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Journal of Clinical Psychopharmacology22q11.2 deletion syndrome confers significant risk for the development of schizophrenia. While current recommendations regarding the management of psychotic symptoms in...
BACKGROUND
22q11.2 deletion syndrome confers significant risk for the development of schizophrenia. While current recommendations regarding the management of psychotic symptoms in affected individuals are generally in keeping with treatment guidelines for general schizophrenia populations, evidence for the use of clozapine has come from case reports and retrospective observational data. As no reviews on the topic currently exist, a systematic review of clozapine use in 22q11.2 deletion syndrome was completed.
METHODS
In November 2023, a literature search was completed using both PubMed and Scopus to identify English-language articles that reported the use of clozapine in humans with 22q11.2 deletion syndrome.
RESULTS
Twenty-six articles describing 57 individuals were deemed eligible for inclusion. Most individuals had a diagnosis of treatment-resistant schizophrenia. Where reported, the mean or median dose of clozapine was relatively low, and the majority of individuals exhibited a good response (approximately 65.5% across individual case reports/series). While seizures were unsurprisingly the most commonly reported serious adverse effect, the majority of individuals were able to remain on (or be restarted on) clozapine by having their dose decreased and/or by adding an anticonvulsant (most commonly valproate).
CONCLUSIONS
This review reaffirms that individuals with 22q11.2 deletion syndrome may benefit from clozapine therapy even at a low dose, assuming they meet criteria for treatment-resistant schizophrenia and provided no contraindications exist. However, given the increased incidence of seizures in 22q11.2 deletion syndrome, the use of prophylactic anticonvulsant therapy should be considered, and hypoparathyroidism/hypocalcemia screened for and corrected before the initiation of clozapine. It is also recommended that clozapine blood levels be monitored.
Topics: Humans; Clozapine; DiGeorge Syndrome; Antipsychotic Agents; Anticonvulsants; Retrospective Studies; Seizures
PubMed: 38407281
DOI: 10.1097/JCP.0000000000001816 -
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 -
The Journal of Craniofacial Surgery Oct 2023The purpose of this study was to examine and compare surgical and speech outcomes of the posterior pharyngeal flap and sphincter pharyngoplasty following surgical... (Meta-Analysis)
Meta-Analysis
Pharyngeal Flap Versus Sphincter Pharyngoplasty for the Treatment of Velopharyngeal Insufficiency in 22q11.2 Deletion Syndrome: Preliminary Findings From a Systematic Review.
The purpose of this study was to examine and compare surgical and speech outcomes of the posterior pharyngeal flap and sphincter pharyngoplasty following surgical management of velopharyngeal insufficiency in patients with 22q11.2 deletion syndrome (22q11.2DS). This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses checklist and guidelines. Selected studies were chosen using a 3-step screening process. The 2 primary outcomes of interest were speech improvement and surgical complications. Preliminary findings based on included studies suggest a slightly higher rate of postoperative complications with the posterior pharyngeal flap in patients with 22q11.2DS but a lower percentage of patients needing additional surgery compared with the sphincter pharyngoplasty group. The most reported postoperative complication was obstructive sleep apnea. Results from this study provide some insight into speech and surgical outcomes following pharyngeal flap and sphincter pharyngoplasty in patients with 22q11.2DS. However, these results should be interpreted with caution due to inconsistencies in speech methodology and lack of detail regarding surgical technique in the current literature. There is a significant need for standardization of speech assessments and outcomes to help optimize surgical management of velopharyngeal insufficiency in individuals with 22q11.2DS.
Topics: Humans; Velopharyngeal Insufficiency; DiGeorge Syndrome; Pharynx; Plastic Surgery Procedures; Speech; Postoperative Complications; Treatment Outcome; Retrospective Studies; Cleft Palate
PubMed: 37431935
DOI: 10.1097/SCS.0000000000009531 -
Clinical and Experimental Rheumatology Apr 2024To describe the phenotypic, genetic, and outcome characteristics of large-vessel vasculopathy (LVV) in childhood associated with genetic variants. Additionally, a...
OBJECTIVES
To describe the phenotypic, genetic, and outcome characteristics of large-vessel vasculopathy (LVV) in childhood associated with genetic variants. Additionally, a systematic literature review was conducted to delineate the differences between LVV with and without genetic variants.
METHODS
The medical records of all children with LVV seen between January 2000 and September 2022 at our institution were retrospectively reviewed for demographic, clinical and genetic data, and outcomes at the last follow-up visit. In addition, we systematically reviewed the literature for the clinical features and known variants of previously reported cases.
RESULTS
Eleven patients with childhood LVV were identified; five (three males) of them had proven genetic variants (two DOCK8variants, one FOXP3, one DiGeorge syndrome, and one ZNF469 variant), while six patients had sporadic childhood LVV. Remarkably, patients with genetic variants were younger and had early-onset disease. However, the diagnosis of LVV was delayed compared to those without genetic variants. All patients with genetic variants were treated with corticosteroids, and three patients required sequential immunosuppressive drugs. Four patients underwent surgical intervention, and one received a haematopoietic stem-cell transplant (HSCT). Three patients achieved clinical remission, and two died. Furthermore, data from 20 previously published cases was extracted from the literature. All patients had inherited disorders. Of those, 14 patients had a genetically proven diagnosis. Most of them are treated with corticosteroids and immunosuppressive drugs, with partial responses. Two patients underwent HSCT. There were four deaths.
CONCLUSIONS
This study demonstrates that a variety of inherited disorders may contribute to childhood LVV. Strong genetic evidence and the preponderance of autosomal-recessive inheritance may allow us to propose that monogenic LVV is a distinct entity.
Topics: Humans; Phenotype; Male; Child; Female; Child, Preschool; Genetic Predisposition to Disease; Adolescent; Immunosuppressive Agents; Genetic Variation; Retrospective Studies; Infant; Treatment Outcome; Risk Factors; Adrenal Cortex Hormones; Vascular Diseases; Age of Onset; Forkhead Transcription Factors; Hematopoietic Stem Cell Transplantation; Guanine Nucleotide Exchange Factors; DNA-Binding Proteins
PubMed: 37404170
DOI: 10.55563/clinexprheumatol/je8rq2