Cureus. 2026 Jul 6;18(7):e112187. doi: 10.7759/cureus.112187. eCollection 2026 Jul.
ABSTRACT
Williams syndrome (WS) is a rare microdeletion disorder affecting chromosome 7q11.23, including the ELN gene, which encodes elastin. Haploinsufficiency of ELN leads to vascular abnormalities, such as supravalvular aortic stenosis (SVAS), pulmonary stenosis, and coronary artery disease. SVAS can also occur in isolation due to heterozygous loss-of-function variants in ELN, independent of the broader WS deletion. We present a case of a term neonate with a Grade 4/6 systolic ejection murmur who underwent echocardiography, revealing severe supravalvular pulmonary stenosis, branch pulmonary artery stenosis, and mild SVAS. Due to these WS-like features, a chromosomal microarray was performed, which ruled out WS. Cardiac catheterization for pulmonary artery balloon angioplasty was complicated by ventricular fibrillation, requiring resuscitation. Angiography identified coronary artery stenosis. Intraoperative cardiac instability raised concerns for an ELN-related vasculopathy. Whole-exome sequencing (WES) revealed an ELN frameshift mutation in exon 6. This case describes a neonate with a WS-like cardiovascular phenotype but no WS-associated deletion, instead harboring a heterozygous pathogenic ELN loss-of-function variant consistent with isolated SVAS, thereby challenging genotype-phenotype correlations.
PMID:42564353 | PMC:PMC13443265 | DOI:10.7759/cureus.112187