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Children (Basel, Switzerland) Aug 202222q11.2 deletion syndrome (DS 22q11.2) is a rare disease of genetic origin, caused by the loss of the q11.2 region of chromosome 22. It affects one in 4000 live... (Review)
Review
22q11.2 deletion syndrome (DS 22q11.2) is a rare disease of genetic origin, caused by the loss of the q11.2 region of chromosome 22. It affects one in 4000 live newborns, and among the clinical manifestations that can occur in this syndrome are abnormalities in the parathyroid glands (producing calcium deficits), the palate, the heart and the thymus. It is also known as DiGeorge syndrome or velocardiofacial syndrome, among other names, depending on the clinical presentation of each individual. The main objective of the review was to update information on DS 22q11.2 from publications in the scientific literature. The daily activities of these patients are seriously impaired, due to the impact of the clinical manifestations. Interventions can be performed to improve their social, cognitive and emotional skills, thus increasing their ability to perform different daily activities.
PubMed: 36010058
DOI: 10.3390/children9081168 -
Genetics in Medicine : Official Journal... Mar 2023This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert...
This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.
Topics: Adult; Humans; Clinical Relevance; Consensus; DiGeorge Syndrome; Genetic Counseling; Surveys and Questionnaires
PubMed: 36729052
DOI: 10.1016/j.gim.2022.11.012 -
Orphanet Journal of Rare Diseases Aug 2019Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50-60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power.
RESULTS
Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (OR: 0.654 [0.408-1.046]; OR : 1.291 [0.860-1.939]) or palate anomalies (OR: 1.731 [0.708-4.234]; OR : 0.628 [0.286-1.382]).
CONCLUSIONS
The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes.
Topics: Arachnodactyly; Chromosome Deletion; Craniosynostoses; Humans; Marfan Syndrome; Phenotype
PubMed: 31399107
DOI: 10.1186/s13023-019-1170-x -
Journal of Developmental and Behavioral...22q11.2 deletion syndrome (22q11DS) is a common genetic deletion syndrome associated with psychiatric disorders and developmental delays. A significant amount of 22q11DS...
OBJECTIVE
22q11.2 deletion syndrome (22q11DS) is a common genetic deletion syndrome associated with psychiatric disorders and developmental delays. A significant amount of 22q11DS research literature is published annually; here, we focus exclusively on longitudinal data that have been published in the past 5 years regarding psychiatric disorders and/or cognitive and social development. After a review, areas for future research consideration and clinical recommendations are presented.
METHODS
Articles were reviewed and organized in adherence with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews. The literature search identified 852 studies, and 22 studies met inclusion criteria.
RESULTS
Longitudinal study findings indicate that developmental considerations for youth with 22q11DS should focus on the primacy and enduring nature of social and executive functioning deficits, attention-deficit/hyperactivity disorder, anxiety, and negative symptoms of psychosis.
CONCLUSION
From the diathesis of physiological conditions and genetic variance, 22q11DS and its associated phenotype of persistent cognitive deficits, comorbid psychiatric disorders, and social impairments likely conspire to increase the risk for stress in adolescence. The diathesis-stress framework, along with chronic stress, increases psychosis risk in individuals with 22q11DS. The existing literature has a heavy focus on the impact of the deletion on individual skills and attributes, such as cognition, but lacks information on the impact of the environment. Future 22q11DS research should consider specific aspects of social functioning, including interactions with parenting styles and family communication, as well as high demands in educational settings, as possible risk factors for psychosis.
Topics: Adolescent; Anxiety Disorders; Cognition; DiGeorge Syndrome; Humans; Longitudinal Studies; Psychotic Disorders
PubMed: 34110308
DOI: 10.1097/DBP.0000000000000927 -
The Australian and New Zealand Journal... May 2024The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans with over 180 phenotypic expressions. Approximately 30-40% of affected individuals... (Review)
Review
OBJECTIVE
The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans with over 180 phenotypic expressions. Approximately 30-40% of affected individuals will develop psychosis and 25% meet the criteria for schizophrenia. Despite this, pharmacotherapy for managing psychosis in 22q11.2DS is poorly understood and 22q11.2DS psychosis is frequently labelled as treatment resistant. The objectives of this paper are to evaluate the effectiveness and tolerability of pharmacotherapy for 22q11.2DS psychosis and evaluate the evidence for treatment resistance.
METHOD
A systematic search was performed using CINAHL, The Cochrane Library (Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials and Cochrane Clinical Answers), EMBASE, PsycINFO, PubMed, Scopus and Web of Science Core Collection from inception to December 2022. It yielded 39 case reports, 6 case series and 1 retrospective study which met the inclusion criteria.
RESULTS
Based on the current literature, individuals with 22q11.2DS psychosis experience a greater rate of medical co-morbidities such as cardiac arrhythmias, seizures and movement disorders, which complicate pharmacotherapy. Poor tolerability rather than poor clinical response motivates the switching of antipsychotics, which may explain the labelling of treatment resistance in the literature.
CONCLUSION
There are insufficient data to recommend a single antipsychotic for 22q11.2DS psychosis. Nonetheless, with proactive management of co-morbidities, antipsychotic medication in 22q11.2DS psychosis is an effective treatment commonly resulting in improvement in quality of life.
Topics: Humans; DiGeorge Syndrome; Psychotic Disorders; Antipsychotic Agents
PubMed: 38383990
DOI: 10.1177/00048674241233118 -
American Journal of Medical Genetics.... Feb 2022The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder with an estimated prevalence of 1:3000 live births. Manifestations show a marked variability in...
The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder with an estimated prevalence of 1:3000 live births. Manifestations show a marked variability in expression and include speech- and language delay, intellectual disability, and neuropsychiatric disorders. We aim to provide an overview of ocular findings in 22q11.2DS in order to optimize recommendations for ophthalmic screening. We combined results from a systematic literature review with results from a multicenter cross-sectional study of patients with 22q11.2DS who were assessed by an ophthalmologist. Our systematic literature search yielded four articles, describing 270 patients. We included 132 patients in our cross-sectional study (median age 8.9 [range 0-56] years). Most reported ocular findings were retinal vascular tortuosity (32%-78%), posterior embryotoxon (22%-50%), eye lid hooding (20%-67%), strabismus (12%-36%), amblyopia (2%-11%), ptosis (4%-6%), and refractive errors, of which hyperopia (6%-48%) and astigmatism (3%-23%) were most common. Visual acuity was (near) normal in most patients (91%-94%). Refractive errors, strabismus, and amblyopia are treatable conditions that are frequently present in patients with 22q11.2DS and should be corrected at an early stage. Therefore, in 22q11.2DS, we recommend ophthalmic and orthoptic screening at the age of 3 years or at diagnosis, and a low-threshold referral in adults.
Topics: Adolescent; Adult; Child; Child, Preschool; Cross-Sectional Studies; DiGeorge Syndrome; Eye Abnormalities; Humans; Infant; Infant, Newborn; Intellectual Disability; Language; Middle Aged; Multicenter Studies as Topic; Young Adult
PubMed: 34773366
DOI: 10.1002/ajmg.a.62556 -
Movement Disorders : Official Journal... Sep 2021The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic... (Review)
Review
The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic etiology. However, the link between parkinsonism or tremor and chromosome disorders, both numerical and structural, has been neglected. We reviewed the occurrence and characteristics of parkinsonism and tremor syndromes in patients with chromosomic disorders. We searched PubMed for articles published until December 2018, using the non-MESH terms "Chromosomopathy," "karyotype," "chromosome," "aneuploidy," "deletion," "inversion," "insertion," "duplication," and "Parkinson," "Parkinsonism," "Tremor," and "Parkinsonian disorder." We restricted the search to human studies and selected articles for further analysis after abstract review. Tremor syndromes in which patients had another possible clinical reason for syndromes were excluded, as well as tremor syndromes associated with point mutations, imprinting syndromes, and patients presenting with other hyperkinetic disorders. Fifty-four articles were reviewed. Aneuploidies of sex chromosomes were the most common chromosomopathy. These patients more commonly exhibited postural and kinetic tremor, often meeting the description of essential tremor. In structural chromosomopathies, the most frequent association was PD and 22q11.2 deletion syndrome, but we found case reports and case series of several additional deletion and duplication syndromes. © 2021 International Parkinson and Movement Disorder Society.
Topics: DiGeorge Syndrome; Essential Tremor; Humans; Parkinson Disease; Parkinsonian Disorders; Tremor
PubMed: 34056754
DOI: 10.1002/mds.28663 -
Journal of the Medical Association of... Aug 2016A birth prevalence of chromosome 22q11.2 deletion syndrome among population-based reports has been documented to vary, however, a systematic assessment is lacking. (Review)
Review
BACKGROUND
A birth prevalence of chromosome 22q11.2 deletion syndrome among population-based reports has been documented to vary, however, a systematic assessment is lacking.
OBJECTIVE
To assess the evidence in the literature for the birth prevalence of chromosome 22q11.2 deletion syndrome.
MATERIAL AND METHOD
A systematic literature search was conducted through PubMed between 1992 and June 2016 using search terms of 22q11.2 deletion OR 22q11 deletion and prevalence.
RESULTS
Of the six studies reported, there were 156 patients with 22q11.2 deletion syndrome found in total study populations of 1,111,336 live births. According to countries, the birth prevalence of this deletion syndrome (95% confidence interval) from United States, Belgium, Sweden, United Kingdom, France, and Singapore were 1.68 (1.22-2.26), 1.56 (1.33-1.72), 1.36 (0.91-2.08), 1.30 (0.45-2.15), 1.03 (0.53-2.23), and 1.02 per 10,000 live births, respectively. Estimates of minimum prevalence rates on the basis of the presence of this syndrome in cohorts of patients with cardiovascular malformations were from one in 4,000 to one in 7,092 live births.
CONCLUSION
This systematic review indicates that the 22q11.2 deletion syndrome is rather common. The findings can help physicians, health care planners and other health professionals to plan and manage better care of these patients.
Topics: DiGeorge Syndrome; Humans; Infant, Newborn; Live Birth; Prevalence
PubMed: 29906080
DOI: No ID Found -
European Child & Adolescent Psychiatry Aug 202022q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans and is associated with high rates of attention deficit/hyperactivity disorder (ADHD),...
22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans and is associated with high rates of attention deficit/hyperactivity disorder (ADHD), psychotic spectrum disorders and mood and anxiety disorders. The objective of the study was to systematically review studies regarding pharmacological treatments for psychiatric disorders in individuals with 22q11.2DS and to provide practical guidelines for the psychiatric management and side effect monitoring in 22q11.2DS. A literature search was conducted using the databases PubMed, PsycINFO and Embase. Information regarding study population, drug treatment, side effect profile and efficacy for each trial was extracted. Data collection was completed on May 2018. The search identified 705 studies. A total of seven studies, describing 182 individuals, were included. Pharmacological interventions included three studies for antipsychotic treatment, two studies for stimulants, one study for selective serotonin reuptake inhibitors (SSRIs), one study for S-adenosyl-L-methionine (SAMe), and one case series for metyrosine. The presented data support the clinical impression that individuals with 22q11.2DS and comorbid psychiatric disorders are treated in a manner comparable to non-22q11.2DS individuals. However, distinct medical comorbidities common in individuals with 22q11.2DS may complicate the administration of pharmacotherapy. Further trials with RCT design, larger sample sizes and more syndrome-specific pharmacological agents are needed to improve evidence-based psychiatric care of 22q11.2DS individuals with comorbid mental disorders.
Topics: Adolescent; Antipsychotic Agents; Comorbidity; DiGeorge Syndrome; Female; Humans; Male; Psychotic Disorders; Retrospective Studies
PubMed: 30949827
DOI: 10.1007/s00787-019-01326-4 -
Neuroscience and Biobehavioral Reviews Dec 201922q11.2 deletion syndrome (DS) is considered to be the most robust genetic model of psychosis. In the last decade, there has been increased interest in the brain... (Meta-Analysis)
Meta-Analysis
22q11.2 deletion syndrome (DS) is considered to be the most robust genetic model of psychosis. In the last decade, there has been increased interest in the brain abnormalities associated with these genetic changes. Most imaging findings in this population come from small samples. This increases the risk of reporting spurious effects that reflect the idiosyncrasies of each study. Thus, the current work is aimed at identifying whether there are spatially consistent structural and functional brain abnormalities in individuals with 22q11.2 DS through (i) a comprehensive label-based systematic review and (ii) a coordinate-based meta-analysis of magnetic resonance imaging studies. The systematic review identified the frontal middle gyri, posterior cingulum, right cuneus and bilateral precuneus as the most affected regions. The meta-analysis revealed consistent abnormalities in the bilateral inferior parietal lobe, right precuneus, right superior temporal gyrus and posterior cingulate cortex. This study provides an important starting point for future research as it sheds light on possible genetically determined psychosis susceptibility regions.
Topics: Brain; Brain Mapping; DiGeorge Syndrome; Humans; Magnetic Resonance Imaging; Nerve Net
PubMed: 31493414
DOI: 10.1016/j.neubiorev.2019.09.004