P261: Addressing undiagnosed diseases in a developing nation: The Indian Undiagnosed Diseases Program

From positive genetic diagnoses, diagnostic variants were described by genotype characteristics: Single Nucleotide Variants (SNVs) or Copy Number Variants (CNVs).CNVs were organized as microduplications, microdeletions, or aneuploidies.SNVs were classified as intronic or exonic and further as substitutions, insertions, deletions, or indels, with biological roles analyzed via Panther.Length of stay (LOS) was the primary hospital outcome studied.Chi-squared, Fisher's exact, Mantel-Haenszel, and Wilcoxon tests were used to assess statistical differences in the genetic diagnosis rates and LOS among comparison groups.Results: The majority of the cohort had anomalies in multiple systems compared to a single system (59% vs 41%), with a higher genetic diagnosis rate in the "More Than One System" group compared to the "Isolated System" group (32% vs 21.3%, p=0.04).Of the cohort, 71.4% had anomalies in cardiac, 12.8% in digestive, 29.0% in genitourinary, 29.3% in head/neck/eye/ear, 20.9% in musculoskeletal, 13.8% in nervous, 10.8% in pulmonary, and 5.4% in other.Among the 82 diagnosed patients, 38 CNVs (60.5% microdeletions) and 47 SNVs (87.2% exonic, 63.8% substitutions) were identified.Panther analysis of 41 unique SNV genes showed the top three biological processes were cellular processes, biological regulation, and developmental processes (63.4%).In the "Isolated System" group, patients with a genetic diagnosis had a longer LOS (median 94 vs 16 days, p = 0.005).In the "More Than One System" group, the presence or absence of a genetic diagnosis did not affect LOS (median 30.5 vs 35 days, p > 0.05).Conclusion: NICU patients present with a wide range of congenital anomalies across organ systems.While anomalies in multiple organ systems predicted a greater chance of a genetic diagnosis after GS, a significant number of patients with anomalies in one organ system received a genetic diagnosis, highlighting the utility of GS in this population.Genes linked to congenital anomalies in a NICU cohort are often involved in ubiquitous cellular functions expressed across multiple organ systems and cause early symptomatic disease when carrying pathologic variants.While most patients had SNVs, a significant minority had CNVs, highlighting the superiority of GS to detect a variety of genetic mechanisms which result in congenital anomalies.Patients with congenital anomalies had LOSs extending beyond the neonatal period, with patients having an isolated system anomaly and a genetic diagnosis experiencing the longest hospitalizations.Further study is needed to understand the detectable rate of genetic disease in patients with congenital anomalies and how a genetic diagnosis impacts the NICU stay.