Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex

Pediatrics. 2006 Oct;118(4):e1146-51. doi: 10.1542/peds.2006-0504. Epub 2006 Aug 28.


Objective: Tuberous sclerosis complex is an autosomal dominant disorder in which hamartomas occur in several organs. Cardiac rhabdomyomas, the most common heart tumors of childhood, are well known to be associated with tuberous sclerosis complex. Our aim for this study was to characterize the incidence, progression, and clinical consequences of tuberous sclerosis complex-associated rhabdomyomas in a large cohort of patients with TSC1 and TSC2 genotypes.

Patients and methods: Patients (154) with tuberous sclerosis complex were evaluated, including clinical assessment, electrocardiography, and echocardiography. Mutations in TSC1 or TSC2 genes were identified in 127 patients.

Results: Cardiac rhabdomyomas were found in 74 (48%) patients. Tumors were most frequent in children younger than 2 years (65%). Tumor regression or disappearance was observed in 37 (68%) of 55 children. However, in 6 (3.9%) of them (aged 10-15 years), cardiac rhabdomyomas were noted to either grow (3 cases) or appear de novo (3 cases), such that the frequency of cardiac rhabdomyomas in adolescents was 6 (54%) of 11. Most (61%) tumors were clinically silent. Clinical manifestations included heart failure (5.4%), arrhythmias (23%), and murmurs (14.9%). One child died as a result of cardiac insufficiency. Cardiac rhabdomyomas were more frequent in the TSC2 (54%) than TSC1 (20%) groups.

Conclusions: Cardiac rhabdomyomas are seen in the majority of young children with tuberous sclerosis complex. Most produce no clinical consequences and will spontaneously regress. However, during puberty, cardiac rhabdomyomas may enlarge or appear de novo; thus, attention should be paid to potential clinical signs and monitoring by echocardiography should be performed. Cardiac rhabdomyomas were observed more often in the TSC2 group.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Genotype
  • Hamartoma / complications
  • Hamartoma / genetics*
  • Hamartoma / pathology*
  • Heart Diseases / etiology
  • Heart Neoplasms / complications
  • Heart Neoplasms / genetics*
  • Heart Neoplasms / pathology*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Prognosis
  • Puberty
  • Tuberous Sclerosis / genetics*
  • Tuberous Sclerosis / pathology*
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*


  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins