PM1042: Sudden Cardiac Arrest During a Sedated Cardiac Magnetic Resonance Study in a Nonsyndromic Child with Evolving Supravalvar Aortic Stenosis Due to Familial ELN Gene Mutation

Introduction: Supravalvar aortic stenosis (SVAS) is commonly associated with Williams Syndrome (WS). Sporadic or familial forms of SVAS can also occur in the absence of WS, sometimes with associated mutations in the elastin (ELN) gene. Risk of sudden cardiac arrest and death (SCAD) in patients with WS and SVAS is well described, but far less is known about nonsyndromic children with more isolated SVAS.

Case Description: We report a case of a previously healthy 2-year-old boy initially referred for murmur evaluation, who subsequently developed relatively mild but evolving SVAS. The patient had no syndromic features and prenatal genetic testing was negative, but given the cardiac manifestations and strong family history of SVAS (though no WS), targeted genetic testing was performed which identified an ELN gene mutation in the proband (patient’s father) and other affected relatives. During follow up testing the child developed unexpected sudden cardiac arrest and death during a sedated cardiac magnetic resonance imaging study.

Discussion: SVAS (and other arterial stenoses) can occur outside of WS particularly when in the context of an ELN mutation, and can collectively be termed Elastin Arteriopathy (EA). Risk for SCAD in nonsyndromic patients with EA is poorly described, and likely underrecognized. Cardiac manifestations and higher risk for SCAD may be similar to patients with WS, especially during anesthesia or the periprocedural period, but may be difficult to predict and can occur even in the absence of severe disease, as our case demonstrated. To our knowledge, this is the first reported case of SCAD in a non-WS child with SVAS during a non-invasive study. We use this case to raise awareness of the risk of cardiac events in children with EA. Sedated procedures should be avoided in infants and toddlers with EA unless absolutely necessary due to the likely increased but sometimes unpredictable risk of SCAD. Traditional genetic testing such as karyotype or chromosomal microarray, while commonly utilized in cases of congenital heart disease, or not sensitive enough to detect isolated gene mutations, such as ELN. More recently available targeted gene panels should thus be utilized, and promise to improve identification of ELN mutations in patients with SVAS.

Conclusion: Patients with SVAS may be at increased risk for SCAD, even in the absence of WS. Targeted genetic testing, especially for ELN gene mutations, which can carry significant clinical and genetic ramifications, should be pursued in all patients with SVAS even when phenotypic concerns for WS are lacking. Better identification and understanding of EA in children may help optimize counseling, cascade family genetic testing, coordination of periprocedural care, and avoidance of adverse outcomes in these fragile patients.