Young adults with a 22q11.2 microdeletion and the cost of aging with complexity in a population-based context.

PURPOSE: Information about the impact on the adult health care system is limited for complex rare pediatric diseases, despite their increasing collective prevalence that has paralleled advances in clinical care of children. Within a population-based health care context, we examined costs and multimorbidity in adults with an exemplar of contemporary genetic diagnostics. METHODS: We estimated direct health care costs over an 18-year period for adults with molecularly confirmed 22q11.2 microdeletion (cases) and matched controls (total 60,459 person-years of data) by linking the case cohort to health administrative data for the Ontario population (∼15 million people). We used linear regression to compare the relative ratio (RR) of costs and to identify baseline predictors of higher costs. RESULTS: Total adult (age ≥ 18) health care costs were significantly higher for cases compared with population-based (RR 8.5, 95% CI 6.5-11.1) controls, and involved all health care sectors. At study end, when median age was <30 years, case costs were comparable to population-based individuals aged 72 years, likelihood of being within the top 1st percentile of health care costs for the entire (any age) population was significantly greater for cases than controls (odds ratio [OR], for adults 17.90, 95% CI 7.43-43.14), and just 8 (2.19%) cases had a multimorbidity score of zero (vs 1483 (40.63%) controls). The 22q11.2 microdeletion was a significant predictor of higher overall health care costs after adjustment for baseline variables (RR 6.9, 95% CI 4.6-10.5). CONCLUSION: The findings support the possible extension of integrative models of complex care used in pediatrics to adult medicine and the potential value of genetic diagnostics in adult clinical medicine.

Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants.

BACKGROUND: The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis. METHOD: One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS). RESULTS: The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05). CONCLUSION: Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Childhood manifestations of 22q11.2 deletion syndrome: A Finnish nationwide register-based cohort study.

AIM: The aim of the study was to describe the clinical manifestations of 22q11.2 deletion syndrome patients in the Finnish paediatric population. METHODS: Nationwide registry data including all diagnoses and procedures of every public hospital in Finland between 2004 and 2018 along with mortality and cancer registry data were retrieved. Patients born during the study period and with an ICD-10 code of D82.1 or Q87.06 were included as having 22q11.2 deletion syndrome. A control group was formed with patients born during the study period and with benign cardiac murmur diagnosed under the age of 1 year. RESULTS: We identified 100 pediatric patients with 22q11.2 deletion syndrome (54% males, median age at diagnosis <1 year, median follow-up 9 years). Cumulative mortality was 7.1%. Among patients with 22q11.2 deletion syndrome, 73.8% had congenital heart defects, 21.8% had cleft palate, 13.6% had hypocalcaemia, and 7.2% had immunodeficiencies. Furthermore, 29.6% were diagnosed with autoimmune diseases, 92.9% had infections, and 93.2% had neuropsychiatric and developmental issues during follow-up. Malignancy was found in 2.1% of the patients. CONCLUSION: The 22q11.2 deletion syndrome is associated with increased mortality and substantial multimorbidity in children. A structured multidisciplinary approach is necessary for managing patients with 22q11.2 deletion syndrome.

Adaptive living skills, sleep problems, and mental health disorders in adults with 22q11.21 deletion syndrome.

BACKGROUND: 22q11.21 deletion syndrome (22q11DS) is a neurodevelopmental syndrome caused by a microdeletion of genes at the 22q11.21 locus. It has a prevalence of 1:2000. This study investigated the prevalence of adaptive living skills, sleep problems, and mental health disorders in adults with 22q11DS and examined the relationship between these factors. METHODS: Parents with an adult son or daughter with 22q11DS completed the following: A bespoke Demographic Information Questionnaire, Sleep Questionnaire (SQ-SP), Psychopathology in Autism Checklist (PAC), and Activities of Daily Living (ADL) scale. Descriptive statistics, correlations, and one-way between groups analysis of variance (ANOVA) were conducted. RESULTS: Mental health difficulties, sleep problems, and low levels of adaptive living skills are prevalent in adults with 22q11DS. Strong positive correlations were identified between sleep problems, depression, and anxiety subscale scores and moderate negative correlations between depression, psychosis, and activities of daily living skills. CONCLUSION: Adults with 22q11DS need screening and treatment for mental health and sleep problems.

Educational challenges for 22q11.2 deletion syndrome in Japan: Findings from a mixed methods survey.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear. METHOD: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted. RESULTS: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families. CONCLUSIONS: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone.

Airway anomalies in patients with 22q11.2 deletion syndrome: A scoping review.

