Cardiovascular Syndromes: Genetics and Inheritance

Gene/chromosome: Usually sporadic, heterogeneous; Inheritance: Multifactorial, sometimes 22q11.2 deletion; Tetrad: VSD, RV outflow obstruction, overriding aorta, RV hypertrophy; Associated: Cyanotic CHD; Investigation: Echocardiography, boot-shaped heart on X-ray

Gene/chromosome: No single gene; Inheritance: Acquired complication of congenital shunt; Triad: Pulmonary hypertension, shunt reversal, cyanosis; Associated: VSD, ASD, PDA; Investigation: Echocardiography, cardiac catheterization

Gene/chromosome: No single gene; Inheritance: Acquired combination; Triad: ASD, mitral stenosis, pulmonary hypertension; Associated: Rheumatic mitral stenosis; Investigation: Echocardiography

Gene/chromosome: TBX5, chromosome 12; Inheritance: Autosomal dominant; Triad: Radial ray defects, ASD, conduction abnormalities; Associated: ASD, VSD; Investigation: Echocardiography, ECG, TBX5 testing

Gene/chromosome: PTPN11 and RAS-MAPK pathway genes; Inheritance: Autosomal dominant; Triad: Short stature, webbed neck, hypertelorism; Associated: Pulmonary stenosis, hypertrophic cardiomyopathy; Investigation: Echocardiography, molecular panel

Gene/chromosome: FBN1, chromosome 15; Inheritance: Autosomal dominant; Triad: Arachnodactyly, aortic root dilatation, ectopia lentis; Associated: Aortic aneurysm/dissection, mitral valve prolapse; Investigation: Echocardiography, slit-lamp examination, FBN1 testing

Gene/chromosome: COL5A1/COL5A2 classical type; COL3A1 vascular type; Inheritance: Usually autosomal dominant; Triad: Hyperextensible skin, joint hypermobility, tissue fragility; Associated: Vascular type causes arterial rupture; Investigation: Clinical criteria, genetic testing

Gene/chromosome: 7q11.23 deletion, ELN; Inheritance: Usually de novo microdeletion; Triad: Elfin facies, hypercalcemia, sociable personality; Associated: Supravalvular aortic stenosis; Investigation: Echocardiography, FISH/microarray

Gene/chromosome: PTPN11, chromosome 12; Inheritance: Autosomal dominant; Triad: Lentigines, ECG abnormalities, ocular hypertelorism; Associated: Pulmonary stenosis, hypertrophic cardiomyopathy; Investigation: ECG, echocardiography, PTPN11 testing

Gene/chromosome: KCNQ1 or KCNE1; Inheritance: Autosomal recessive; Triad: Long QT, congenital sensorineural deafness, syncope; Associated: Torsades de pointes, sudden cardiac death; Investigation: ECG, audiometry, genetic testing

Gene/chromosome: KCNQ1, KCNH2 and other genes; Inheritance: Autosomal dominant; Triad: Long QT, syncope, ventricular arrhythmias; Associated: Torsades de pointes, sudden cardiac death; Investigation: ECG, genetic testing

Gene/chromosome: SCN5A in some cases; Inheritance: Usually autosomal dominant; Triad: Coved ST elevation V1–V3, syncope, ventricular arrhythmias; Associated: Sudden cardiac death; Investigation: ECG, sodium-channel blocker challenge when indicated

Gene/chromosome: Usually sporadic; PRKAG2 in familial cases; Inheritance: Usually sporadic, occasionally autosomal dominant; Triad: Short PR, delta wave, widened QRS; Associated: AV reentrant tachycardia, atrial fibrillation; Investigation: ECG, electrophysiology study

Gene/chromosome: PRKAR1A, chromosome 17; Inheritance: Autosomal dominant; Triad: Cardiac myxoma, spotty pigmentation, endocrine tumors; Associated: Cardiac myxoma; Investigation: Echocardiography, PRKAR1A testing

Gene/chromosome: STK11, chromosome 19; Inheritance: Autosomal dominant; Triad: Mucocutaneous pigmentation, hamartomatous polyps, abdominal pain; Associated: GI, pancreatic, breast and gynecologic cancers; Investigation: Endoscopy, STK11 testing