Endocrine Abnormalities and Growth Characterization in Colombian Pediatric Patients with 22q11 Deletion Syndrome

Objective: Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition. Methods: A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted. Results: Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate. Conclusion: As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate.

Agency Deficits in a Human Genetic Model of Schizophrenia: Insights From 22q11DS Patients.

Schizophrenia is a chronic and disabling mental illness characterized by a disordered sense of self. Current theories suggest that deficiencies in the sense of control over one's actions (Sense of Agency, SoA) may underlie some of the symptoms of schizophrenia. However, it is not clear if agency deficits are a precursor or a result of psychosis. Here, we investigated full body agency using virtual reality in a cohort of 22q11 deletion syndrome participants with a genetic propensity for schizophrenia. In two experiments employing virtual reality, full body motion tracking, and online feedback, we investigated SoA in two separate domains. Our results show that participants with 22q11DS had a considerable deficit in monitoring their actions, compared to age-matched controls in both the temporal and spatial domain. This was coupled with a bias toward erroneous attribution of actions to the self. These results indicate that nonpsychotic 22q11DS participants have a domain general deficit in the conscious sensorimotor mechanisms underlying the bodily self. Our data reveal an abnormality in the SoA in a cohort with a genetic predisposition for schizophrenia, but without psychosis, providing evidence that deficits in delineation of the self may be a precursor rather than a result of the psychotic state.

Bleeding Severity and Phenotype in 22q11.2 Deletion Syndrome-A Cross-Sectional Investigation.

OBJECTIVES: To prospectively quantify bleeding severity and elaborate hemorrhagic symptoms in children with 22q11.2 deletion syndrome (22q11DS) using 2 validated bleeding assessment tools (BATs), namely the Pediatric Bleeding Questionnaire and the International Society on Thrombosis and Hemostasis BAT (ISTH-BAT). We also sought to compare subjects' bleeding scores to unaffected first-degree family members. STUDY DESIGN: Children with 22q11DS and unaffected first-degree family members were recruited for the study. Two validated BATs were administered by a pediatric hematologist. Additional clinical and laboratory data were abstracted from patient medical records. Standard descriptive and nonparametric statistical methods were used. RESULTS: In total, 29 eligible subjects and controls were assessed. Median age (range) of subjects and controls was 8 (5-17) years and 38 (9-56) years, respectively. In total, 17 of 29 subjects had a positive bleeding score on ISTH-BAT compared with 1 of 29 control patients (P < .0001). Median ISTH-BAT score in subjects was 3 (0-12), compared with 2 (0-6) in control patients (P = .022). Median Pediatric Bleeding Questionnaire score in subjects was 2 (-1 to 12). The most frequent bleeding symptoms reported in subjects with 22q11DS were epistaxis (69%) and bruising (52%). Eighteen subjects had been surgically challenged, and 6 were noted to have increased perioperative hemorrhage. CONCLUSIONS: Children with 22q11DS have increased bleeding scores compared with their first-degree unaffected relatives. The majority of the bleeding symptoms described were mucocutaneous.

Lymphoproliferative disorder with polyautoimmunity and hypogammaglobulinemia: An unusual presentation of 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) has a heterogeneous presentation that includes multiple congenital anomalies and immunodeficiency, one of the most striking features. Usually, it is characterized by T cell lymphopenia, B cell dysfunction and autoimmunity. Here, we describe an unusual case of 22q11.2DS in a patient with lymphoproliferative disorder, polyautoimmunity and hypogammaglobulinemia.

[The language of children and young people with 22q11 deletion syndrome]. / Lenguaje de niños y jóvenes con síndrome de deleción 22q11.

INTRODUCTION: The 22q11 deletion syndrome (S22q11) is one of the most prevalent genetic disorders, resulting in multiple systemic and neuropsychological features. AIM: To describe the language profile in a sample of Spanish subjects with S22q11. PATIENTS AND METHODS: A sample of 30 Spanish participants with S22q11 aged between 5 years and 21 years and 11 months (mean: 12.14 ± 4.20 years) was evaluated using standardized tests and a questionnaire administered to parents. RESULTS: Almost half of the subjects obtained better results in expressive language than in comprehensive language and the majority obtained a higher score in language content than in language memory. The results suggest that people with S22q11 present language difficulties that improve with age to a certain level and subsequently stabilize. A specific profile is observed that suggests that pragmatic difficulties are a consequence of this language profile and not only of social difficulties already described in this pathology. CONCLUSIONS: In the sample of the present study, children and young people with S22q11 present specific language and pragmatic disorders. More than half of the study participants did not obtain significant differences between the level of expressive and receptive language. Most presented semantic fluency difficulties. The type and degree of impairment in pragmatic skills suggest that the basic problem may be related to their language difficulties.

TITLE: Lenguaje de niños y jóvenes con síndrome de deleción 22q11.Introducción. El síndrome de deleción 22q11 (S22q11) es uno de los trastornos genéticos más prevalentes, y presenta múltiples alteraciones sistémicas y neuropsicológicas. Objetivo. Describir el perfil de lenguaje y pragmática asociado a este síndrome. Pacientes y métodos. Se evaluó una muestra de 30 participantes españoles con S22q11 de edades comprendidas entre 5 años, y 21 años y 11 meses (media: 12,14 ± 4,2 años) mediante pruebas estandarizadas y un cuestionario administrado a los padres. Resultados. Casi la mitad de la muestra obtuvo mejores resultados en el lenguaje expresivo que en el comprensivo, y la mayoría logró una mayor puntuación en el contenido del lenguaje que en la memoria del lenguaje. Los resultados sugieren que las personas con S22q11 presentan dificultades de lenguaje que mejoran con la edad hasta cierto nivel y, posteriormente, se estabilizan. Se observa un perfil específico que sugiere que las dificultades pragmáticas son consecuencia de este perfil de lenguaje y no sólo de dificultades sociales ya descritas en esta patología. Conclusiones. En la muestra del presente estudio, los niños y jóvenes con S22q11 presentan alteraciones específicas del lenguaje y la pragmática. Más de la mitad de los participantes del estudio no obtuvieron diferencias significativas entre el nivel de lenguaje expresivo y el receptivo. La mayoría presentó dificultades de fluencia semántica. El tipo y el grado de las alteraciones que presentan en las habilidades pragmáticas sugieren que el problema básico podría estar relacionado con sus dificultades lingüísticas.

Congenital Heart Disease Revealing Familial 22q11 Deletion Syndrome

Abstract Congenital heart defects are the most common birth defects and the leading cause of mortality in the first year of life. It is well known that the 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and that congenial heart diseases (CHDs) are one of the most common phenotypic manifestations. However, it should be noted that the 22q11 deletion was also found in a significant number of patients with isolated CHD. The 22q11DS phenotype may include cardiovascular anomalies, palatal abnormalities, nasal voice, immune deficiency, endocrine dysfunctions, a varying degree of cognitive deficits and intellectual disabilities, velopharyngeal insufficiency, and characteristic craniofacial dysmorphism. This condition affects about 1 in 4,000 live births, making 22q11DS the most common microdeletion syndrome in humans. Here we describe the cases of three children who were referred to the clinical hospital center with the diagnosis of CHD, but with no direct signs of 22q11DS. Investigation of familial data led us to suspect that the mothers could be carriers of 22q11DS. The multiplex ligation-dependent probe amplification (MLPA) testing confirmed that the patients and mothers exhibited 3 Mb 22q11 deletions, which justified the clinical signs in the mothers and the CHD in children. In the presence of a few characteristics that are common of a spectrum of some known syndromes, a familial examination can provide clues to a definitive diagnosis, as well as to the prevention of diseases and genetic counseling of these patients.

A rare case of tympanostomy tube otorrhea: Pigmentiphaga.