OBJECTIVE: People with 22q11.2 deletion syndrome (22q11DS) can present with a wide variety of findings. Various airway anomalies have been described intermittently within this syndrome, but this feature has not been extensively investigated. Increased provider awareness of these findings may help guide clinical decision-making and improve overall patient outcomes. The objectives of this review are to identify the types of airway anomalies in 22q11DS and the prevalence of airway anomalies within symptomatic individuals. METHODS: PubMed/MEDLINE, Cochrane Library, and EMBASE databases were searched in February 2022 for all available articles. Search terms included those that described 22q11DS or one of its synonymous conditions AND those that described airway anatomy and anomalies. The term airway anomaly was defined as any structural aberration in the conductive airway from the oral or nasal vestibule region to the mainstem bronchus. Studies were screened by two authors. A review of references was conducted. Eligible manuscripts underwent full-text review for quality appraisal and data extraction. RESULTS: From a total of 909 unique manuscripts, 58 studies were selected, describing 328 people. The prevalence of airway anomaly diagnosis within symptomatic individuals ranged from 14% to 74%. Twenty-two unique airway anomalies were described. Laryngeal web was the most frequently described anomaly, followed by airway malacia and subglottic stenosis. Laryngeal web was 40% sensitive for suggesting a diagnosis of 22q11DS. Among affected individuals, as many as 46% had multiple concomitant airway anomalies. Aside from respiratory symptoms, other features that prompted airway evaluation included difficult intubation or failed extubation. CONCLUSION: The findings within this review support the notion that a wide variety of airway anomalies may be seen in people with 22q11DS and that these findings have been discovered frequently in those with airway symptoms. Providers should maintain a low threshold to perform an airway examination in those with 22q11DS, especially when airway symptoms are present.

Adult Height, 22q11.2 Deletion Extent, and Short Stature in 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) manifests as a wide range of medical conditions across a number of systems. Pediatric growth deficiency with some catch-up growth is reported, but there are few studies of final adult height. We aimed to investigate how final adult height in 22q11.2DS compared with general population norms, and to examine predictors of short stature in in a cohort of 397 adults with 22q11.2DS (aged 17.6-76.3 years) with confirmed typical 22q11.2 microdeletion (overlapping the LCR22A to LCR22B region). We defined short stature as <3rd percentile using population norms. For the subset (n = 314, 79.1%) with 22q11.2 deletion extent, we used a binomial logistic regression model to predict short stature in 22q11.2DS, accounting for effects of sex, age, ancestry, major congenital heart disease (CHD), moderate-to-severe intellectual disability (ID), and 22q11.2 deletion extent. Adult height in 22q11.2DS showed a normal distribution but with a shift to the left, compared with population norms. Those with short stature represented 22.7% of the 22q11.2DS sample, 7.6-fold greater than population expectations (p < 0.0001). In the regression model, moderate-to-severe ID, major CHD, and the common LCR22A-LCR22D (A-D) deletion were significant independent risk factors for short stature while accounting for other factors (model p = 0.0004). The results suggest that the 22q11.2 microdeletion has a significant effect on final adult height distribution, and on short stature with effects appearing to arise from reduced gene dosage involving both the proximal and distal sub-regions of the A-D region. Future studies involving larger sample sizes with proximal nested 22q11.2 deletions, longitudinal lifetime data, parental heights, and genotype data will be valuable.

Parent-Reported Social-Communicative Skills of Children with 22q11.2 Copy Number Variants and Siblings.

22q11.2 deletion (22q11.2DS) and 22q11.2 duplication (22q11.2Dup) confer risk for neurodevelopmental difficulties, but the characterization of speech-language and social skills in 22q11.2Dup is still limited. Therefore, this study aims to delineate social-communicative skills in school-aged children with 22q11.2Dup (n = 19) compared to their non-carrier siblings (n = 11) and age-matched children with 22q11.2DS (n = 19). Parents completed two standardized questionnaires: the Children's Communication Checklist (CCC-2), screening speech, language, and social skills, and the Social Responsiveness Scales (SRS-2), assessing deficits in social behavior. Parents report that both children with 22q11.2Dup and 22q11.2DS show more social-communicative deficits than the general population; children with 22q11.2Dup seem to take an intermediate position between their siblings and children with 22q11.2DS. Compared to 22q11.2DS, they demonstrate less frequent and less severe problems, and more heterogeneous social-communicative profiles, with fewer restricted interests and repetitive behaviors. In siblings of 22q11Dup, milder social-communicative difficulties and equally heterogeneous profiles are reported, which might indicate that-in addition to the duplication-other factors such as the broader genetic context play a role in social-communicative outcomes.

