A 32 year-old woman was referred to our center in 2015. She was apparently healthy but was advised to visit a cardiologist because she had donated eggs some years before and one boy conceived using her gametes had died with heart failure in the context of early onset dilated cardiomyopathy and immune deficiency. A genetic test was performed in the child finding a variant in TAZ (c.583+5G>A) that confirmed the suspected diagnosis of Barth syndrome and a second variant in KCNE2 (c.170T>C) that was considered of unknown significance.  

A complete cardiac investigation including electrocardiogram, imaging, Holter monitoring and stress test was performed without any pathological findings. Targeted genetic testing confirmed she carried both variants identified in the child. In the three-generation pedigree it was remarkable the presence of premature death in boys during neonatal period or early childhood (figure 1). Her mother and sister also carried both variants without any cardiac phenotype. She performed preimplantation diagnostic testing having a healthy child.  

Using donor gametes to achieve pregnancy has increased its frequency as a fertility treatment option. The European Society for Human Genetics (ESHG) does not have a specific guideline for gamete donor screening, although recognize the importance of genetic screening in gamete donation and recommends basic testing for donors to minimize risks of transmitting genetic disorders. The extent of the screening, usually limited to cystic fibrosis, spinal muscular atrophy and certain hemoglobinopathies, is a subject of ongoing debate. 

The transmission of inherited cardiac diseases in the context of gamete donation has been rarely reported although it could be underrecognized. Maron et al. reported the clinical case and implications of hypertrophic cardiomyopathy transmitted by sperm donation to recipients. The donor was completely healthy and his diagnosis was made only after phenotypically expression of the disease was identified in an offspring. The authors point to the need of discussion on the risks of transmitting genetic disease in this context and evaluate the possibility of screening strategies. 

Available donor screening guidelines usually recommend obtaining family history,  although this strategy could not be sufficient in many cases. Most Mendelian forms of cardiac diseases are autosomal dominant with the presence of affected individuals across generations. However, incomplete penetrance and variable expression can difficult the evaluation. Also, the absence of familial disease does not exclude a genetic origin in the case of X-linked and recessive disorders. Moreover, the inheritance pattern should raise the suspicion of specific genetic etiologies as occurred in our case (figure 2).