PDD-NOS, psychotic features and executive function deficits in a boy with proximal 22q11.2 microduplication: Evolution of the psychiatric symptom profile from childhood to adolescence

Woestelandt, Laure; Novo, Alexandre; Philippe, Anne; Guyaux, N.; Rio, Marlène; Romano, Steven J.; Robel, Laurence

doi:10.1016/j.ejmg.2018.01.003

Cited by 5 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice that overexpress a segment of 22q11.2 are normal, a finding in accordance with the observation that duplication of 22q11.2 does not increase the risk for schizophrenia and rather might be a protective factor for schizophrenia (but see also van Amelsvoort et al . and Woestelandt et al …”

Section: Rdoc Domain Constructs In Mouse Models Of Cnvsupporting

confidence: 86%

Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models

Hiroi

2018

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Copy number variants are deletions and duplications of a few thousand to million base pairs and are associated with extraordinarily high levels of autism spectrum disorder, schizophrenia, intellectual disability, or attention-deficit hyperactivity disorder. The unprecedented levels of robust and reproducible penetrance of copy number variants make them one of the most promising and reliable entry points to delve into the mechanistic bases of many mental disorders. However, the precise mechanistic bases of these associations still remain elusive in humans due to the many genes encoded in each copy number variant and the diverse associated phenotypic features. Genetically engineered mice have provided a technical means to ascertain precise genetic mechanisms of association between copy number variants and dimensional aspects of mental illnesses. Molecular, cellular, and neuronal phenotypes can be detected as potential mechanistic substrates for various behavioral constructs of mental illnesses. However, mouse models come with many technical pitfalls. Genetic background is not well controlled in many mouse models, leading to rather obvious interpretative issues. Dose alterations of many copy number variants and single genes within copy number variants result in some molecular, cellular, and neuronal phenotypes without a behavioral phenotype or with a behavioral phenotype opposite to what is seen in humans. In this review, I discuss technical and interpretative pitfalls of mouse models of copy number variants and highlight well-controlled studies to suggest potential neuronal mechanisms of dimensional aspects of mental illnesses. Mouse models of copy number variants represent toeholds to achieve a better understanding of the mechanistic bases of dimensions of neuropsychiatric disorders and thus for development of mechanism-based therapeutic options in humans.

show abstract

Section: Rdoc Domain Constructs In Mouse Models Of Cnvsupporting

confidence: 86%

Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models

Hiroi

2018

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

show abstract

“…13 We detected the "22q11.2 duplication syndrome" (MIM#608363), a disorder with a highly variable expressivity and incomplete penetrance, that has been related to autism spectrum disorder 14 and ADHD. 15 Our patient met the criteria for both autism spectrum disorder and global developmental delay; moreover, her behavior was characterized by motor instability and attention weakness, though not meeting criteria for a diagnosis of ADHD.…”

Section: Discussionmentioning

confidence: 75%

A Not So Benign Family Pedigree With Hereditary Chorea: A Broader Phenotypic Expression or Additional Picture?

Milone

Masson

Cosmo

et al. 2019

Child Neurology Open

View full text Add to dashboard Cite

NKX2-1 mutations have been usually associated with a non-progressive neurological disease. Recent reports revealed a vast variability regarding its clinical expressivity. Aim of this work was widening the Benign Hereditary Chorea neurological, cognitive and behavioral phenotype through the description of a child and her family pedigree. Molecular analysis focused on NKX2-1 gene revealed a novel frameshift mutation in the three-generation members described. Cognitive scales detected a relevant developmental delay, and the clinical observation and Autism Diagnostic Observation Schedule -2 administration allowed the diagnosis of autism spectrum disorder in the proband. Microarray testing, further executed to exclude a double hit contextually provoking the complex neurodevelopmental disorder, revealed the 22q11.2 Duplication Syndrome. This paper may contribute to enlarge Benign Hereditary Chorea variable expressivity and, together with other studies reported in the literature, underlines the need to reconsider the term “benign,” verifying the opportunity of more a complex diagnosis.

show abstract

“…Cases of full remission were reported with aripiprazole 8 mg (Kontoangelos et al, 2020), risperidone 3 mg (Tastuzawa et al, 2015), quetiapine 200 mg (Kontoangelos et al, 2015), olanzapine 5 mg (Molebatsi and Olashore, 2018) and with a combination of lithium and olanzapine (Duarte et al, 2017). Interestingly, some cases reported complete remission of psychosis after withdrawing the antipsychotic following adverse events (Kim et al, 2020; Woestelandt et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

The effectiveness and tolerability of pharmacotherapy for psychosis in 22q11.2 Deletion Syndrome: A systematic review

Tanham,

Chen,

Warren

et al. 2024

Aust N Z J Psychiatry

View full text Add to dashboard Cite

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.

show abstract

PDD-NOS, psychotic features and executive function deficits in a boy with proximal 22q11.2 microduplication: Evolution of the psychiatric symptom profile from childhood to adolescence

Cited by 5 publications

References 23 publications

Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models

Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models

A Not So Benign Family Pedigree With Hereditary Chorea: A Broader Phenotypic Expression or Additional Picture?

The effectiveness and tolerability of pharmacotherapy for psychosis in 22q11.2 Deletion Syndrome: A systematic review

Contact Info

Product

Resources

About