Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome

Abstract

BackgroundRett syndrome is a severe neurological disorder with a range of disabling autonomic and respiratory symptoms and resulting predominantly from variants in the methyl-CpG binding protein 2 gene on the long arm of the X-chromosome. As basic research begins to suggest potential treatments, sensitive measures of the dynamic phenotype are needed to evaluate the results of these research efforts. Here we test the hypothesis that the physiological fingerprint of Rett syndrome in a naturalistic environment differs from that of controls, and differs among genotypes within Rett syndrome.MethodsA comprehensive array of heart rate variability, cardiorespiratory coupling and cardiac repolarisation measures were evaluated from an existing database of overnight and daytime inhome ambulatory recordings in 47 cases and matched controls.ResultsDifferences between girls with Rett syndrome and matched controls were apparent in a range of autonomic measures, and suggest a shift towards sympathetic activation and/or parasympathetic inactivation. Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls.ConclusionsComprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies.

Breathing Abnormalities During Sleep and Wakefulness in Rett Syndrome: Clinical Relevance and Paradoxical Relationship With Circulating Pro-oxidant Markers

“…Although the small sample size prevents general conclusions, our findings suggest a link between specific types of MECP2 mutations (i.e., R255X, large deletions, and R106W) and cardiorespiratory monitoring findings. In particular, our observation of a positive link between recorded total breath holding episodes and R270X MECP2 mutations appears in line with prior observations by Carroll et al ( 71 ) of major alterations in amplitude and phase of autonomic balance diurnal patterns observed in patients with RTT with early truncating MECP2 mutations. In contrast, a prior natural history study on a large RTT cohort has evidenced breathing dysfunction not being related to specific mutations with the presence of MECP2 mutation as the only genetic factor being associated with breathing dysfunction ( 28 ).…”

“…Indeed, in our personal extended database, mean systolic blood pressure and diastolic blood pressure values correspond to 0.95 ± 0.1 (value range 0.81–1.24) and 0.92 ± 0.12 (0.73–1.18) multiple of medians compared to age- and gender-matched healthy control subjects (individual data not shown). In line with the well-known cardiac autonomic dysfunction ( 68 , 70 , 71 ), resting awake heart rate values were found to be increased, corresponding to 1.1 [0.98–1.30] (0.90–1.74) multiple of medians for age- and gender-matched healthy population (individual data not shown; JH, CDF, VS, RC, personal observation).…”

“…Dysregulation of autonomic circuits is a key feature of RTT ( 68 – 70 ), with diurnal variation in the autonomic regulation and shift toward sympathetic activation and/or parasympathetic inactivation ( 71 ).…”

Risk Factors for Patient–Ventilator Asynchrony and Its Impact on Clinical Outcomes: Analytics Based on Deep Learning Algorithm

“…Pathophysiologically, DT is the result of high inspiratory demand and excessive inspiratory effort (23). Inspiratory demand can be high during daytime because of the diurnal variation pattern (24). Furthermore, patients are more likely to be awake and influenced by medical procedures during day hours.…”

Rett syndrome severity estimation with the BioStamp nPoint using interactions between heart rate variability and body movement

“…Unfortunately, dysautonomia is a cardinal feature in Rett syndrome [7][8][9][10][11][12]. A principled approach to characterize dysautonomia is to utilize the electrocardiogram (ECG) [8,[13][14][15]. Researchers have used the ECG to study the variations in breathing and HR in Rett girls [16,17].…”