Pediatric Cardio-Genetics PDF

Pediatric Cardio-Genetics Review • Genotype: the total genetic information of an organism • Phenotype: the physical manifestation of the genetic information • Homozygous: having two identical alleles of a particular gene • Heterozygous: two different alleles of a particular gene or genes • Hemizygou...

Pediatric Cardio-Genetics Review • Genotype: the total genetic information of an organism • Phenotype: the physical manifestation of the genetic information • Homozygous: having two identical alleles of a particular gene • Heterozygous: two different alleles of a particular gene or genes • Hemizygous: having only a single copy of a gene instead of two • Gene: a functional unit of the genome that contains the genetic information for one or more gene products • Allele: one of two or more variants of a gene • Polymorphism: a genetic variant where the rarer allele in a population occurs with a frequency of at least 1 % • SNP (single nucleotide polymorphism): a polymorphism where alleles vary at one base • Mutation: the occurrence of a change in the genomic sequence and the result of the change (usually disease related) Types of Mutations • Aneuploidy: Abnormal # of chromosomes (missing or extra) • Deletions • Duplications • Translocation • Gene Mutations o Gain vs. Loss o Missense o Nonsense o Frameshift Embryology of Heart Development • First functional organ to develop from embryonic mesoderm germ layer o Differentiates post gastrulation into mesothelium, endothelium, myocardium § Mesotheliumà forms outer layer of heart § Endothelium à forms lymph, blood vessels, endocardium o Begins pumping blood at day 21 or 22 (3wks post fertilization) Parts of the Primitive Heart • Truncus arteriosus gives rise to ascending Ao and pulmonary trunk • Bulbus cordis develop into the RV • Primitive ventricle develops into the LV • Primitive atrium becomes the anterior portions of both the RA, LA, and the two auricles • Sinus venosus develops into the posterior portion of the RA, the SA node, and the coronary sinus Congenital Heart Defect • VSD (ventricular septal defect; most common) • Risks for CHD: o Uncontrolled diabetes (3x risk increase) o Infection (rubella) o Family hx/genetics o Smoking o Diet o Alcohol o Illicit drug use o Some medications: § Dilantin § Thalidomide § ACE Inhibitors § Lithium § Isotretinoin (Retinoid) Causes of CHD: • Chromosomal o Aneuploidy o Trisomy (down syndrome) o Turners syndrome • Deletions o DiGeorge Syndrome o Williams Syndrome • Single Gene Disorder o Marfan syndrome Turners Syndrome • Aneuploidy: missing one X chromosome • Affects female o Short stature o Webbed neck (30%) o Abnormal carrying angle o Lymphedema at birth o Cardiac abnormalities o Loss of ovarian function common o No puberty unless on Hormone therapy o Extra folds of skin around neck • Cardiac Abnormalities: o Bicuspid aortic valve (30%) o Cortication of aorta (10%) • Dental Implications: o High arch palate o Crowding o Malocclusion Trisomy 21 Down Syndrome • 3 copies of chromosome 21 • 1 in 700 live births (quite common) • Risk of down syndrome increases w mother’s age (starts 30+, jumps dramatically by 40+) • 50% born with cardiac abnormalities o AV septal defect (endocardial cushion defect) o VSD o ASD Marfans Syndrome • Autosomal dominant • No gender preference • Low levels of FBN1 gene (fibrillin: a CT protein) on chromosome 15 • Symptoms: o Ectopic lentils (abnormal lens position) o Tall stature o long arms o Arachnodactyly (spider fingers) o Joint hypermobility • Cardiac o MV prolapse o Aortic regurgitation o Aortic root bulge Aneurysm o Aortic Dissection (tear) Williams Syndrome • 7q11.23 deletion of ELN (elastin) gene • Learning disabilities • Cocktail personality: talkative • Periorbital fullness • Heavy sagging cheeks • Short nose • Poor bow of lip • Supravalvular aortic stenosis (50-75%) • Tetralogy of Fallot (TOF) o Related to 22q11 syndromes (DiGeorge and FAS) o 4 components: § Pulmonary infundibular stenosis (most important prognostically) § RV hypertrophy (RVH): ‘Boot shaped’ heart due to upturned cardiac apex § Overriding Aorta § VSD DiGeorge Syndrome (CATCH 22) • Most common CHD • Microdeletion of chromosome 22q11.2 • Symptoms can vary o (C) Cleft palate o (A) Abnormal facial features o (T) Thymic hypoplasia o (C) Cardiac defects: Tetralogy of Fallot is most common o (H) Hypocalcemia Fetal Alcohol Syndrome (FAS) • 22q11 region (not deletion) • Alcohol during pregnancy • Symptoms vary: o Brain damage (learning disability ADHD) o Growth problems (deformities) o Cardio: § VSD § PDA § ASD § TOF • Complications of FAS: o Mental health problems o Problems staying in or completing school o Trouble with the law o Inability to live independently o Inappropriate sexual behaviors o Early death by accident, homicide, or suicide Questions Which primitive area of the heart will give rise to the right ventricle? a. truncus arteriosus. b. bulbus cordis c. primitive ventricle d. sinus venosus Which of the following does NOT include four components of Tetralogy of Fallot? a. Pulmonary infundibular stenosis b. Boot-shaped heart c. Coarctation aorta d. VSD e. Overriding aorta