MicroRNA-495 Modulates Neuronal Layer Fate Determination by Targeting .

During cortical development, the differentiation potential of neural progenitor cells (NPCs) is one of the most critical steps in normal cortical formation and function. Defects in this process can lead to many brain disorders. MicroRNA dysregulation in the dorsolateral prefrontal cortex is associated with risk for a variety of developmental and psychiatric conditions.

Breathing Pattern Disorder: Introduction and Diagnostics.

Breathing pattern disorder (BPD) refers to a heterogenous condition, which features altered normal respiratory functioning that cannot be fully attributed to organic causes at the current time. Characteristic symptoms of this condition include dyspnea, and irregular ventilation. The diagnosis of BPD is made utilizing a combination of patient-reported experiences in the form of validated questionnaires, direct observation by experienced clinicians, and objective testing in the form of cardiopulmonary exercise testing.

[Clinical and genetic characteristics of children with Pitt-Hopkins syndrome caused by TCF4 gene variants].

The clinical data of children with Pitt-Hopkins syndrome (PTHS) who were treated in the Affiliated Women and Children's Hospital of Ningbo University from September 2022 to January 2024 were retrospectively included. The patients were followed up to June 2024, and their clinical and genetic characteristics were analyzed. A total of 4 children were included, 2 males and 2 females, with a diagnostic age [M (Q, Q)] of 22 (10, 32) months.

A novel variant in the 3' UTR of the TCF4 gene likely causes Pitt-Hopkins syndrome: a case report.

Background: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder that results from variants of TCF4 gene. PTHS follows an autosomal dominant inheritance pattern and the underlying pathological mechanisms of this disease are still unclear.

Methods: Whole-genome sequencing (WGS) was conducted to screen for potential pathogenic variant in a boy highly suspected of having a genetic disorder.

Exploring Kleefstra syndrome cohort phenotype characteristics: Prevalence insights from caregiver-reported outcomes.

Kleefstra syndrome (KLEFS1) is a rare genetic neurodevelopmental disorder affecting multiple body systems. It continues to be under-researched, and its prevalence remains unknown. This paper builds on the international KLEFS1 cohort of 172 individuals based on the caregiver-reported outcomes collected within the online data collection platform GenIDA and reports the occurrence, frequency and severity of symptoms in KLEFS1.

Reduced Stroke Volume and Brain Perfusion Drive Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome.

Postural hyperventilation has been implicated as a cause of postural orthostatic tachycardia syndrome (POTS), yet the precise mechanisms underlying the heightened breathing response remain unclear. This study challenges current hypotheses by revealing that exaggerated peripheral chemoreceptor activity is not the primary driver of postural hyperventilation. Instead, significant contributions from reduced stroke volume and compromised brain perfusion during orthostatic stress were identified.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control.

A Review of Hyperventilation Activation in Diagnosis and Management of Childhood Absence Epilepsy.

Childhood absence epilepsy is one of the most prevalent pediatric epilepsy syndromes, but diagnostic delay is common and consequential. Childhood absence epilepsy is diagnosed by history and physical examination including hyperventilation with electroencephalography (EEG) used to confirm the diagnosis. Hyperventilation produces generalized spike-wave discharges on EEG in >90% of patients with childhood absence epilepsy and provokes clinical absence seizures consisting of brief loss of consciousness typically within 90 seconds.

Unraveling persistent dyspnea after mild COVID: insights from a case series on hyperventilation provocation tests.

Dyspnea is a common yet poorly understood symptom of long COVID, affecting many patients. This brief report examines the role of dysfunctional breathing in persistent dyspnea among patients with mild post-COVID-19 using hyperventilation provocation tests (HVPT). In this case series, six patients with unexplained dyspnea and normal cardiopulmonary function underwent HVPT.

[Dyspnea in post-COVID-19 patients: A review].

New coronavirus infection may lead to long-term consequences, particularly to post-COVID syndrome, one of the most common manifestations of which is dyspnea. Post-COVID-19 shortness of breath may persist from one to several months and even years that results in low quality of life of patients. The review highlights possible risk factors and causes of dyspnea in post-COVID period such as lung damage, cardiovascular pathology, hyperventilation syndrome, dysfunction of the autonomic nervous system, detraining, anemia, etc.

Skeletal muscle vulnerability in a child with Pitt-Hopkins syndrome.

Background: TCF4 acts as a transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5 motif. Dominant variants in TCF4 are associated with the manifestation of Pitt-Hopkins syndrome, a rare disease characterized by severe mental retardation, certain features of facial dysmorphism and, in many cases, with abnormalities in respiratory rhythm (episodes of paroxysmal tachypnea and hyperventilation, followed by apnea and cyanosis). Frequently, patients also develop epilepsy, microcephaly, and postnatal short stature.

A case of middle-aged central sleep apnea due to Joubert syndrome with different treatment effects of oxygen and acetazolamide.

Unlabelled: We report a case of severe central sleep apnea incidentally diagnosed during polysomnography for suspected obstructive sleep apnea. Characteristic clinical features included episodic hyperventilation followed by apnea from hypocapnia, which did not follow a Cheyne-Stokes pattern. Combined with the identification of cerebellar and brainstem malformations known as the "molar tooth sign" on a brain magnetic resonance imaging, developmental delay, and motor coordination problems, Joubert syndrome (a congenital disease) was first diagnosed at the age of 50 years.

MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.

The neurodevelopmental disorder Pitt Hopkins syndrome (PTHS) causes clinical symptoms similar to Rett syndrome (RTT) patients. However, RTT is caused by MECP2 mutations whereas mutations in the TCF4 gene lead to PTHS. The mechanistic commonalities underling these two disorders are unknown, but their shared symptomology suggest that convergent pathway-level disruption likely exists.

EEG in focal and generalized epilepsies: Pearls and perils.

Correctly diagnosing and classifying seizures and epilepsies is vital to ensure a tailored approach to patients with epilepsy. The ILAE seizure classification consists of two main groups: focal and generalized. Establishing if a seizure is focal or generalized is essential to classify the epilepsy type and the epilepsy syndrome, providing more personalized treatment and counseling about prognosis.

Expanding the phenotype in Pitt-Hopkins syndrome; description of new oral finding and dental management considerations.

Background: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder with physical, cognitive, and behavioral characteristics that is caused by heterozygous mutations in the TCF4 gene. Patients with PTHS might present a unique challenge for oral healthcare professionals because of the associated comorbidities.

Case Report: Here we describe a new case of PTHS in a 13-year-old girl with particular emphasis on oro-dental findings and oral healthcare management.

A case of Pitt-Hopkins syndrome: psychopharmacological approach for anxiety, insomnia, and agitation.

Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder resulting from TCF4 gene mutations which is characterized by dysmorphic facial features, psychomotor delay, intellectual disability, breathing anomalies, and seizures. Psychiatric conditions are occasionally seen. We present the case report of a seven-year-old PTHS patient with anxiety, insomnia, and agitation.

Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CB) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.

Tcf4 dysfunction alters dorsal and ventral cortical neurogenesis in Pitt-Hopkins syndrome mouse model showing sexual dimorphism.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by haploinsufficiency of transcription factor 4 (TCF4). In this work, we focused on the cerebral cortex and investigated in detail the progenitor cell dynamics and the outcome of neurogenesis in a PTHS mouse model. Labeling and quantification of progenitors and newly generated neurons at various time points during embryonic development revealed alterations affecting the dynamic of cortical progenitors since the earliest stages of cortex formation in PTHS mice.

Validity and reliability of outcome measures to assess dysfunctional breathing: a systematic review.

Objective: This study aimed to systematically review the psychometric properties of outcome measures that assess dysfunctional breathing (DB) in adults.

Methods: Studies on developing and evaluating measurement properties to assess DB were included. The study investigated the empirical research published between 1990 and February 2022, with an updated search in May 2023 in the Cochrane Library database of systematic reviews and the Cochrane Central Register of Controlled Trials, the Ovid Medline (full), the Ovid Excerta Medica Database, the Ovid allied and complementary medicines database, the Ebscohost Cumulative Index to Nursing and Allied Health Literature and the Physiotherapy Evidence Database.

DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by pathogenic variants in TCF4, leading to intellectual disability, specific morphological features, and autonomic nervous system dysfunction. Epigenetic dysregulation has been implicated in PTHS, prompting the investigation of a DNA methylation (DNAm) "episignature" specific to PTHS for diagnostic purposes and variant reclassification and functional insights into the molecular pathophysiology of this disorder. A cohort of 67 individuals with genetically confirmed PTHS and three individuals with intellectual disability and a variant of uncertain significance (VUS) in TCF4 were studied.