Characterization of Autoimmune Thyroid Disease in a Cohort of 73 Paediatric Patients Affected by 22q11.2 Deletion Syndrome: Longitudinal Single-Centre Study.

BACKGROUND: Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is the most frequent microdeletion syndrome and is mainly characterized by congenital cardiac defects, dysmorphic features, hypocalcemia, palatal dysfunction, developmental delay, and impaired immune function due to thymic hypoplasia or aplasia. Thyroid anomalies are frequently reported in patients with 22q11.2DS, although only a few well-structured longitudinal studies about autoimmune thyroid disease (ATD) have been reported. AIM: To longitudinally evaluate the frequency of thyroid anomalies and ATD in patients with 22q11.2DS. PATIENTS AND METHODS: Pediatric patients with a confirmed genetic diagnosis of 22q11.2DS were recruited and followed up on longitudinally. Clinical, biochemical, and immunological data were collected, as well as thyroid function, autoimmunity, and thyroid sonographic data. RESULTS: The study included 73 children with 22q11.2DS, with a mean follow-up duration of 9.51 ± 5.72 years. In all, 16 of the 73 enrolled patients (21.9%) developed ATD before 18 years of age (mean age 12.92 ± 3.66 years). A total of 20.5% developed Hashimoto's Thyroiditis (HT), of whom 50% required L-thyroxine treatment; 1.4% developed Graves Disease. Thyroid hypoplasia was found in 6/16 patients with ATD and left lobe hypoplasia in 9/16 patients. These features were also found in patients affected by 22q11.2DS without ATD. Among patients who developed ATD, at the first altered ultrasound scan, the most frequent anomalies suggestive of thyroiditis were inhomogeneous echotexture, diffuse or irregular hypo-echogenicity, and vascular overflow. CONCLUSION: We strongly recommend periodic screening of thyroid function and for autoimmunity in patients affected by 22q11.2DS. Along with blood tests, ultrasound scans of the thyroid gland should be performed periodically since some patients who go on to develop an ATD could have specific anomalies on ultrasound prior to any other anomaly.

Endocrine and Growth Disorders in Taiwanese Children With 22q11.2 Deletion Syndrome.

Background: Endocrine disorders are common in patients with 22q11.2 deletion syndrome (22q11.2DS). This study aimed to elucidate the clinical manifestations of endocrine disorders, including parathyroid, thyroid and growth disorders, in Taiwanese patients with 22q11.2DS. Methods: From 1994 to 2020, the medical records of 138 patients with 22q11.2DS diagnosed at a tertiary referral medical center in Taiwan were thoroughly reviewed retrospectively. Results: Hypocalcemia was detected in 57 of 135 patients (42%); 33 of 104 patients (32%) had hypoparathyroidism, and in 87% of them, hypocalcemia was detected before the age of one. Most patients had precipitating stressors during symptomatic hypocalcemic episodes. Eighteen of 29 patients had overt hypoparathyroidism at the last visit: 11 had persistent hypoparathyroidism and the other seven had recurrent hypoparathyroidism. Four of 84 patients had thyroid disorders, including thyroid developmental anomalies in two, dyshormonogenesis in one and Graves' disease in one. Fifty of 126 patients (40%) had short stature. Age (odds ratio (OR) 0.91; 95% confidence interval (CI) 0.86-0.96; P<0.001) and airway anomalies (OR 2.75; 95% CI 1.04-7.31; P<0.05) were significant risk factors for short stature in multivariate logistic regression model. Twenty-eight of the 30 patients with airway anomalies were associated with severe congenital heart disease. Adult height standard deviation score (SDS) in 19 patients was significantly lower than target height SDS (-1.15 ± 0.90 vs -0.08 ± 0.65, P<0.001). Conclusions: Hypoparathyroidism is a common endocrine disorder in patients with 22q11.2DS. It is prudent to assess parathyroid function at diagnosis and during follow-up, especially in the presence of stress, to prevent symptomatic hypocalcemia. Although thyroid disorders are not so common as hypoparathyroidism, screening of thyroid dysfunction is justified in these patients. Patients with 22q11.2DS demonstrate a retarded growth pattern with a tendency of catch-up and regular monitoring of growth is indicated.

Reflections of parents of children with 22q11.2 Deletion Syndrome on the experience of receiving psychiatric genetic counseling: 'Awareness to Act'.

