Research Blog Series Recap

For the month of October, PCHA recognized the importance of Research. All different kinds of research are vital to finding a treatment and an eventual cure for CHD and we thank all the clinicians, scientists, and patient volunteers for their important contributions to CHD research. The fight to conquer CHD is strengthened by the involvement of all of those who share our mission. It takes a community coming together around education, research and awareness to make an impact. Volunteer, join our advocacy network today, and connect with us on Facebook! In case you missed a post, below is the full Research Blog series:

The Importance of CHD Surveillance

Psychosocial Functioning of Adolescents with D-Transposition of the Great Arteries

Genetics and Genomics Research – Why It Matters

Genetic Link Between CHD and Neurodevelopmental Disorders

Why Should My Child Participate in Clinical Research?

Research Matters: Genetics and Genomics Research – Why It Matters

research mattersThis week, PCHA focuses on genetics and genomics research and discusses why these studies are important for understanding the underlying genetic causes of CHD. At some point during a hospital visit, you may have been asked to enroll your child in a genetic study. To help parents and caregivers make a more informed decision about whether or not to participate in a genetic study, PCHA provides an overview of some of the genetic concepts and terms that you will read and hear about when discussing this type of study with a coordinator.

Genetics and Genomics Research – Why It Matters

As parents of a child with congenital heart disease (CHD), we are often left wondering why our child was born with this condition. Even though heart defects are the most common birth defect, shockingly little is actually known about what causes CHD. Although many hospitals and laboratories around the world are tackling the problem of CHD, it turns out that one of the most valuable resources in the fight against CHD is our DNA. DNA is the genetic material that contains all of the instructions for how we develop and grow and what we eventually become. The entirety of one’s DNA is called a genome and everyone’s genome is unique. In most cases, the genome holds important clues about the cause of your child’s CHD.

Why is our DNA so important for CHD research?

Although many factors not related to genetics can increase the risk of heart defects, it is likely that genetics plays a major role in most cases of CHD. The instructions for building a heart are contained in our genes. A gene is a segment of DNA that serves as a blueprint for building a specific protein. Every protein has a specific function and the proper development and function of the heart relies on thousands of different proteins. Therefore, a harmful mutation in a gene that is essential for heart development could be a potential cause of CHD.

How did my child get a mutation?

A mutation is any kind of change in DNA and mutations can be inherited or occur spontaneously in a developing unborn child. In fact, new mutations, which are called de novo mutations, happen in every generation. Although most of these mutations are harmless, some mutations can cause disease. It is the identification of these mutations that will be critically important for understanding why certain children are born with CHD.

How are these mutations identified?

There are several studies that have begun to look at the impact of genetics on CHD. One of the largest is the Congenital Heart Disease Genetic Network Study (CHD GENES). In this NIH-funded study, a small sample of blood is collected from you and your child in order to isolate DNA and determine its sequence. DNA is made up of four building blocks called nucleotides and sequencing is the process by which the exact order of nucleotides that make up the DNA is determined. In whole genome sequencing, the sequence of one’s entire DNA is determined. In whole exome sequencing, only the segments of DNA that code for proteins are sequenced. Sequencing allows for the detection of mutations that could be potentially harmful for your child.

Why is it important that all of us participate in genomics research?

Although CHD is the most common birth defect, it is important to remember that the most complex types of CHD are rare. A mutation in any one of hundreds of genes could potentially cause CHD. Furthermore, two children with the same heart defect could have mutations in different genes. So even if a mutation is found in your child, it is not easy to assign that mutation as the cause of disease. However, if a gene that is mutated in your child is also mutated in many other children with CHD, then it becomes more and more likely that the mutation is responsible for the disease. As the number of people in the study increases, it becomes easier to identify the genes involved in CHD. This type of study is called a genome-wide association study (GWAS) and these studies become more powerful when more people participate.

Why is it important that both parents participate in genomics research?

In many cases, children with a heart defect are born to parents without a family history of CHD. Oftentimes, a de novo mutation is responsible for the disease. This is one reason why many research studies encourage the participation of both parents. By comparing the DNA sequence of the child with the DNA sequences of both parents, it becomes easier to spot new mutations in the child since neither parent will carry the mutation.

What happens if a mutation is identified in my child?

It is important to understand that the identification of a mutation will not lead to an immediate cure. However, it could have many potential implications for the long-term health and development of your child as well as future generations of children born with CHD. For example, many genes that are important for heart development are also important for the development of other organs in the body like the brain and kidney. This might explain why so many children with CHD experience neurodevelopmental delay as well as other non-heart-related health issues. Knowing which gene is affected in your child can help diagnose other problems and allow for earlier intervention. Furthermore, many children with CHD have progressive conditions and understanding the genetics of their disease will be absolutely critical for the discovery of drugs that can stem the tide of the disease. Finally, parents who receive an earlier CHD diagnosis will be well informed and more prepared to care for their child. It is important to remember that science and medicine are advancing at a rapid pace. There is hope for children with CHD and understanding the genes that are important for heart development and function will be the key to conquering this disease.

