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A child under ten years of age with structural or functional cardiomyopathy on echocardiography: hypertrophic (HCM), dilated (DCM), restrictive (RCM), or left ventricular non-compaction (LVNC). Childhood cardiomyopathies are not a milder version of adult cardiomyopathy; the etiologic distribution is different, the inherited fraction is higher (roughly half of pediatric DCM and the majority of pediatric HCM are genetic), and the must-not-miss diagnoses are treatable inborn errors rather than coronary disease. The presenting story is usually heart failure, an incidental murmur, an abnormal screening echo in a family member, or a metabolic crisis with cardiac involvement.
Three questions structure the work-up:
- What morphology? HCM, DCM, RCM, or LVNC. Each has its own short list.
- Is it syndromic or extracardiac features present? A dysmorphic face, hypotonia, hepatomegaly, skeletal myopathy, or developmental delay says the heart is one organ in a larger disorder.
- What is the family history? Three generations, including unexplained sudden death, transplants, pacemakers, drownings, and "heart attacks" before age 50. Many parents are asymptomatic carriers.
Sarcomeric, syndromic, and metabolic causes overlap morphology categories, but each morphology has a characteristic short list.
Hypertrophic cardiomyopathy (HCM) in childhood
- Sarcomeric HCM: MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, ACTC1, TPM1. AD; the adult HCM genes also present in childhood, usually milder phenotypes than the syndromic and metabolic causes.
- RASopathies: Noonan syndrome (PTPN11, RAF1, SOS1) is the most common syndromic cause of HCM in childhood; Costello syndrome (HRAS) and cardio-facio-cutaneous (BRAF) also feature HCM. Look for short stature, pulmonary stenosis, characteristic facies.
- Pompe disease (GSD II): the must-not-miss. Profound hypotonia + HCM in an infant. Treatable with enzyme replacement therapy; outcomes depend on early start (ideally < 6 months). Send acid α-glucosidase activity on dried blood spot the same day.
- Danon disease (LAMP2, X-linked): HCM + skeletal myopathy + intellectual disability; Wolff-Parkinson-White preexcitation is a recognizable signature. Males severe, females milder later onset.
- Mitochondrial cardiomyopathy: lactic acidosis, multisystem features (Leigh, MELAS overlap).
- Friedreich ataxia: HCM appears before or alongside neurologic features in some patients.
Dilated cardiomyopathy (DCM) in childhood
- Sarcomeric DCM: titin (TTN, AD, usually adult onset but pediatric described), LMNA (DCM with conduction disease and atrial arrhythmias, AD), MYH7, ACTC1.
- X-linked muscular dystrophies: Duchenne and Becker (DMD). DCM is a leading cause of death in Duchenne by the third decade. Manifesting female carriers can present with isolated DCM before any skeletal weakness; always check the mother of a male proband.
- Mitochondrial DCM: lactic acidosis, encephalopathy.
- Metabolic / FAO defects: VLCAD and LCHAD/TFP cause DCM with hypoketotic hypoglycemia.
- Acquired: myocarditis, anthracycline toxicity, tachycardia-induced. Important to exclude before settling on genetic etiology.
Left ventricular non-compaction (LVNC)
- MYH7, ACTC1, TAZ. Barth syndrome (TAZ, X-linked) is the classic pediatric LVNC: LVNC + cyclic neutropenia + skeletal myopathy + 3-methylglutaconic aciduria + growth failure.
Restrictive cardiomyopathy (RCM)
- Rare in children. Sarcomeric variants (TNNT2, TNNI3, MYH7), iron overload (transfusion-dependent thalassemia, hereditary hemochromatosis in older patients), amyloid (rare in childhood). Often progresses rapidly to transplant.
- Infant with profound hypotonia + HCM → Pompe disease. Acid α-glucosidase today; ERT tomorrow.
- HCM + short stature + pulmonary stenosis + downslanting palpebral fissures → Noonan syndrome or other RASopathy.
- DCM + skeletal myopathy in a school-age boy → Duchenne muscular dystrophy. CK is the screening test.
- DCM in a young woman with conduction disease → LMNA.
- DCM in an otherwise well mother of a DMD-affected boy → manifesting carrier; counsel the family.
- LVNC + neutropenia + skeletal myopathy + 3-methylglutaconic aciduria → Barth syndrome.
- HCM + WPW preexcitation + skeletal myopathy → Danon disease.
- DCM + hypoketotic hypoglycemia after illness → fatty acid oxidation defect (VLCAD, LCHAD).
- Echocardiogram with strain imaging and 12-lead ECG: confirm morphology, look for WPW (Danon, Pompe), conduction disease (LMNA), QT abnormalities.
- Three-generation family history: cardiomyopathy, sudden death, transplant, pacemaker, drownings, unexplained early death.
- CK (Duchenne, Becker, manifesting carriers), lactate, ammonia, acylcarnitine profile (FAO defects, Barth), urine organic acids (3-MGA in Barth, methylmalonic and propionic in organic acidemias).
- Acid α-glucosidase activity (GAA) on dried blood spot if HCM in an infant: Pompe screen, fastest reflex available.
- Cardiomyopathy gene panel (or trio exome if extracardiac features). Choose the panel that matches the morphology; many commercial panels cover HCM, DCM, RCM, LVNC, and channelopathies together.
- Cardiac MRI in older children for fibrosis (late gadolinium enhancement) and to characterize LVNC.
- Cascade screening of first-degree relatives once a variant is identified: ECG + echo for all, genetic testing for the specific variant.
- Pompe disease is the diagnosis you do not want to miss in an infant with HCM and hypotonia. ERT works best when started before irreversible muscle injury; six months is the rough cutoff.
- Always check the mother of a Duchenne proband for DCM. Manifesting carriers exist and an asymptomatic DCM at age 35 can be the first family signal.
- HCM in a syndromic-looking child is RASopathy until proven otherwise. The face is the diagnostic test; the gene panel confirms.
- LVNC with neutropenia is Barth syndrome until proven otherwise; the urine organic acid screen (3-MGA) is the cheap fast confirmer.
- Cascade screening is the point of making the genetic diagnosis. Identifying an at-risk relative who is still asymptomatic is the win.