Cardiovascular
for pediatric cardiomyopathy and congenital heart disease with exome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Early cardiomyopathy
- Unexplained arrhythmias
- Congenital heart defects
- Syncope
- Early heart failure
- Hypertrophic/dilated/restrictive cardiomyopathy
- Arrhythmogenic RV cardiomyopathy
- Long QT
- Brugada
- Thoracic aortic aneurysm syndromes
- Complex CHD
- Murmurs with structural disease
- Irregular rhythm
- Tachy/bradycardia
- Abnormal pulses
- Signs of heart failure (hepatomegaly, edema)
- Marfanoid habitus
- Palpitations
- Chest pain with exertion
- Syncope or presyncope
- Dyspnea
- Dizziness
- Marked exercise intolerance
- Fatigue out of proportion to activity
- Elevated BNP or NT-proBNP
- Elevated troponin without ischemia
- Lactate elevation with cardiomyopathy
- Abnormal carnitine profile
- Metabolic acidosis in heart failure
- Echo showing hypertrophic/dilated cardiomyopathy
- Complex CHD
- Aortic root dilation or aneurysm
- Cardiac MRI with fibrosis
- Anomalous coronary arteries
- Conduction abnormalities on EKG
- ECG with long QT/Brugada/WPW patterns
- Holter showing arrhythmias/pauses/blocks
- Stress test abnormal without ischemia
- Echo serially showing progressive cardiomyopathy
- Childhood use of antiarrhythmics
- Beta-blockers for long QT
- ACE inhibitors or diuretics in early life
- Poor response to standard CHF meds
- Cardiovascular collapse with anesthesia or certain meds in absence of structural disease
- Arrhythmias triggered by common meds
- Early cardiac surgeries for complex CHD (AV canal, TOF, TGA, truncus)
- Pacemaker or ICD placement in childhood
- Repeated catheter-based interventions
- Cardiac rehab or exercise restriction guidance in young patients with cardiomyopathy or arrhythmia risk
- Pacemaker
- ICD
- Loop recorder in children
- Cardiac monitors used long-term
- Pediatric cardiology following for CHD/cardiomyopathy/arrhythmias
- Syncope or inherited arrhythmia clinics
- Cardio-genetics referral
- Sudden cardiac death under 40
- Cardiomyopathy (HCM/DCM/RCM)
- Arrhythmias requiring pacemaker
- Aortic aneurysm/dissection
- Long QT
- Unexplained drownings or accidents
- No stimulant/drug exposure or extreme athletic training to explain arrhythmias or cardiomyopathy
- Healthy lifestyle but early cardiac disease
- Cyanosis
- Murmur
- Abnormal fetal echocardiogram
- Early tachy/bradycardia
- Poor perfusion
- Signs of critical CHD
- Need for prostaglandin or emergent cardiac intervention
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Cardiomyopathy + hearing loss
Arrhythmias + syncope + family history of sudden death
CHD + extracardiac anomalies
Aortic dilation + tall stature + lens issues
Screening Decision Pathway
When to consider genetic testing for cardiovascular presentations
graph TD
START["Patient Presents with\nCardiovascular Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Abnormal pulse oximetry CCHD screen"]
SCREEN --> RF2["Prolonged QT or arrhythmia on school or sports ECG"]
SCREEN --> RF3["Abnormal syncope screen responses"]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n32-67% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Abnormal pulse oximetry CCHD screen
- Prolonged QT or arrhythmia on school or sports ECG
- Abnormal syncope screen responses
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Cardiomyopathy or arrhythmias at young age without acquired cause
- CHD with extra-cardiac anomalies
- Aortic disease with syndromic features
- Strong family history of sudden death
Key Evidence
Published studies supporting genetic testing for cardiovascular conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Exome sequencing covers >98% of mutations identified on targ... | 2017 | Cohort | None | None | WES covers >98% of variants identified by targeted cardiac gene panels, supporti... |
| Diagnostic yield of retesting in inherited cardiac arrhythmi... | 2018 | Cohort | None | 20% | NGS retesting yielded 20% additional diagnoses in previously negative inherited ... |
| Exome sequencing in infantile heart failure: An approach to ... | 2019 | Cohort | None | 66.7% | Exome sequencing achieved 66.7% diagnostic yield in infantile heart failure, ide... |
| 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Ca... | 2021 | Cohort | 2183 | 25% | 25% diagnostic yield in 2183 rare disease families; monogenic disorders 35% vs c... |
| The Genetic Architecture of Pediatric Cardiomyopathy | 2022 | Cohort | None | 32% | 32% genetic cause identified in 528 children with cardiomyopathy; infants <1 yea... |
| Assessment of Combined Cardiomyopathy and Arrhythmia Genetic... | 2022 | Cohort | 4782 | 19.9% | Combined cardiomyopathy and arrhythmia genetic testing yielded 19.9% positive ra... |
| Diagnostic Yield of Exome Sequencing in Pediatric Cardiomyop... | 2024 | Cohort | None | 39.6% | 39.6% diagnostic yield in pediatric cardiomyopathy, 61% of diagnoses missed by c... |
| Pediatric Cardiovascular Genomics: Diagnostic Yield of Next-... | 2024 | Cohort | None | None | NGS approaches for pediatric cardiovascular disease demonstrate high diagnostic ... |
Updated: 2026-02-24
Curated by: human
Status: human reviewed