Hypoplastic left heart syndrome likely caused by genetic factors

Published on October 11, 2007 at 12:01 AM · 17 Comments

Hypoplastic Left Heart Syndrome (HLHS), a severe cardiovascular malformation that is difficult to treat and often lethal, is caused primarily by genetic factors, according to a new study by researchers at Cincinnati Children's Hospital Medical Center.

The study – to be published in the Oct. 16 edition of the Journal of the American College of Cardiology – is the first to show the high heritability and likely genetic underpinnings of HLHS and recommend a direction for future research into its cause, development and possible therapeutic strategies.

“Our study demonstrates that HLHS has high heritability, suggesting it is caused almost entirely by genetic effects instead of environmental factors, and that families with a child with HLHS carry a significant recurrence risk of HLHS or related heart defects. This should be considered by physicians when counseling parents to ensure they are aware of potential risks,” said Robert B. Hinton, Jr., M.D., a physician and researcher at Cincinnati Children's and the study's lead author.

HLHS is rare, occurring in about two of every 10,000 children born, Dr. Hinton said. Of those children born with HLHS approximately 20 percent die during the first months of life, he added. Children with HLHS suffer from restricted blood and oxygen flow because their hearts are abnormally shaped with an underdeveloped left side. This can include an undersized and/or malformed left ventricle (the heart's primary pumping chamber), aorta, aortic valve or mitral valve. Despite significant advances in diagnosis and therapy, the condition remains challenging to treat and the specific causes remain unknown, Dr. Hinton said. Babies can survive HLHS by undergoing a series of three complex operations after birth or receiving a heart transplant.

The study at Cincinnati Children's included 38 family-based test groups with a history of HLHS. Researchers found that 55 percent of those families had one or more blood relative with HLHS or an associated heart defect. Of 193 blood relatives evaluated between the ages of 3 days and 74 years, 21.4 percent had HLHS or associated heart defects. In families where one child already had HLHS, the risk of HLHS recurring in a sibling was 8 percent while the risk of a sibling having an HLHS-associated cardiovascular defect was 22 percent. In families where a child and one parent had HLHS, the recurrence risk increased dramatically to 21 percent for recurring HLHS and 25 percent for an associated defect. All participants were evaluated using echocardiography to determine specific phenotype, or the visible heart characteristics and defects found among the different family test groups. During those examinations researchers diagnosed 12 new cases of associated defects among relatives of HLHS patients.

Researchers recommend further studies to pinpoint specific genes responsible for the condition. Finding the genetic basis of HLHS could have significant implications for treating children with the disease, said D. Woodrow Benson, M.D., Ph.D., director of Cardiovascular Genetics at Cincinnati Children's and the study's senior author. This includes identifying possible interventions during fetal life (such as catheter-based procedures), the most appropriate postoperative drug therapies for individual children and determining the potential risks for failure of the right ventricle.

“By using family based linkage analysis, where specific genetic traits are mapped, it should be possible to identify the genes that cause the disease,” Dr. Benson said. “Once we know what genes are involved we can study how the disease developments, which may lead to new treatment approaches.”

Earlier studies in animals indicate HLHS may develop because of embryonic alterations in blood flow, such as a premature narrowing of the aortic valve and foramen ovale (which in the fetal heart allows blood to enter the left atrium from the right). Other studies have pointed to the role of certain genes (TBX5 and IRX1) in the formation of defective heart chambers with distinct shapes, functionality and molecular structure. Based on analysis of how these genes function, scientists hypothesize that HLHS may result from a primary defect in the growth of muscle tissue during the heart's development.

“Currently there are no experimental models to clarify the relative contributions of these two hypotheses to the development of HLHS,” Dr. Hinton said. “An important step forward in this research will be to understand the degree to which these hypothetical causes actually contribute to the condition.”

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Comments
  1. jessica jessica United States says:

    Hello my name is Jessica and I was wondering if there was any way for me to know if fell pregnant again would my next child have hypoplastic left heart syndrome too?

    • marie marie United States says:

      My first child had hlhs and passed just under 6 months old so i understand your concern. I have had 2 children since then and both are completely healthy and now adults. If you decide to get pregnant make sure your doctor tests for hlhs during your ultrasounds. good luck

    • Dawn marie Dawn marie United States says:

      I had 3 more healthy children after my hlhs baby.  I now have level 3 ultrasounds from a perinatolgist(hope I spelled that right).  They are trained to look specificly for that disorder.  They most likely would do 2 ultrasounds where they will compare the growth of all the heart chambers.  good luck.

    • Rebecca Rasmussen Rebecca Rasmussen United States says:

      My oldest son was born with HLHS in 1996.  He survived the surgeries and will he turning 16 this month.  I went on to have 4 more pregnancies.  Two of them ended in miscarriage of unknown reasons before the 3rd month.  The two that were successful required indepth ultrasounds of the heart just to make sure all the pieces were there.  For every pregnancy after my HLHS baby I was worried that the ultrasound wasn't right.  But I was reassured that everything was the way it was supposed to be.  My best advice is to ask lots of questions. Remember that your health care team is composed of trained professionals that can answer any question you have.  Because of my experiences with HLHS I went back to school to become a cardiac sonographer.