How can we participate?

Participation in any research study is entirely voluntary. Privacy issues are usually the main concern of parents, but, in most cases, many steps are taken to ensure the privacy of the parents and your child. This and any other issue can be discussed with the clinical coordinator before you enroll in a study. To participate specifically in the CHD GENES study mentioned above, a list of participating centers can be found here.


michael_kim_photo

Michael Kim is a scientist and a father of two little girls. His oldest daughter Sydney was born with total anomalous pulmonary venous return (TAPVR) in 2011. He received his B.A. in Biochemistry from the University of California, Berkeley and his Ph.D. in Cell and Structural Biology from the University of Illinois, Urbana-Champaign. He and his family currently live in Miami, FL.

Research Matters: An Innovative Treatment for Plastic Bronchitis – What it Means

research matters

The Pediatric Congenital Heart Association is thrilled to bring our latest in the series titled Research Matters. In our commitment to make research meaningful and accessible to patients and families, volunteers along with members of our Medical Advisory Board have created summaries of important research and describe what it means for you.

Plastic bronchitis (PB) is a rare but life-threatening complication that can arise following the Fontan procedure. PB patients develop large, rubbery plugs or “casts” that obstruct the airways and can lead to asphyxiation. Problems of the lymphatic system, a network of organs and vessels that drains fluid (lymph) from tissues and protects the body from infection, are thought to play a role in the disease process, but how PB develops remains poorly understood. The journal Circulation recently published a study reporting findings of abnormal circulation of lymph fluid in most patients with surgically corrected congenital heart disease (CHD) and PB and significant improvement of symptoms in these patients following interventional approaches to block the abnormal flow of lymph. These findings highlight an innovative procedure that has the potential to offer significant long-term improvement of symptoms in patients with PB. You can view the abstract here.

About this Study:
  • This retrospective study expands on a previous case report1 and determines the extent of abnormalities in the lymphatic system of PB patients and the clinical response following interventions to block improper lymphatic flow. A retrospective study looks back in time using existing medical data and records.
  • The retrospective case series comprises 18 patients (between the ages of two and 15) with PB and surgically corrected CHD who underwent lymphatic imaging and interventions at the Children’s Hospital of Philadelphia.
  • The authors use advanced lymphatic imaging tests, including dynamic contrast-enhanced magnetic resonance (MR) lymphangiography to determine the anatomy of the patients’ lymphatic systems and the patterns of lymphatic flow.
Main Findings:
  • In 16 of 18 patients, lymphatic imaging revealed abnormal (retrograde) flow of lymph fluid from the thoracic duct into lung tissue.
  • Lymphatic embolization, a procedure that seals leaks in the lymphatic system using coils, special oil-based contrast agents or glue, was performed in 17 of 18 patients.
  • Significant improvements in PB symptoms were observed in 15 of the 17 patients who underwent lymphatic embolization at a median follow-up of 315 days.
  • Immediate complete resolution of PB symptoms was reported in 10 of 16 patients, with one patient being cast-free for over two years.
What this Means:
  • Abnormal pulmonary lymphatic flow, which the authors termed pulmonary lymphatic perfusion syndrome, is likely to be a major underlying cause of PB in Fontan patients with elevated central venous pressure (CVP).
  • Advances in lymphatic imaging tests will enable the detection of lymphatic flow disorders in PB patients that may go undetected using conventional methods.
  • Selective lymphatic embolization provides a safe and effective alternative to surgical thoracic duct ligation, which has also been used to treat PB.
  • Although short-term results are encouraging, the medium- and long-term effects of lymphatic embolization in PB patients remain unknown. A study that follows patients over a period of years (a longitudinal study) will be required to determine long-term outcomes of this treatment.
  • This study provides hope for PB patients and favorable long-term treatment outcomes have the potential to mitigate the need for heart transplantation in sufferers of PB.

1 Dori Y, Keller MS, Rychik J, and Itkin M. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient. Pediatrics. 2014;134:e590-e595.

 

michael_kim_photo

Michael Kim is a scientist and a father of two little girls. His oldest daughter Sydney was born with total anomalous pulmonary venous return (TAPVR) in 2011. He received his B.A. in Biochemistry from the University of California, Berkeley and his Ph.D. in Cell and Structural Biology from the University of Illinois, Urbana-Champaign. He and his family currently live in Miami, FL.