Description

Deformity of pulmonary valve, most commonly congenital, resulting in obstruction of right ventricular (RV) outflow

Epidemiology

Incidence

• Predominant age: congenital, present in newborns but often asymptomatic for years
• Predominant sex: female > male (1)
• African Americans (46.5%), Hispanics (33.1%), and Caucasians (20.4%) (1)

Prevalence

• 10% of all cases of congenital heart disease
• In association with other lesions, may be as high as 25–30% of congenital heart disease (1)

Etiology and Pathophysiology

• Pulmonary stenosis can occur at three levels: valvular, subvalvular, and supravalvular.
• <20% of cases of valvular stenosis are associated with a bicuspid valve.
• RV hypertrophy (RVH) tends to occur with pulmonary regurgitation.
• Pulmonary stenosis may also be associated with pulmonary artery dilation due to underlying connective tissue abnormality and flow through the stenotic pulmonary valve.
• Supravalvular stenosis is usually associated with congenital syndromes.
• Congenital etiologies cause an abnormal development of distal bulbus cordis secondary to:
  • Rubella embryopathy (most important etiology)
  • Isolated branch pulmonary artery stenosis (stenosis of a sling of the ductus arteriosus)
  • Congenital/genetic syndromes described below
• Acquired etiologies:
  • Stenosis of bioprosthetic valve
  • Rarely, rheumatic fever and carcinoid syndrome

Genetics

• Genetic causes are likely, with numerous familial and syndromic cases.
• Mutated genes vary depending on the syndrome of which the stenosis forms part. Some of the most important are:
  • PTPN11 gene in Noonan and LEOPARD syndromes
  • Elastin gene (ELN) in 7q.11.23 locus in Williams-Beuren syndrome
  • JAG1 gene in Alagille syndrome
  • Matrix Gla protein gene in Keutel syndrome
  • NF1 gene in neurofibromatosis

Risk Factors

• Family history
• Rubella infection in utero
• Valvular stenosis may cause outflow track narrowing due to RVH, leading to additional subvalvular stenosis.
• There is an increased risk of arrhythmia in patients with pulmonic stenosis. Only symptomatic arrhythmias require further evaluation.

General Prevention

Rubella vaccination (before conception) to avoid in utero transmission of rubella is the best way to prevent most cases.

Commonly Associated Conditions

• Tetralogy of Fallot
• Noonan and LEOPARD syndromes: dysplastic/supravalvular
• Neurofibromatosis
• Williams syndrome: supravalvular
• Alagille syndrome: peripheral
• Keutel syndrome: peripheral
• Ventricular septal defect and atrial septal defect (relative stenosis for the increased flow)