      GOOD LUCK!!!!!!!!  My prayers are with you.

    • Connie Connie United States says:

      Hi Jessica, I have also had 2 more children since the death of my first son as a result of HPLS and my children are of teen age and healthy!

    • Rachel Rachel Canada says:

      I just want to say that while the risk is low, it is still there. My mother had two children in a row in the early 80s with HPLS.

  2. Joanne Joanne United Kingdom says:

    hi my grandson was born with HLHS unknownn to us he looked perfect wen born and only due to havin low blood sugar he was kept in overnite were he suffered heart failure and was revived and taken to leeds hospital were we were told they couldnt do owt for him he died 31hours old i would like to know why every pregnant women is not given this scan as it was my daughters first baby my first grandchild and we would not want anyone else to suffer like we have does anyone know why this scan is not offered

  3. Crystal Crystal United States says:

    Jessica i understand your concern i had a baby in 2004 that was born with HLHS she died 4 months later. Its been 8 years i havent had another child due to fear. I have seen everyone comments i hope one day i can gain the strength to try again.

    • Margaret Margaret Australia says:

      Crystal  how hard it must have been for you and your partner to lose your precious. daughter. My grandchild  William is now 5 and also has HLHS . He is about to have his 3rd operation . I can understand  your fear to have another child but the world needs special parents like you and your partner to love a child born to them or to adopt a child  and protect and love them . I hope you are able to overcome  your fear .

    • Melanie Melanie United States says:

      Crystal, if you dont mind me asking, did your daughter have any of the 3 surgeries that go along with HLHS??

  4. Donna Donna United States says:

    We had a similar situation; my granddaughter was born with HLHS, which we also didn't know, also only because of low blood sugar taken to NICU and found; taken to UAB kept on prostaglandin and listed for heart transplant 1A, where still waiting but keeps getting sick with fevers. mom was given ultrasounds if that's what's meant by scans but has to be a specially trained person, is what I've been given to understand; the ones who did I don't think were but they just keep saying everything was fine on them but no way

  5. joanne joanne United Kingdom says:

    yes ultrasounds is scan i hope ur granddaughter gets her transplant and all goes well my daughter had 8 scans in all and every one she was told everthing is fine baby just stopped puttin weight on at 37 weeks so she got induced at 38 weeks but told all was ok but that was wrong good luck to u all and i really hope to hear good news that ur granddaughter is doin well.

  6. felecia felecia United States says:

    Hi my name is felecia and I have a 1 year old son that has hypoplastic left heart syndrome his daddy has a brother that had children that died and they had hypoplastic left heart syndrome. I'm pretty sure that it is genetic but idk.

  7. Cindy Cindy United States says:

    My grandson was born on Oct. 9 2012, so this is still pretty fresh on my mind.  Tyler looked perfect. He weighed in at 7.9 and was 20 inches long.  He looked like a healthy baby. At first they used oxygen on him then his blood gases were getting lower.  They were going to transfer him to a nearby hospital to a neonatal unit but he wasnt stable enough to make the 30 minute trip, so they came to us.  They had asked for a heart surgeon from the Childrens Hospital to come and she was in the air when baby Tyler passed away.  None of the pediatricians around here knew what to do, they had never had a case like this.  Tyler was 26 1/2 hours old when God called him home.  The only way we knew what had happened was through an autopsy.  My daughter plans on having another baby, but this time we know what to look for.  God bless all the families that have went through this ordeal.

  8. Shari Shari United States says:

    My son has HLHS, we have two daughters, one older and one younger who are both heart healthy. We had no idea before he was born about  his defect and almost lost him at 6 days old.

    He is an amazing young man who will finish college this semester.(ahead of schedule Smile )

  9. Linda Black Linda Black United States says:

    Luckily we live in an area where a top surgeon,Dr.Norwood,who invented the Norwood procedure for HLHS babies,was practicing. Childrens Hospital of Phila.I had an ultrasound during my 8th month of pregnancy.It showed that the head size was small or the abdomen was to large.We were sent to Pennsylvania Hospital Phila for a stage 2 ultasound which magnified everything.So it was found during my pregnancy.
    My labor was induced 3 weeks early,during a high risk delivery @ PA Hosp.And a few hours later Joey was tranferred to CHOP.He looked perfectly normal.I was told what happens is a few days after the babies are born the valve from the heart to the lung opens up,and if you are not aware of this condition ahead of time,the baby goes home, seems normal and becomes a"Blue Baby".
    Also during my labor I was given "options".Do nothing and the baby will pass naturally,heart transplant and the baby will have to wait for a heart to become available,or the "Norwood Procedure" which is a reconstruction of the heart with 3 separate surgeries(Joey also had a 4th called Post Fontan).
    I believe I made the right choice,if you go with the reconstruction,you still have the option of transplant later.Do nothing was not an option for me!
    Today Joey is doing Great!He was called" the kid with half a heart" in school,but he has the biggest heart of anyone I know!!
    Please comment!We would love to help anyone with concerns or doubts.Not all situations are the same,since there are different variations of HLHS. But we are here for a hug or shoulder to cry on!
    Thank you for reading!!

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
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