Tympanostomy tube otorrhea (TTO) is a common complication of tympanostomy tubes. The most common bacteria associated with TTO include Haemophalis influenza, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. We present the first case of a 9 year-old female with a history of 22q11 syndrome, hemifacial microsomia, Tetralogy of Fallot, and hearing aid dependence with left-sided profound sensorineural and right-sided moderate conductive hearing loss who presented with TTO caused by the bacteria Pigmentiphaga daeguenesis/kulla, a gram-negative bacteria often found in soil. This patient's otorrhea did not respond to typical otic antibiotic formulations, but was ultimately treated successfully with intramuscular ceftriaxone. We describe the natural history, presentation and management for a case of TTO caused by a rare bacteria from the genus Pigmentiphaga.

Sleep patterns and problems among children with 22q11 deletion syndrome.

BACKGROUND: To delineate sleep habits and problems in children with 22q11.2 deletion syndrome (22q11DS). METHODS: Thirty children, age 1-15 (mean 6.8) years, participated in the study, which was an internet-based anonymous survey of parents of children with 22q11DS administered via the 22q11.2 Foundation. The main outcome was the Childhood Sleep Habits Questionnaire (CSHQ). RESULTS: Scores on the CSHQ demonstrated clinically significant sleep problems in 29 of the 30 children. When compared with previously reported normative values for typically developing children of the same age, children with 22q11DS had significantly greater sleep problems. Only 30% of children had previously undergone sleep study. While about half of children had tried a medication for sleep, it usually was not felt to be helpful. In contrast, parents reported that behavioral interventions, such as consistent bedtime routine and appropriate sleep environment, were helpful. This is one of the first studies to specifically address sleep problems other than obstructive sleep apnea in children with 22q11DS. CONCLUSIONS: The findings suggest children with 22q11DS may have a higher risk of experiencing clinical sleep problems, compared to typically developing children. Consideration of additional screening and treatment of sleep disorders in children with 22q11DS is warranted.

Associated syndromes in patients with Pierre Robin Sequence.

OBJECTIVES: Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current literature reports that Stickler syndrome is the most common syndrome associated with PRS, and 22q11 deletion syndrome (22q11 DS) as the second most common. This study identifies associations between PRS and genetic syndromes. METHODS: A retrospective chart review was performed to identify patients diagnosed with PRS over a 10-year period from 4/1/2007 to 4/1/2017 at a tertiary children's hospital. RESULTS: 4,052 consecutive charts were reviewed and 234 patients had a diagnosis of PRS confirmed with the triad of micrognathia, glossoptosis, and airway obstruction. Of note, all of these patients had cleft palate. Of the 234 patients with PRS, 65 patients had syndromic diagnoses (28%). One patient had 22q11 DS (0.43%), and 31 patients had Stickler syndrome (13.2%). Additionally, 3 patients had central hypoventilation syndrome, 3 patients had Duane syndrome, 2 patients had Cornelia de Lange syndrome, 2 patients had Emanuel syndrome, 2 patients had Gordon syndrome, 2 patients had Mobius syndrome, 2 patients had Nager syndrome. Multiple other syndromes were identified, but occurred in isolated cases. CONCLUSION: This study supports literature that PRS is most commonly associated with Stickler Syndrome but rarely associated with 22q11 DS given that only 1 patient had both PRS and 22q11 DS.

Origen anómalo de la arteria subclavia izquierda / Anomalous origin of the left subclavian artery

No disponible

Seeing Eye to Eye With Threat: Atypical Threat Bias in Children With 22q11.2 Deletion Syndrome.

Individuals with 22q11.2 deletion syndrome (22q11DS) show high rates of anxiety associated with their increased risk of developing schizophrenia. Biased attention is associated with anxiety and is important to investigate in those with 22q11DS given this association. We analyzed attention bias to emotional faces in 7- to 17-year olds with 22q11DS and typically developing controls (TD) using a dot probe threat bias paradigm. We measured response time, eye tracking, and pupilometry. Those with 22q11DS showed no significant changes in early versus late trials, whereas those who were TD showed differing patterns in both gaze and pupilometry over time. The patterns in those who are TD may indicate adaptation that is lacking or slower in individuals with 22q11DS.

Speech-Language Disorders in 22q11.2 Deletion Syndrome: Best Practices for Diagnosis and Management.

Purpose Speech and language disorders are hallmark features of 22q11.2 deletion syndrome (22qDS). Learning disabilities, cognitive deficits, palate abnormalities, velopharyngeal dysfunction, behavioral differences, and various medical and psychiatric conditions are also major features of this syndrome. The goal of this document is to summarize the state of the art of current clinical and scientific knowledge regarding 22qDS for speech-language pathologists (SLPs) and provide recommendations for clinical management. Method Best practices for management of individuals with 22qDS were developed by consensus of an expert international group of SLPs and researchers with expertise in 22qDS. These care recommendations are based on the authors' research, clinical experience, and literature review. Results This document describes the features of 22qDS as well as evaluation procedures, treatment protocols, and associated management recommendations for SLPs for the often complex communication disorders present in this population. Conclusion Early diagnosis and appropriate management of speech-language disorders in 22qDS is essential to optimize outcomes and to minimize the long-term effects of communication impairments. Knowledge of this diagnosis also allows anticipatory care and guidance regarding associated features for families, health care, and educational professionals.

Neurocognitive profile and onset of psychosis symptoms in children, adolescents and young adults with 22q11 deletion syndrome: A longitudinal study.

BACKGROUND: The neurobehavioral phenotype of 22q11.2 deletion syndrome (22q11DS) includes cognitive dysfunction and high rates of psychotic symptoms and schizophrenia. Existing research has mainly considered changes in IQ, especially its decline, as a psychosis predictor. The aim of this study was to investigate, in a longitudinal perspective, the relationship between neuropsychological abilities (not only IQ but also executive functioning, language and visual-motor integration abilities) and onset of psychotic symptoms in a sample of children, adolescents and young adults with 22q11DS. In addition, the role of comorbid psychiatric disorders at baseline was taken into account. METHODS: 75 participants with 22q11DS, aged between 6 and 27 years at baseline, were included. Eighteen of the 75 participants had developed psychosis at the one year follow-up (onset psychosis-OP) and constituted the first group; 57 participants who had not developed a psychosis at the one year follow-up (without onset psychosis-WOP) constituted the second group. RESULTS: At baseline, group OP showed lower IQ (both full scale and verbal and performance scale) and more perseverative errors as well as a reduced number of correct categories on the Wisconsin Card Sorting Test (WCST) compared to group WOP. In addition, at baseline, group OP showed a higher frequency of depressive disorders than group WOP. CONCLUSION: Even if with caution, results suggest neuropsychological deficits and depressive symptoms should be considered and monitored as possible clinical signs for the onset of psychosis in children, adolescents and young adults with 22q11DS.

Bullying and psychosis: The impact of chronic traumatic stress on psychosis risk in 22q11.2 deletion syndrome - a uniquely vulnerable population.

Bullying is an adverse childhood experience that is more common among youth with special needs and is associated with increased psychopathology throughout the lifespan. Individuals with chromosome 22q11.2 deletion syndrome (22q) represent one group of special needs youth who are at increased risk for bullying due to co-occurring genetically-mediated developmental, physical, and learning difficulties. Furthermore, individuals with 22q are at increased risk for developing psychotic disorders such as schizophrenia. However, there is a paucity of research exploring the impact of bullying on individuals with 22q and the possible impact this has on risk for psychosis in this population. To explore this relationship using existing research the goals of the review are: (i) to explore the nature of bullying among youth with special needs, and (ii) to discuss its potential role as a specific risk factor in the development of adverse outcomes, including psychosis symptoms. We reviewed the relationship between bullying and its short and long-term effects on the cognitive, social, and developmental functioning of typically developing individuals and those with special needs. We propose an interactive relationship between trauma, stress, and increased psychosis risk among youth with 22q with a history of bullying. The early childhood experience of trauma in the form of bullying promotes an altered developmental trajectory that may elevate the risk for maladaptive functioning and subsequent psychotic disorders, particularly in youth with genetic vulnerabilities. Therefore, we conclude the experience of bullying among individuals with 22q should be more closely examined.

[Voice and speech of children with 22q11 deletion syndrome]. / Voz y habla de los niños con sindrome de delecion de 22q11.

INTRODUCTION: The 22q11 deletion syndrome (S22q11) is a genetic disorder caused by the loss of a fragment of the chromosome 22. The clinical manifestations associated with the syndrome are diverse, including learning difficulties and alterations in voice, speech and language. However, to date we have not found any study that evaluates these aspects in the Spanish population with S22q11. PATIENTS AND METHODS: We evaluate the voice and speech of a sample of 10 boys and 7 girls, aged 3 years and 3 months to 13 years and 9 months old (mean age: 9,4 ± 3,5 years old) with S22q11, with voice recordings and a phonological and phonetic evaluation. Also, semistructured type interview is administered to parents. RESULTS: Most children of our series, both male and female, with S22q11 have a deeper voice than expected by gender and age, except for male children over 12 years. In terms of intensity, all of them are within the parameters of normality in spontaneous conversation. Almost all of them showed alterations in voice quality, mainly due to hypernasality. Regarding the speech, there are major difficulties in the articulation of fricatives, affricates and vibrant rhotic consonant clusters + /r/. Likewise, children, especially the youngest ones, make use of glottal stops to replace consonants. CONCLUSIONS: In the studied sample, most of the children with S22q11 have specific voice and speech alterations.

TITLE: Voz y habla de los niños con sindrome de delecion de 22q11.Introduccion. El sindrome de delecion de 22q11 (S22q11) es un trastorno genetico causado por la perdida de un fragmento del cromosoma 22. Las manifestaciones clinicas que presenta quien lo padece son diversas, incluyendo dificultades del aprendizaje y alteraciones de la voz, el habla y el lenguaje. No obstante, hasta ahora no hemos encontrado ningun estudio que evalue estos aspectos en la poblacion española con el S22q11. Pacientes y metodos. Se evalua la voz y el habla de una muestra de 10 niños y 7 niñas, de 3 años y 3 meses a 13 años y 9 meses (edad media: 9,4 ± 3,5 años), con el S22q11, a traves de registros de voz y de una prueba de evaluacion fonologica y fonetica. Ademas, se realiza una entrevista semiestructurada a los padres. Resultados. La mayoria de los niños y las niñas con el S22q11 tienen una voz mas grave de lo esperable por su sexo y edad, a excepcion de los niños varones con mas de 12 años. En cuanto a la intensidad, todos ellos se encuentran dentro de los parametros de normalidad en la conversacion espontanea. Todos presentan alteraciones del timbre, principalmente por hipernasalidad. Respecto al habla, hay mayores dificultades en la articulacion de las fricativas, las africadas, la rotica vibrante (/r/) y los grupos consonanticos + /r/. Asimismo, los niños, sobre todo los mas pequeños, utilizan las oclusivas gloticas para sustituir consonantes. Conclusiones. En la muestra estudiada, la mayoria de los niños con el S22q11 presenta alteraciones especificas tanto de la voz como del habla.

[Child psychiatry interventions in patients with 22q11 deletion syndrome: From treatment to prevention]. / Prise en charge pédopsychiatrique des patients présentant un syndrome microdélétionnel 22q11.2 : du soin à la prévention.

22q11.2DS is one of the more frequent genetic syndromes associated to psychiatric symptoms. It has been associated to an increased risk to develop schizophrenia in adolescence or early adulthood. However, psychiatric symptoms appear early on, and should be recognized as soon as possible by child psychiatrists in order to improve the present well-being of children and their family, and to prevent further risks of developing severe and chronic psychiatric diseases later on. In this paper, we present a review of the recent literature concerning the 22q11.2DS syndrome focused on the risk factors that may be associated to an increased risk of psychotic transition. We advocate for the development of systematic specialized child psychiatry consultations for these patients, included in networks with geneticists, adult psychiatrists, and family associations, in order to improve their psychiatric prognosis and to support the development of translational research.

