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American Journal of Medical Genetics.... Oct 2018The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide...
The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide phenotypic variability, including orthopaedic manifestations. The purpose of this systematic review is to increase the awareness of orthopaedic manifestations associated with 22q11.2DS. This systematic review was performed according to the PRISMA Guidelines. Original epidemiological studies on the prevalence of orthopaedic manifestations within 22q11.2DS were systematically searched for in PubMed and EMBASE. The included articles were scored according to a risk-of-bias tool, a best-evidence synthesis was performed and the prevalence data was extracted. Sixty-nine published manuscripts described 58 orthopaedic manifestations in a total of 6,055 patients. The prevalence of at least one cervical or occipital anomaly is 90.5-100% (strong evidence). Fourteen studies (n = 2,264) revealed moderate evidence for a wide scoliosis prevalence of 0.6-60%. Two studies demonstrated that 5-6.4% of all 22q11.2DS patients required surgical scoliosis correction. Fifteen studies (n = 2,115) reported a 1.1-13.3% prevalence of clubfoot with moderate evidence. Other reported orthopaedic manifestations are patellar dislocation (10-20%), juvenile rheumatic arthritis (3.75%), impaired growth and skeletal anomalies like polydactyly (1.0-3.7%), syndactyly (11-11.8%), butterfly vertebrae (11.1%) and 13 ribs (2-19%). Orthopaedic findings are important manifestations of the 22q11.2DS, both in bringing patients to diagnostic attention and in requiring surveillance and appropriate intervention. Data on these manifestations are scattered and incomprehensive. Routinely screening for cervical anomalies, scoliosis, and upper and lower limb malformations is recommended in this vulnerable group of patients.
Topics: Awareness; Bone Diseases; DiGeorge Syndrome; Humans; Prevalence
PubMed: 29159873
DOI: 10.1002/ajmg.a.38545 -
Frontiers in Pediatrics 2021Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific...
Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific genetic syndromes associated with a risk of autoimmune disorders. We aimed to systematically evaluate the prevalence of IBD in specific genetic syndromes and to review the clinical characteristics of the published cases. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies describing patients with IBD and a genetic syndrome and/or studies indicating the prevalence or incidence of IBD in subjects with a genetic syndrome were included. Forty-six studies describing a total of 67 cases of IBD in six genetic syndromes and two personally assessed unpublished cases were included in the review. The majority of cases were associated with Turner syndrome (TS) (38 cases), Down syndrome (DS) (18 cases) and neurofibromatosis type 1 (NF1) (8 cases). Sporadic cases were described in DiGeorge syndrome (2), Kabuki syndrome (2), and Williams syndrome (1). The prevalence of IBD ranged from 0.67 to 4% in TS and from 0.2 to 1.57% in DS. The incidence of IBD was increased in TS and DS compared to the general population. Eight cases of IBD in TS had a severe/lethal course, many of which described before the year 2000. Two IBD cases in DS were particularly severe. Evidence of a greater prevalence of IBD is accumulating in TS, DS, and NF1. Management of IBD in patients with these genetic conditions should consider the presence of comorbidities and possible drug toxicities. : PROSPERO, identifier: CRD42021249820.
PubMed: 34765575
DOI: 10.3389/fped.2021.742830 -
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 -
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 -
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 -
Journal of the Medical Association of... Aug 2016The prevalence of 22q11.2 deletion in patients presenting with isolated cleft palate has not been systematically assessed. (Review)
Review
BACKGROUND
The prevalence of 22q11.2 deletion in patients presenting with isolated cleft palate has not been systematically assessed.
OBJECTIVE
To assess the evidence in the literature for the prevalence of 22q11.2 deletion in patients who were presenting with isolated cleft palate.
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 cleft palate.
RESULTS
Of the six prospective studies reported, 328 patients with isolated cleft palate had been screened with FISH (Fluorescence In Situ Hybridization) test for 22q11.2 deletion. Among the 328 patients, there was one (0.3%) patient with positive FISH test for 22q11.2 deletion. This patient was clinically assessed and did not have an associated malformation or clinically recognized syndrome.
CONCLUSION
The prevalence of 22q11.2 deletion among patients with isolated cleft palate is rather low. Of more than 400 genetic disorders involving occurrences of isolated cleft palate, FISH testing for 22q11.2 deletion in a patient with isolated cleft palate is recommended on clinical suspicion of additional clinical presentations of 22q11.2 deletion syndrome such as conotruncal congenital heart diseases, dysmorphic facies, velopharyngeal insufficiencies, immune deficiencies, hypoparathyroidisms, and neuropsychiatric disorders.
Topics: Cleft Palate; DiGeorge Syndrome; Humans; In Situ Hybridization, Fluorescence; Prevalence; Prospective Studies
PubMed: 29906081
DOI: No ID Found -
American Journal of Medical Genetics.... Aug 2022Crossed pulmonary arteries (CPAs) represent an uncommon anatomic variant, usually associated with some specific syndromes and conotruncal defects. This finding has been... (Review)
Review
Crossed pulmonary arteries: An underestimated cardiovascular variant with a strong association with genetic syndromes-A report of 74 cases with systematic review of the literature.
Crossed pulmonary arteries (CPAs) represent an uncommon anatomic variant, usually associated with some specific syndromes and conotruncal defects. This finding has been described in 22q11.2 Deletion Syndrome (22q11.2DS). We evaluated the correlation between CPAs and genetic diseases, in order to better define the characteristics of this variant, considered a rare anatomic pattern. An in-depth analysis of CPAs genotype-phenotype correlations was performed via a literature review. We detected 74 CPAs patients through echocardiography. Of these 74 patients, 35.1% of patients showed additional intracardiac malformations, while 29.7% showed extracardiac vascular anomalies, of which 16.2% were associated with intracardiac defects and 13.5% were not. In all, 62.2% of patients were diagnosed with genetic diseases and 52.2% of them were 22q11.2DS patients. In conclusions, CPAs represent a cardiovascular variant, which is detectable in nonsyndromic individuals, but especially in various genetic syndromes and in particular in 22q11.2DS patients. Data on the real prevalence of this morphology is lacking in literature. Knowledge of this anatomic variant is useful to interpret the unusual course of the pulmonary branches and is helpful information before cardiovascular surgical correction. Moreover, due to the strong association of CPAs with some genetic syndromes, the identification of this anatomic pattern can indicate the utility of a genetic assessment of these patients.
Topics: Chromosome Deletion; Chromosomes, Human, Pair 22; DiGeorge Syndrome; Heart Defects, Congenital; Humans; Lung; Pulmonary Artery
PubMed: 35491976
DOI: 10.1002/ajmg.a.62763 -
American Journal of Medical Genetics.... Nov 2019The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition and the most prevalent microdeletion syndrome in humans. Approximately 25% of individuals with... (Meta-Analysis)
Meta-Analysis
The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition and the most prevalent microdeletion syndrome in humans. Approximately 25% of individuals with 22q11.2DS receive antipsychotic treatment. To assess whether patients with 22q11.2DS are vulnerable to adverse effects of antipsychotic medication, we carried out a literature review. A systematic search strategy was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Publications describing adverse effects of antipsychotic medication in patients with 22q11.2DS were included in the review and assessed for their methodological quality. A total of 11 publications reporting on eight trials, cross-sectional or cohort studies, and 30 case reports were included. The most commonly reported adverse effects can be classified into the following categories: movement disorders, weight gain, seizures, cardiac side effects, and cytopenias. Many of these symptoms are manifestations of 22q11.2DS, also in the absence of antipsychotic medication. Based on the reviewed literature, a causal relation between antipsychotic medication and the reported adverse effects could not be established in the majority of cases. Randomized clinical trials are needed to make firm conclusions regarding risk of adverse effects of antipsychotics in patients with 22q11.2DS.
Topics: Antipsychotic Agents; DiGeorge Syndrome; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Humans; Phenotype
PubMed: 31407842
DOI: 10.1002/ajmg.a.61324 -
The Journal of Craniofacial Surgery Jul 2017The majority of patients with 22q11.2 deletion syndrome suffer from velopharyngeal insufficiency (VPI). Patients with 22q11.2 deletion syndrome (22qDS) commonly present... (Review)
Review
INTRODUCTION
The majority of patients with 22q11.2 deletion syndrome suffer from velopharyngeal insufficiency (VPI). Patients with 22q11.2 deletion syndrome (22qDS) commonly present with a large central velopharyngeal gap in the setting of poor velar and pharyngeal wall motion. The posterior pharyngeal flap is considered the most effective technique to treat VPI in this complex patient group. This study aims to critically evaluate success rates of surgical management of VPI in 22qDS patients and discuss options for management of a failed posterior pharyngeal flap (PPF) with persistent VPI.
METHODS
A systematic review was performed through MEDLINE and Scopus to examine the outcomes of PPF surgery to treat VPI in patients with 22qDS. Complications were defined as persistent VPI, hyponasal speech, and obstructive sleep apnea. To demonstrate an approach to management, the authors outline a recent patient with a failed PPF in this patient population at the authors' institution.
RESULTS
The authors comprehensively reviewed 58 articles, 13 of which contained relevant information with extractable data. Of the 159 patients with 22qDS who underwent PPF to treat VPI, successful outcomes were reported in 135 patients (80%; range: 0%-100%). Complications were reported in 14% of patients, with need for revision operations in 3%.
DISCUSSION
Surgical management of VPI in patients with 22qDS is challenging, with variable success rates reported in the literature. If unsuccessful, the surgeon faces additional challenges with the revision surgery including a scarred PPF donor site, distorted palatal recipient site, and further medialization of internal carotid arteries. Surgical revision of a failed PPF requires meticulous preoperative planning and technical execution.
Topics: Child; DiGeorge Syndrome; Humans; Male; Pharynx; Postoperative Complications; Sleep Apnea, Obstructive; Speech; Surgical Flaps; Treatment Outcome; Velopharyngeal Insufficiency
PubMed: 28582304
DOI: 10.1097/SCS.0000000000003722 -
Pediatric Cardiology Aug 2019Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and... (Meta-Analysis)
Meta-Analysis
Tetralogy of Fallot (ToF) is one of the most common cyanotic congenital heart defects. We sought to summarize all available data regarding the epidemiology and perioperative outcomes of syndromic ToF patients. A PRISMA-compliant systematic literature review of PubMed and Cochrane Library was performed. Twelve original studies were included. The incidence of syndromic ToF was 15.3% (n = 549/3597). The most prevalent genetic syndromes were 22q11.2 deletion (47.8%; 95% CI 43.4-52.2) and trisomy 21 (41.9%; 95% CI 37.7-46.3). Complete surgical repair was performed in 75.2% of the patients (n = 161/214; 95% CI 69.0-80.1) and staged repair in 24.8% (n = 53/214; 95 CI 19.4-30.9). Relief of RVOT obstruction was performed with transannular patch in 64.7% (n = 79/122; 95% CI 55.9-72.7) of the patients, pulmonary valve-sparing technique in 17.2% (n = 21/122; 95% CI 11.5-24.9), and RV-PA conduit in 18.0% (n = 22/122; 95% CI 12.1-25.9). Pleural effusions were the most common postoperative complications (n = 28/549; 5.1%; 95% CI 3.5-7.3). Reoperations were performed in 4.4% (n = 24/549; 95% CI 2.9-6.4) of the patients. All-cause mortality rate was 9.8% (n = 51/521; 95% CI 7.5-12.7). Genetic syndromes are seen in approximately 15% of ToF patients. Long-term survival exceeds 90%, suggesting that surgical management should be dictated by anatomy regardless of genetics.
Topics: Cardiac Surgical Procedures; DiGeorge Syndrome; Down Syndrome; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Postoperative Complications; Pulmonary Valve; Reoperation; Retrospective Studies; Tetralogy of Fallot; Treatment Outcome
PubMed: 31214731
DOI: 10.1007/s00246-019-02133-z