Familial recurrence and phenotype concordance in non-syndromic congenital heart disease: A tertiary care center study from India

Objectives: Congenital heart disease (CHD) is the most common congenital anomaly, yet robust familial recurrence data from the South Asian region remain limited despite a high regional burden. This study estimates familial recurrence risk and evaluates phenotype concordance in multi-affected, non-syndromic CHD families from India. Methods: This retrospective pedigree-based study included 109 multi-affected, non-syndromic CHD families (3,241 relatives) treated at a tertiary cardiac centre. Detailed three- to four generation pedigrees were constructed, and echocardiographically confirmed CHD status was assessed. Recurrence risks, adjusted risk ratios (ARRs), and phenotype concordance were analyzed according to degree of kinship and familial clustering. Results: The overall recurrence risk among relatives, excluding probands, was 4.07% (95% confidence interval: 3.44– 4.81). First-degree relatives showed a markedly elevated risk (20.73%; ARR = 9.31, p < 0.001), with siblings demonstrating the highest recurrence compared to parents (38.04% vs. 7.80%; ARR = 5.04, p < 0.001). Recurrence increased with familial clustering (ARR = 2.14 for ≥3 affected members, p < 0.001). Phenotype concordance was moderate overall but high for septal defects (71.93%) and cyanotic status (83.52%), particularly among first-degree relatives. Conclusion: These findings suggest familial aggregation in a high-risk familial subset from a tertiary-care centre and provide regionally important evidence from an under-represented population; however, their implications for screening strategies require confirmation in population-based studies.