P2.030: A Novel ELN Mutation Mimicking Williams Syndrome Cardiovascular Phenotype

Introduction: Williams syndrome (WS) is a rare microdeletion disorder affecting chromosome 7q11.23, including the ELN gene, which encodes elastin. Loss of elastin leads to vascular abnormalities such as supravalvular aortic stenosis (SVAS), pulmonary stenosis, and coronary artery disease. This case describes a neonate with a WS-like cardiovascular phenotype but no WS-associated deletion, instead harboring a heterozygous pathogenic ELN mutation variant, challenging genotype-phenotype correlations.

Case Description: A term neonate with a grade 4/6 systolic murmur underwent echocardiography, revealing severe supravalvular pulmonary stenosis, branch pulmonary artery stenosis, and mild supravalvular aortic stenosis. Due to these WS-like features, a chromosomal microarray was performed, and it ruled out Williams syndrome. 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 elastin-related vasculopathy. Whole exome sequencing revealed an ELN frameshift mutation at exon 6.

Discussion: This case highlights a novel frameshift variant of ELN gene, which results in protein truncation or nonsense-mediated decay, causing a WS-like cardiovascular phenotype without WS. ELN frameshift mutations result in abnormal elastin production, leading to vascular stenosis. More than 100 ELN variants exist, and this mutation was located on exon 6 in our patient. Broader genetic evaluation beyond microarray is crucial in unexplained congenital vascular stenoses.

Conclusion: This case reveals a pathogenic ELN variant mutation mimicking WS cardiovascular features. Advanced genetic testing, including exon sequencing, is critical for the precise diagnosis and management of congenital vascular disorders.