Hyperventilation

BackgroundPitt-Hopkins syndrome (PTHS; MIM# 610954) is a genetically determined entity mainly caused by mutations in TransCription Factor 4 (TCF4). We have developed a new way to collect information on (ultra-)rare disorders through a web-based database which we call 'waihonapedia' (waihona [meaning treasure in Hawaiian] encyclopaedia).MethodsWe have built a waihonapedia system in a collaboration between physicians, social scientists, and parent support groups. The system consists of an initial extensive questionnaire for background cross-sectional data, and subsequent follow-up using small questionnaires, with a particular focus on behavioural aspects. The system was built to be used through the internet, ensuring a secure environment, respecting privacy for participants, and acting automated to allow for low costs and limiting human mistakes in data handling. Recruitment of participants is through the patient support groups. In addition, as a sub-study, we used the data from the waihonapedia system to compare the two proposed diagnostic classification systems for PTHS.ResultsWe present here the results of the initial, cross-sectional questionnaire in which early development, physical health, cognition and behaviour are interrogated, and to which modules specific for PTHS were added on epilepsy and breathing patterns. We describe 101 individuals with a molecularly confirmed diagnosis of PTHS. Comparison of the two classification systems aimed at helping the clinical diagnosis was performed in 47 of the present PTHS individuals, with disappointing results for both. Internationally accepted clinical diagnostic criteria are needed.ConclusionThe present cross-sectional data on the natural history of PTHS have yielded useful information which will further increase when follow-up data will be added. No doubt this will improve both care and research.

Panic disorder (PD), a complex anxiety disorder characterized by recurrent panic attacks, represents a poorly understood psychiatric condition which is associated with significant morbidity and an increased risk of suicide attempts and completed suicide. Recently however, neuroimaging and panic provocation challenge studies have provided insights into the pathoetiology of panic phenomena and have begun to elucidate potential neural mechanisms that may underlie panic attacks. In this regard, accumulating evidence suggests that acidosis may be a contributing factor in induction of panic. Challenge studies in patients with PD reveal that panic attacks may be reliably provoked by agents that lead to acid-base dysbalance such as CO2 inhalation and sodium lactate infusion. Chemosensory mechanisms that translate pH into panic-relevant fear, autonomic, and respiratory responses are therefore of high relevance to the understanding of panic pathophysiology. Herein, we provide a current update on clinical and preclinical studies supporting how acid-base imbalance and diverse chemosensory mechanisms may be associated with PD and discuss future implications of these findings.

High-altitude (HA) environments have adverse effects on the normal functioning body of people accustomed to living at low altitudes because of the change in barometric pressure which causes decrease in the amount of oxygen leading to hypobaric hypoxia. Sustained exposure to hypoxia has adverse effects on body weight, muscle structure and exercise capacity, mental functioning, and sleep quality. The most important step of acclimatization is the hyperventilation which is achieved by hypoxic ventilatory response of the peripheral chemoreceptors. Hyperventilation results in increase in arterial carbon-dioxide concentration. Altitude also affects sleep and cardiac output, which is the other determinant of oxygen delivery. Upon initial exposure to HA, the resting pulse rate increases rapidly, but with acclimatization, heart rate and cardiac output tend to fall. Another important component that leads to decrease in cardiac output is the reduction in the stroke volume with acclimatization. During sleep at HA, the levels of CO2 in the blood can drop very low and this can switch off the drive to breathe. Only after the body senses a further drop in O2 levels breathing is started again. Periodic breathing is thought to result from instability in the control system through the hypoxic drive or the response to CO2.

Kleefstra syndrome (KS) is a rare neurodevelopmental disorder associated with disruptions in the EHMT1 gene, often leading to intellectual disability, autism spectrum behaviors and epilepsy. The electroencephalogram (EEG) serves as a non-invasive tool to explore brain function in KS; yet, systematic characterizations of EEG features remain extremely limited. This review synthesizes current evidence on EEG findings in KS, highlighting the high prevalence of nonspecific abnormalities and seizures, but the absence of a consistent electrophysiological biomarker. Given the growing role of machine learning (ML) in extracting patterns from EEG data in related disorders-such as Angelman, Rett and Fragile X syndromes-this review explores how similar approaches could be adapted for KS. Despite promising perspectives, a lack of large-scale, publicly available EEG datasets hinders the application of ML methodologies in KS research. Future directions are proposed to address these gaps, including standardized EEG data collection, adoption of quantitative EEG analyses and integration of ML techniques adapted for small datasets. This multidisciplinary strategy holds potential for improving early diagnosis, monitoring and personalized interventions in Kleefstra syndrome.