Complex
neurodevelopmental disorders need multi-disciplinary treatment approaches for optimal care. The clinical effectiveness of treatments is limited in patients with rare genetic syndromes with multisystem morbidity. Emotional and behavioural dysregulation is common across many
neurodevelopmental disorders. It can manifest in children across multiple diagnostic groups, including those on the
autism spectrum and in rare genetic syndromes such as
Rett Syndrome (RTT). There is, however a remarkable scarcity in the literature on the impact of the autonomic component on emotional and behavioural regulation in these disorders, and on the longer-term outcomes on disorder burden.RTT is a debilitating and often life-threatening disorder involving multiple overlapping physiological systems. Autonomic dysregulation otherwise known as
dysautonomia is a cardinal feature of RTT characterised by an imbalance between the sympathetic and parasympathetic arms of the autonomic nervous system. Unlocking the autonomic component of emotional and behavioural dysregulation would be central in reducing the impairment seen in patients with RTT. In this vein, Emotional, Behavioural and Autonomic Dysregulation (
EBAD) would be a useful construct to target for treatment which could mitigate burden and improve the quality of life of patients.RTT can be considered as a congenital
dysautonomia and because
EBAD can give rise to impairments occurring in multiple overlapping physiological systems, understanding these physiological responses arising out of
EBAD would be a critical part to consider when planning treatment strategies and improving clinical outcomes in these patients. Biometric guided pharmacological and bio-feedback
therapy for the behavioural and emotional aspects of the disorder offers an attracting perspective to manage
EBAD in these patients. This can also allow for the stratification of patients into clinical trials and could ultimately help streamline the patient care pathway for optimal outcomes.The objectives of this review are to emphasise the key issues relating to the management of
EBAD in patients with RTT, appraise clinical trials done in RTT from the perspective of autonomic physiology and to discuss the potential of
EBAD as a target for clinical trials.