Consideraciones anestésicas en pacientes con microdeleción del cromosoma 22q11 / Anesthetic issues in patients mycrodeletion syndrome produced by the deletion of chromosome 22q11

The syndrome produced by the deletion of chromosome 22q11 corresponds to a pattern of anomalies that occurs when a specific region of chromosome 22 is lost, specifically called 22q11.2. This microdeletion corresponds to the most frequent chromosomal alteration in humans, which has a prevalence of 1 per 4,000 live births. This includes a great variety of phenotypes, many of them subclinical, among which the Di George syndrome and the Velocardiofacial syndrome stand out. The main cause of mortality is of cardiac origin. Embryologically, this microdeletion is associated with alterations in the differentiation and migration of the pharyngeal system, with consequent craniofacial, cardiac, airway, thymus and parathyroid alterations, among others. In this sense, these patients present a higher risk of complications such as inmunodeficiency, hypocalcemia and hemorrhagic risk. From the surgical and anesthetic point of view, they can present cardiopathies of greater complexity of correction, which in some cases is also related to anatomical airway alterations which can constitute an important challenge when operating this type of patients. Considering the above, there is an increase in perioperative risk which could increase mortality. The objective of this review is to present the characteristics and behavior of this group of patients in the correction of their heart diseases, so that they are known by the anesthesiologists who work in the cardiovascular area.

El síndrome de microdeleción 22q11 corresponde a un patrón de anomalías que se produce al perderse una región específica del cromosoma 22, específicamente llamada 22q11.2. Esta microdeleción corresponde a la alteración genética más frecuente en humanos la cual tiene una prevalencia de 1 cada 4.000 recién nacidos vivos. Incluye una gran variedad de fenotipos, muchos de ellos subclínicos, entre los que destaca el síndrome Di George y el síndrome Velocardiofacial. La principal causa de mortalidad es de origen cardíaco. Embriológicamente la microdeleción se asocia a alteraciones en diferenciación y migración del aparato faríngeo, con las consiguientes alteraciones cráneo-faciales, cardíacas, de vía aérea, timo y paratiroides, entre otras. En ese sentido, presentan mayor frecuencia de complicaciones tales como infecciones, hipocalcemia y riesgo hemorrágico. Desde el punto de vista quirúrgico y anestésico pueden presentar cardiopatías de mayor complejidad de corrección, asociado o no a alteraciones anatómicas en vía aérea lo que puede constituir un importante desafío al momento de intervenir. Lo anterior aumenta el riesgo perioperatorio, lo que podría derivar en aumento de la mortalidad. El objetivo de esta revisión es presentar las características y comportamiento de este grupo de pacientes en la corrección de sus cardiopatías, de modo que sean un aporte para los anestesiólogos que se desempeñan en el área cardiovascular.

Prenatal diagnosis and clinical implications of an apparently isolated right aortic arch.

OBJECTIVE: To define the associations of a prenatally diagnosed, apparently isolated right aortic arch (RAA) with chromosomal or genetic abnormalities and tracheal compression. METHODS: This was a retrospective study of apparently isolated RAA assessed by fetal cardiologists and fetal medicine specialists at Kings College Hospital, London between 2000 and 2017. RESULTS: The search identified 138 cases of apparently isolated RAA. Invasive testing was performed in 75, and chromosomal or genetic anomalies were identified in 16 (22%), and the most common was 22q11 microdeletion. An aberrant left subclavian artery was seen in 51% of cases. Symptoms of a vascular ring were present in 24 of 97 (25%) children who were reviewed after birth. Bronchoscopy was performed in 33 children, and significant tracheal compression was diagnosed in 28, including 18 of 19 symptomatic and 10 of 14 asymptomatic children. CONCLUSIONS: An apparently isolated RAA is associated with a high incidence of chromosomal or genetic abnormalities and a high incidence of tracheal compression in symptomatic and asymptomatic patients. Prenatal counselling for genetic associations and postnatal airway assessment in the context of the vascular anatomy is recommended.

Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a mouse model of schizophrenia.

Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioral traits that are relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. We studied an animal model of the human 22q11 deletion syndrome, the mutation that represents the highest genetic risk of developing schizophrenia. We observed a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches was sufficient to restore wild-type-like CA1 network dynamics and hippocampal-dependent behavior during adulthood. In conclusion, our data provide insights into the network dysfunction underlying schizophrenia and highlight the use of reverse engineering to restore physiological and behavioral phenotypes in an animal model of neurodevelopmental disorder.