Recently identified genetic heart disorder often deadly for young patients

March 24, 2009

A study that included young patients with a recently recognized rare type of cardiomyopathy (a disorder of the heart muscle) linked to a genetic mutation finds that progression of this disease may be rapid and often results in early death, according to a study in the March 25 issue of JAMA.

Mutations in the lysosome-associated membrane protein gene (LAMP2; known as Danon disease) produce a in young that clinically is similar to severe hypertrophic cardiomyopathy (HCM; a condition in which the muscle becomes thick, making it harder for blood to leave the heart, forcing the heart to work harder to pump blood). However, the natural course of Danon disease has been unclear, according to background information in the article.

Barry J. Maron, M.D., of the Minneapolis Heart Institute Foundation, Minneapolis, and colleagues assessed the natural history associated with LAMP2 cardiomyopathy and the outcomes of diagnostic and management strategies. The study included seven patients (6 boys) who were ages 7-17 years at the time of diagnosis with LAMP2 mutations. Clinical diagnosis in 6 patients occurred as a result of a heart murmur, family screening and findings on routine electrocardiogram (ECG) or by symptoms (chest pain or fainting) and, in 1 patient, by atrial fibrillation ().

During the subsequent average time of 8.6 years after diagnosis, each of the 7 patients experienced serious adverse clinical consequences by 14 to 24 years of age (average, 21 years). Four patients died of acute or progressive heart failure, and 1 patient underwent . Clinical deterioration was often rapid, with the time interval from clinical stability with little or no symptoms to end-stage heart failure as brief as 6 months. Two other patients experienced sudden unexpected major arrhythmic events, with one patient dying suddenly (age 14 years) from ventricular fibrillation (very rapid, uncoordinated contractions of the ventricles) that was not responding to implantable cardioverter-defibrillator (ICD) therapy.

All seven patients developed left ventricular systolic (contraction of the left ventricle) dysfunction. All patients had received ICDs, which ultimately failed to terminate lethal ventricular tachyarrhythmias (an excessively rapid heartbeat accompanied by an irregular heartbeat) in five patients. The most recent echocardiographic studies obtained of the patients demonstrated marked left ventricular hypertrophy (enlargement) in each. Postmortem examination of 2 hearts showed massive cardiac hypertrophy.

"The clinical course of these 7 patients with LAMP2 mutations provides important insights regarding molecular diagnosis as well as the natural history, pathophysiology, and clinical implications of this recently recognized genetic cardiomyopathy. LAMP2 mutations cause a particularly profound and accelerated cardiac disease process characterized by clinical deterioration and early death, perhaps representing one of the most lethal cardiomyopathies in young and usually male patients. Such an outcome occurred in the patients in our study despite application of the most contemporary treatment strategies, including the ICD …" the authors write.

"The early experience with the distinctive natural history and prognosis of patients with LAMP2 mutations establishes the importance of molecular diagnosis and underscores the utility of genetic testing."

More information: JAMA. 2009;301[12]:1253-1259.

Source: JAMA and Archives Journals (news : web)

Related Stories

Recommended for you

Genome analysis with near-complete privacy possible, say researchers

August 17, 2017
It is now possible to scour complete human genomes for the presence of disease-associated genes without revealing any genetic information not directly associated with the inquiry, say Stanford University researchers.

Science Says: DNA test results may not change health habits

August 17, 2017
If you learned your DNA made you more susceptible to getting a disease, wouldn't you work to stay healthy?

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Evolved masculine and feminine behaviors can be inherited from social environment

August 15, 2017
The different ways men and women behave, passed down from generation to generation, can be inherited from our social environment - not just from genes, experts have suggested.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.