A Novel Missense Heterozygous Mutation in NKX2-5 Gene in a Family with Congenital Septal Defects and Cardiomyopathy: Case Series and Literature Review

Abstract

Single-gene mutations are important causes of congenital heart defects in children. Mutations in the NKX2-5 gene have been recently described in the literature as a cause of septal defects and cardiomyopathy. However, the spectrum of cardiac disease associated with NKX2-5 gene mutations is variable, ranging from asymptomatic septal defects to cardiomyopathy and sudden death. In this case report, we describe a case of 2-year-old child, along with two other family members, with a novel missense heterozygous (c.544G > T p.[Val182Phe]) mutation in NKX2-5 gene consistent with the diagnosis of autosomal dominant atrial septal defects with cardiomyopathy. This report can contribute to the understanding of genotype–phenotype correlations; it emphasizes the significant clinical relevance of NKX2-5 gene defects for congenital heart defects, sudden death, and cardiomyopathy, especially in multiple affected family members. It also suggests that individuals with NKX2-5 mutations are at risk of lethal arrhythmias and conduction disorders, that is why they should be evaluated routinely to assess the need for implantable cardioverter-defibrillator or pacemaker implantation.

Keywords

NKX2-5 gene - congenital heart diseases - atrial septal defect - ventricular septal defect - cardiomyopathy

Patient Consent

Consent for publication was obtained from the reported family.

Ethical Approval

This study was approved by our regional research ethics committee. Ref. No.: KD/AJ/88

Authors' Contributions

The authors contributed to the conception and design. All authors contributed to the acquisition and revised manuscript and agreed to be accountable for all aspects of the work, ensuring integrity and accuracy. All authors read and approved the final manuscript.

Publication History

Received: 14 May 2023

Accepted: 10 June 2024

Article published online:
10 July 2024

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