What conditions can cause pectus excavatum?

Conditions That Can Cause Pectus Excavatum

Pectus excavatum is most commonly associated with connective tissue disorders, particularly Marfan syndrome and related genetic conditions, but can also occur as an isolated finding or as part of other syndromes. The etiology primarily involves abnormalities in costal cartilage structure and function 1.

Genetic and Syndromic Causes

Marfan Syndrome and Related Disorders

• Marfan syndrome (FBN1 gene mutation) - Pectus excavatum is a common skeletal manifestation alongside aortic root aneurysm, mitral valve prolapse, long bone overgrowth, scoliosis, and ectopia lentis 2
• Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 mutations) - Features thoracic aortic aneurysms, arterial tortuosity, and skeletal features including pectus deformities 2
• MASS phenotype - Mitral valve prolapse, aortic enlargement (not progressive), skin and skeletal features including pectus excavatum 2, 3
• Ehlers-Danlos syndrome - Particularly the vascular type (COL3A1 mutation) which can present with pectus deformities 2

Other Genetic Conditions

• Familial pectus excavatum - Can occur as an autosomal dominant trait in some families 2
• Bicuspid aortic valve sequence - Associated with thoracic cage deformities including pectus excavatum 2
• Familial tall stature - Some families with FBN1 mutations show pectus excavatum and tall stature without cardiovascular problems 2
• Smooth muscle dysfunction syndrome (ACTA2 mutation) - Can present with thoracic aortic aneurysm and pectus deformities 2

Non-Syndromic Causes

Isolated Pectus Excavatum

• Idiopathic/sporadic cases - Most common presentation, occurring in approximately 1 in 300-1000 live births with a male predominance (5:1 ratio) 4
• Familial non-syndromic cases - Can occur in families without other features of connective tissue disorders 2

Associated Conditions

• Scoliosis - Often co-occurs with pectus excavatum 2, 5
• Mitral valve prolapse - Frequently associated with pectus excavatum even in the absence of Marfan syndrome 2, 3
• Asthma - Higher prevalence (8.8%) in patients with pectus excavatum 5

Pathophysiological Considerations

The exact mechanism leading to pectus excavatum remains unclear, but current evidence suggests:

1. Abnormal costal cartilage growth - Overgrowth or structural abnormalities of costal cartilage appear to be the primary defect 1
2. Connective tissue abnormalities - Particularly in cases associated with Marfan syndrome and other connective tissue disorders 6, 3
3. Biomechanical factors - Altered chest wall mechanics during development 1

Clinical Implications

• Patients with pectus excavatum should be evaluated for associated connective tissue disorders, particularly when other features are present 2, 7
• Cardiovascular assessment is essential, as many associated conditions have cardiac manifestations 7
• Surgical correction of pectus excavatum should be delayed if aortic root dilation is present and approaching surgical thresholds (≥4.5 cm), as aortic root surgery takes precedence 7
• Recurrence after surgical repair is more common in patients with Marfan syndrome (approximately 39%) compared to those with isolated pectus excavatum 6

Screening Recommendations

For patients presenting with pectus excavatum, consider screening for:

1. Cardiovascular abnormalities - Echocardiogram to assess for mitral valve prolapse, aortic root dilation
2. Ocular manifestations - Dilated eye examination to evaluate for ectopia lentis
3. Skeletal features - Evaluation for scoliosis, joint hypermobility, long bone overgrowth
4. Family history - Assessment for similar chest wall deformities or features of connective tissue disorders

While approximately 56% of patients with pectus excavatum have no associated conditions 5, the presence of additional features should prompt consideration of underlying genetic or syndromic causes.