The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis

Spine J. 2020 Jun;20(6):956-963. doi: 10.1016/j.spinee.2020.01.006. Epub 2020 Jan 18.


Background context: For over four decades, clinicians and researchers have suggested a relationship between congenital heart disease (CHD) and scoliosis, attributed to either the disease itself or to the long-term effects of cardiac surgery on the immature thoracic cage. However, no study has yet accounted for 22q11.2 deletion syndrome (22q11.2DS), the second most common cause of CHD after Down syndrome. 22q11.2DS has a scoliosis risk of 50%, but within 22q11.2DS a previous report found no significant association between scoliosis and CHD. We, therefore, hypothesized that scoliosis within a CHD cohort would be related to an underlying 22q11.2 deletion.

Purpose: To determine the prevalence of scoliosis in CHD patients with and without 22q11.2DS.

Study design/setting: Cross-sectional.

Patient sample: A well-characterized existing database of 315 adults with CHD (primarily tetralogy of Fallot), with (n=86) and without (n=229) 22q11.2DS, matched by sex and CHD severity, and excluding other known syndromic diagnoses. We compared the scoliosis prevalence of patients with 22q11.2DS and CHD patients to the prevalence of scoliosis in a cohort of adults with 22q11.2DS without CHD based on medical records.

Outcome measures: Presence of scoliosis (Cobb angle ≥10°).

Methods: We systematically determined the presence of scoliosis in all included patients using chest radiographs, blind to genetic diagnosis. Besides 22q11.2DS, we analyzed other suspected risk factors for scoliosis using a regression model: thoracotomy before the age of 12 years, severe CHD type and sex.

Results: The prevalence of scoliosis in adults with CHD and 22q11.2DS (n=46, 53.5%) was significantly greater than in those without 22q11.2DS (n=18, 7.9%, p<.0001). The presence of a 22q11.2 deletion (odds ratio [OR] 25.4, 95% confidence interval [95% CI] 11.2-57.4, p<.0001), a history of thoracotomy before the age of 12 years (OR 3.5, 95% CI 1.6-8.1, p=.0027) and most complex CHD class (OR 2.3, 95% CI 1.1-4.7, p=.0196), but not sex, were significant independent predictors of scoliosis. In the 22q11.2DS group, a right-sided aortic arch was associated with a left thoracic scoliotic curve (p=.036).

Conclusions: The prevalence of scoliosis in those with CHD but without a 22q11.2 deletion approximates that of the general population. However, in the CHD population with a 22q11.2 deletion, the prevalence of scoliosis approximates that of others with 22q11.2DS. The pediatric surgical approach and severity of CHD were weaker independent contributors as compared to the 22q11.2 deletion. The results support the importance of a genetic diagnosis of 22q11.2DS to the risk of developing scoliosis in individuals with CHD. The 22q11.2 deletion may represent a common etiopathogenetic pathway for both CHD and scoliosis, possibly involving early laterality mechanisms.

Keywords: 22q11.2 deletion syndrome; Chest radiograph; Congenital; Congenital heart disease; Copy number variant; DiGeorge syndrome; Musculoskeletal; Scoliosis; Spine; Thorax radiograph.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Cross-Sectional Studies
  • DiGeorge Syndrome* / complications
  • DiGeorge Syndrome* / epidemiology
  • DiGeorge Syndrome* / genetics
  • Female
  • Heart Defects, Congenital* / epidemiology
  • Heart Defects, Congenital* / genetics
  • Humans
  • Marfan Syndrome*
  • Scoliosis* / diagnostic imaging
  • Scoliosis* / epidemiology
  • Scoliosis* / genetics
  • United States
  • Young Adult