Genetics and Biomarkers in Congenital Heart Disease SSA Conference, November 9, 2010 . Everett, MD te Professor, Pediatric Cardiology . Taussig Children’s Congenital Heart Center
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Genetics and Biomarkers in Congenital Heart Disease
SSA Conference, November 9, 2010
Allen D. Everett, MDAssociate Professor, Pediatric CardiologyHelen B. Taussig Children’s Congenital Heart Center
Translating Congenital Heart Disease for the Non-Cardiologist
• This is a difficult task but I hope to better than this translation:
Genetics of Congenital Heart Disease
Genetics of Congenital Heart Disease
• Syndromic-Congenital heart disease associated with other defects such as brain, liver, etc. Uncommon, and tend to be single gene defects– Noonan’s (CHD, hematologic, neurologic) PTPN11– Alagille’s (CHD, liver disease) JAG1– Holt-Oram (CHD, skeletal defects) TBX5
Genetics of Congenital Heart Disease
• Non-syndromic-Congenital heart disease alone. Sporadic and common.– Incidence of gene mutations is low. In Hypoplastic
left heart syndrome, the incidence of mutations in NKX2.5, NOTCH1, HAND1 and GJA1 is 2%.
• Therefore occurrence is related to multifactoral inheritance of a multitude of susceptibility genes (unknown) with low penetrance mutations (being discovered) superimposed on unfavorable environmental conditions (unknown).
April 18, 2023 5
• Chromosomal deletions– 22q11: Tetralogy of Fallot, Interrupted
aortic arch and Tricuspid atresia.– Other less common are 9q34, 1q21.1,
16p11.2 and 17p11.2.– The use of genomic array technologies for
routine genetic screening is identifying an increasing number of chromosome microdeletions in children with CHD.
April 18, 2023 6
Genetics of Congenital Heart Disease
April 18, 2023 7
Genetics of Congenital Heart Disease
MW Wessels and PJ Willems. Clin. Genetics, 2010 78:103
Biomarkers in Congenital Heart Disease
• Biomarker (HUPO): Used to indicate or measure a biological process (for instance, levels of a specific protein in blood or spinal fluid, genetic mutations, or brain abnormalities observed in a PET scan or other imaging test). Detecting biomarkers specific to a disease can aid in the identification, diagnosis, and treatment of affected individuals and people who may be at risk but do not yet exhibit symptoms.
April 18, 2023 8
Biomarkers in Congenital Heart Disease
• Classic example is measurement of specific heart muscle proteins (troponin I) released into the circulation after a myocardial infarction.
• The heart also secretes hormones into the circulation when the workload of the heart is excessive. – Brain naturetic peptide (BNP)
April 18, 2023 9
Biomarkers in Congenital Heart Disease
• BNP – Shown to be a significant diagnostic measure of
heart failure in adults– In patients with pulmonary hypertension, a
significant predictor of sudden death– In children with CHD a potential indicator of poor
heart function and recovery after heart surgery– In the non-surgical setting the levels are so high in
children with CHD that they have little value.– May be useful in detecting transplant rejection.
April 18, 2023 10
Biomarkers in Congenital Heart Disease• Brain Injury Biomarkers
– 36-60% of neonates having surgery for CHD will have evidence of new brain injury on MRI
– Peri-operative brain injury is the most significant morbidity of CHD repair. The average Psychomotor Development Index score after CHD repair is 85, with normal 100.
– Identification of circulating brain specific proteins released with injury (similar to what happens with a myocardial infarction) will help improve and standardize perioperative care to reduce brain injury.
April 18, 2023 11
Translating Congenital Heart Disease for the Non-Cardiologist
• I hope my translation came out better than this:
Related Documents
