Key result
Ogden Syndrome NAA15 interaction domain variants are linked to ~160% more cardiac abnormalities than outside variants.
Why the study?
Although cardiac manifestations of Ogden Syndrome have been described in case reports, studies focusing on its cardiac manifestations and clinical management recommendations were lacking.
Cohort (n=85)
Yes
Absolute Event Rate: 3.9% vs 1.5%
p-value: p=0.003
Ogden Syndrome is associated with a high burden of structural and electrophysiologic cardiac abnormalities, particularly prolonged QTc, necessitating routine baseline and follow-up cardiac screening.
May support variant-specific monitoring in Ogden syndrome; leaves open need for prospective validation.
The NatA complex is composed of the NAA10, NAA15, and HYPK sub-units. It is primarily responsible for N-terminal acetylation, a critical post-translational modification in eukaryotes. Pathogenic variants within NAA10 cause Ogden Syndrome (OS), which is characterized by varying degrees of intellectual disability, hypotonia, developmental delay, and cardiac abnormalities. Although the cardiac manifestations of the disease have been described extensively in case reports, there has not been a study focusing on the cardiac manifestations and their recommended clinical cardiac management. In this study, we describe the cardiac manifestations of OS in a cohort of 85 probands. We found increased incidence of structural and electrophysiologic abnormalities, with particularly high prevalence of QT interval prolongation. Sub-analysis showed that male probands and those with variants within the NAA15-binding domain had more severe phenotypes than females or those with variants outside of the NAA15-binding domain. Our results suggest that an OS diagnosis should be accompanied by full cardiac workup with emphasis on echocardiogram for structural defects and EKG/Holter monitoring for electrophysiologic abnormalities. Additionally, we strongly recommend that the use of QT-prolonging drugs be followed up with routine electrophysiological monitoring or consultation with a pediatric cardiologist. We hope this study guides clinicians and caregivers treating patients with OS and moves the field toward a standardized diagnostic workup for patients with this condition.
No takes yet. Share an insight, caveat, or question.
Makwana et al. (2025) conducted a cohort in Ogden Syndrome (NAA10-related neurodevelopmental syndrome) (n=85). Variants within the NAA15 interaction domain vs. Variants outside the NAA15 interaction domain was evaluated on Average number of cardiac abnormalities per proband (p=0.003). In probands with Ogden Syndrome, variants within the NAA15 interaction domain were associated with a significantly higher average number of cardiac abnormalities (3.9) compared to variants outside the domain (1.5).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: