Isolated aortic root dilatation – Expanding the cardiac phenotype of 22q11 deletion syndrome

Dear Sir,

Aortopathies are conditions associated with dilatation of the aortic root, and these represent an increased risk for aortic dissection and potentially sudden death. The aortopathies are commonly attributed to connective tissue disorders such as Marfan Syndrome and Loeys–Dietz syndrome. Aortic root dilatation is also a reported phenotype in children with conotruncal defects, as well as those with transposition of the great arteries. The presence of a 22q11 deletion has been shown to be an independent risk factor for aortic root dilatation in children with Tetralogy of Fallot.[1] However, isolated aortic root dilatation in the absence of conotruncal abnormalities is not part of the commonly reported phenotype of 22q11 deletion. We report two children with aortic root dilatation and 22q11 deletion syndrome.

A 2-year-old girl was referred to us for evaluation of suboptimal weight gain. The child exhibited some facial features suggestive of DiGeorge syndrome. Echocardiogram showed a moderate-sized atrial septal defect. The aortic valve was trileaflet, and the aortic root was dilated, measuring 18.6 mm (z-score: +2.7) [Figure 1a and Video 1]. There was a crossed origin of the pulmonary arteries, although both branches were unobstructed [Video 2]. Subsequently, a 9-year-old girl was referred to us for episodic palpitation and lightheadedness. Her clinical examination was normal except for arachnodactyly. Echocardiogram showed a structurally normal heart with a trileaflet aortic valve and aortic root dilatation [Figure 1b and Video 3]. The root measured 27.4 mm (z-score: +2.78). The ophthalmological evaluation was negative in both children.

Figure 1.

(a) Echocardiogram image in the para-sternal long axis view of patient 1 demonstrating a dilated aortic root measuring 18.6 mm. (b) Echocardiogram image in the para-sternal long axis view of patient 2 demonstrating a dilated aortic root measuring 27.4 mm

Both children underwent genetic testing because of a suspected aortopathy. No potentially causative variant was identified in the aortopathy genes. However, a deletion of the 22q11 region was identified in both children on copy number variant analysis (a 2.91 Mbp deletion (chr 22: 18653509-21563411) in the first child and a 0.364 Mbp partial deletion (chr 22:19711356-19748823) in the second child, which included the TBX1 gene).

When a pediatric cardiologist assesses a child with 22q11 deletion syndrome, isolated aortic root dilatation is not a finding that comes to mind. However, this was reported in 9% of children with DiGeorge syndrome by John et al.[2] The average age of the cohort was above 6 years, and 5 of the 8 children in the cohort had a previous echocardiogram, in which a normal aortic root dimension was reported, suggesting that aortic root dilatation could progress over time. However, in a larger cohort of children with isolated aortic root dilatation and 22q11 deletion from the same institution, de Rinaldis et al. reported that the aortic root dilatation normalized in approximately half the children but progressed in the others.[3] Among the older children with initial progression in aortic root dilatation, the z-scores tend to decrease. Male sex was the only identified risk factor for aortic root dilatation. No dissection was reported in this series. Despite the prospective profiling of a large cohort, no clinical implications were identified in this study.[3] The degree of aortic root dilatation was mild and below the accepted criteria for an intervention in both our cases. The exact genetic basis of aortic root dilatation in patients with 22q11 deletion is not yet known. However, the TBX1 gene is the most likely causative factor given its importance in the formation of the conotruncal region.[4]

Isolated aortic root dilatation may be part of the phenotype of 22q11 deletion. However, its clinical significance is unclear; therefore, it may be reasonable to keep children with 22q11 deletion and structurally normal hearts on regular cardiac follow-up every few years until we better understand the phenotype of aortic root dilatation.

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Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.