
they were aware that this test offered a 50% chance of excluding the carrier status for those who were asymptomatic , in particular for children of parents at risk .
these are two different disease phenotypes randomly picked from numerous published or unpublished case reports of familial hcm .
this is a heavily investigated disorder for which we have ample knowledge about causes and - to a lesser degree - about mechanisms .
it is autosomal dominant and known to exist worldwide with a prevalence possibly as high as 1:500 in the general population .
it may occur sporadically , but in the majority of cases it is a familial condition .
onset of symptoms is normally encountered during adolescence or in young adults , but first appearances may also be experienced in later decades of life .
symptoms are usually unspecific at first , and may include breathlessness , chest pain , syncopes and others .
the diagnosis is confirmed by echocardiographic demonstration of myocardial hypertrophy , most frequently in the interventricular septum .
diagnostic criteria for the assessment of the disease in members of families at risk have been proposed .
the most serious complication of hcm is ventricular fibrillation , which may cause sudden cardiac death .
a typical problem is the extensive clinical variability of hcm , even within families where all patients have the same mutational background .
more than 100 different mutations ( mostly missense mutations leading to amino acid exchanges in respective proteins ) have been reported .
these mutations are in nine genes , all coding for contractile proteins - cardiac motor proteins and their control components .
the most frequently affected genes , accounting for more than 50% of all cases , coded for -myosin heavy chain , cardiac troponin t and myosin binding protein - c .
mutational hot spots are rare and contribute only a few percent of the total genetic load of hcm .
altered kinetics of cross - bridge cycling of myosin and actin filaments are probably involved .
increased ( or decreased ) sensitivity of force development in response to calcium may be a critical parameter .
other calcium - dependent mechanisms influencing gene expression rather than contraction have also been discussed .
the goals of counselling are , in general , the assessment of causes , which requires genetic testing of probands and family members , the determination of recurrence risks , communication about reproductive options and prenatal diagnosis , if suggested or requested .
the clinical diagnosis of hcm is made by the cardiologist who might then refer patients and families to the geneticist .
genetic tests are performed in specialised labs ( of which only a few exist ) .
the estimate of recurrence risks is easy in most instances , because the usual mode of transmission is known to be dominant .
dominant transmission ( when only one parent is a carrier of the condition ) means the parent has a 50% chance of transmitting the mutation to their offspring .
more challenging , but also rather infrequent , are asymptomatic parents with one affected child , a condition indicative of a new , or de novo , mutation which originated in a single parental gamete .
such a mutation has a negligible chance of re - occurring in siblings , but it can be passed to the next generation by carriers .
hcm is in many cases not a devastating condition and usually it does not produce symptoms in children , unlike duchenne muscular dystrophy or cystic fibrosis .
many gene carriers have a reasonable chance of getting away with minor symptoms and normal life expectancy ( see eg ) ; in some , however , quality of life and longevity may be severely affected .
families have been described where only 50% of gene carriers lived beyond the age of 45 years .
although underlying mutations in these families are statistically characterised as malignant , it is difficult ( if not impossible ) to assign individual risks on the basis of a dna test alone .
thus , in most cases of a positive hcm family history , reproductive decisions are normally not affected .
occasionally it may happen that premature sudden death is a frequent event imposing an unusually high psychosocial and medical burden on a family . in these cases
prospective parents may wish to prevent passing the mutation to their offspring and , hence , ask for a pre - natal dna test with the option to terminate a ' carrier ' pregnancy .
if that information is not available , testing will normally be futile because of the current slow speed of screening genes for unidentified dna changes .
if the mutation is known , a preimplantation diagnosis after in vitro fertilisation may be considered as an alternative to prenatal testing .
in addition to professional counselling by geneticists , a practice of informal communication developed in some institutions since the main reference person for hcm patients and their families is the cardiologist whom they see on a regular basis to control the progression of the disease and the efficacy of therapy . diagnostic efforts require informed consent by the patient ; this consent frequently covers the submission of blood samples to a specialised molecular lab for a dna test , as part of a new clinical routine which should , but which frequently does not , include genetic counsel .
