BACKGROUND: In the spectrum of children with symptomatic sleep disordered breathing (SDB), some individuals - such as those with upper airway resistance syndrome (UARS) - do not have abnormalities on polysomnography (PSG). In this study we have assessed whether assessment of respiratory arrhythmia (RA) and heart rate variability (HRV) analysis helps in management of children with syndromic craniosynostosis and none-to-mild obstructive sleep apnea (OSA). METHODS: Prospective cohort study in children aged 1-18 years old with syndromic craniosynostosis. Children were selected for HRV analysis from the ECG if their obstructive apnea-hypopnea index (oAHI) was between zero and five per hour (ie, oAHI </=5/hour). Subjects were divided into groups based on the presence or absence of respiratory arrhythmia (with or without RA respectively) using the electrocardiogram (ECG). The main analysis included studying the relationship between RA and HRV, symptoms, interventions, and sleep architecture. RESULTS: We identified 42 patients with, at worst, mild OSA. We found higher parasympathetic control and higher total power in children with RA during the non-rapid eye movement (non-REM) sleep. Children with RA also have a relatively higher percentage of paradoxical breathing during non-REM sleep (P = 0.042). Intracranial hypertension was distributed equally between groups. Last, RA patients showed increased parasympathetic activity that further increased in non-REM sleep. CONCLUSION: In syndromic craniosynostosis cases with SDB and PSG showing oAHI </=5/hour, the presence of RA may indicate subsequent need for treatment interventions, and a trend toward higher occurrence of clinical symptoms. ECG analyses of HRV variables in subjects with RA demonstrate increased parasympathetic activity and total power. Such findings may add to the diagnosis of apparently asymptomatic children.