this practice of quasi automatic dna testing may not be the same in all countries , but at least in some places the geneticist is not regularly consulted .
the reason is simply that it is the cardiologist , not the clinical geneticist , who has the main responsibility for the patient .
the recognition that a patient is at high risk depends on identification of clinical markers such as excessive hypertrophy   or nonsustained ventricular tachycardia   rather than on the demonstration of a particular mutation .
normally it is the genetic counsellor , not the clinician , who is trained to explain the meaning of genetic risks in terms understandable to patients .
the burden of the disease must be clearly communicated and reproductive options have to be discussed .
reassurance should be given to those who worry about the consequences of their genetic status .
it may be added that these discussions should also cover health and life insurance problems which will probably become relevant in the future , in particular for those who have no symptoms but who are at risk to be gene carriers .
potential gene carriers with no symptoms may increasingly tend to refuse participation in familial screening to avoid unfavourable terms of insurance , a conflict to which young adults in their early career stages are exposed more than others .
( the strategy of avoiding knowledge about genetic risks would , however , only work in the absence of compulsory testing ) .
they usually have no symptoms , and the test may therefore stigmatise them as gene carriers - in the absence of efficient prevention ( , but see ) .
one should realise , however , that careful investigation of the preclinical stages of hcm will eventually help to advance knowledge of the natural history of the disease - a prerequisite to the development of improved protocols for prevention and therapy of this disorder . at present ,
in the absence of formal constraints to apply dna tests to entire families , it can be foreseen and it seems inevitable that in a growing number of families all gene carriers will become known . as a rule ( with occasional exceptions ) , both cardiologists and parents want to know .
appropriate communication with genetic counsellors should help to alleviate psychosocial and emotional problems associated with the assessment of the carrier status , in particular in the young .
a scheme according to which cardiologists , clinical and molecular geneticists could cooperate in both aspects , counselling patients and managing hcm clinically , is presented in fig .
1 . this scheme emphasises the different branches involved in management and counselling of hcm , with a predominance on the side of clinical activities .
prenatal diagnosis - which in our experience is almost never requested - has not been considered in this scheme as a major topic .
a dna test can confirm the diagnosis ; however , in most cases , a sarcomeric mutation does not by itself fully explain the pathogenic character of the disease .
for one , many families have their own ' private ' mutation , and for another , evidence is accumulating that other components , for example genetic polymorphisms , which contribute to cardiovascular performance without being bona fide disease genes , also affect penetrance and severity of the disease .
it is likely that non - mendelian , multifactorial conditions modify the natural history of hcm   which otherwise is , by definition , a mendelian disorder . the difficulties of drawing firm conclusions from knowledge of a mutation in a distinct disease - related gene should not excuse a lack of competent genetic counselling .
appropriate activities depend on the existence of an organisation comprising cardiologists , a molecular laboratory , and clinical geneticists , as shown in the flow diagram of fig
since , however , knowledge and tools are in principle available , the appropriate answer to the initial question of whether to provide genetic counselling " ready or not " is that there is no good reason not to be ready . a scheme for cooperative interaction between cardiologists , clinical and molecular geneticists and those affected by hcm .
tash , transcoronary ablation of septum hypertrophy ( by alcohol ) ; icd , implantable cardioverter defibrillitor .
 hypertrophic cardiomyopathy ( hcm ) is a dominant genetic disorder of the myocardium associated with dysfunctional contractile proteins . 
 the major risk of hcm is sudden cardiac death , which may occur even in asymptomatic carriers . 
 causes are highly heterogeneous . over 140 different mutations in nine sarcomeric genes have been described to date . 
 the majority of cases ( 80% or more ) may eventually be traced to one of these genes . although genetic counselling is suggested even if mutations are not known , molecular diagnosis implies new options such as carrier identification or - theoretically - preclinical risk stratification . a scheme according to which cardiologists and clinical and molecular geneticists could cooperate in counselling patients and managing hcm clinically is proposed . 
Introduction
Causes and mechanisms
Diagnosis and repercussions
Conclusion