Individuals with 22q11.2 deletion syndrome (22qDS) have a 25%-41% risk for a psychotic disorder. Although early intervention for psychiatric conditions leads to the best long-term outcomes, healthcare providers often provide inadequate information about these issues and psychiatric services are underused by this population. We conducted semi-structured interviews with parents of children with 22qDS a month after they received psychiatric genetic counseling (pGC), to evaluate outcomes and perceived value of pGC with respect to parents' needs. Using grounded theory, we generated a theoretical framework of the process of building parental awareness of psychiatric risks associated with 22qDS and protective and management strategies for mental health (MH). Parents described how after their child's diagnosis with 22qDS, a variety of barriers stalled their building awareness of psychiatric risk and protective/management strategies: dealing with the immediate symptoms of 22qDS; child's young age; parental fear and stigma; and missing MH guidance. These barriers led them to carry the burden of worrying over missing emerging psychiatric symptoms and the stress over advocating for their child's MH. Parents indicated pGC was beneficial in that led them to achieve an 'awareness to act,' feeling confident in being alert and equipped to protect and/or manage their child's MH.

Ocular findings in 22q11.2 deletion syndrome: A systematic literature review and results of a Dutch multicenter study.

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.

Blood brain barrier permeability increases with age in individuals with 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is characterised by high rates of psychotic disorders and immune abnormalities. Blood-brain barrier (BBB) permeability is known to be a risk factor for schizophrenia and immune aberrations. OBJECTIVE: To evaluate the relationship between psychosis and BBB permeability in this population. METHODS: We examined two biomarkers for BBB permeability, s100ß and neuron-specific enolase (NSE), in 22q11.2DS individuals with/without psychosis. The first cohort of this Israeli-Belgium study was comprised of 20 22q11.2DS adults (30.58 ± 9.42 years) afflicted with a psychotic disorder, another group of 69 non-psychotic 22q11.2DS adults (23.42 ± 8.36 years), and 58 healthy controls (26.39 ± 7.77 years). A second cohort was comprised of 18 non-psychotic 22q11.2DS Israeli children (5.83 ± 1.55 years) and 14 healthy controls (5.34 ± 1.43 years). NSE and s100ß serum levels were detected in all participants. RESULTS: Both factors were elevated in adults with 22q11.2DS compared to healthy controls, specifically in the non-psychotic sub-group. In contrast, there were no significant differences in their levels between the two groups of the paediatric cohort. CONCLUSIONS: Increased BBB permeability seems to be a trait of 22q11.2DS that evolves sometime in early adulthood. Our findings are in line with previous reports on non-syndromic schizophrenia, and suggest potential novel neural pathways to psychosis in 22q11.2DS.

Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan.

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (ß = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (ß = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (ß = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.

Prevalence and incidence of psychotic disorders in 22q11.2 deletion syndrome: a meta-analysis.

22q11.2 deletion syndrome (22q.11.2DS) might be one of the strongest genetic risk factors for psychosis, but robust estimates of prevalence and incidence of psychotic disorders in this condition are not available. To address this gap, we performed a multistep systematic PRISMA/MOOSE-compliant literature search of articles reporting prevalence (primary outcome) or incidence (secondary outcome) of psychotic disorders in 22q11.2DS samples (protocol: https://osf.io/w6hpg) using random-effects meta-analysis, subgroup analyses and meta-regressions. The pooled prevalence of psychotic disorders was 11.50% (95%CI:9.40-14.00%), largely schizophrenia (9.70%, 95%CI:6.50-14.20). Prevalence was significantly higher in samples with a mean age over 18 years, with both psychiatric and non-psychiatric comorbidities and recruited from healthcare services (compared to the community). Mean age was also significantly positively associated with prevalence in meta-regressions (p < 0.01). The pooled incidence of psychotic disorders was 10.60% (95%CI:6.60%-16.70%) at a mean follow-up time of 59.27 ± 40.55 months; meta-regressions were not significant. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prevalence and incidence of psychotic disorders in 22q11.2DS individuals. It demonstrates that around one in ten individuals with 22q11.2DS displays comorbid psychotic disorders, and around one in ten will develop psychosis in the following five years, indicating that preventive approaches should be implemented systematically in 22q11.2DS.

Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening.

BACKGROUND: Although pathogenic 22q11.2 deletions are an important cause of developmental delays and lifelong disease burden, their variable and complex clinical expression contributes to under-recognition, delayed molecular diagnosis and uncertainty about prevalence. We sought to estimate the contemporary live-birth prevalence of typical 22q11.2 deletions using a population-based newborn screening sample and to examine data available for associated clinical features. METHODS: Using DNA available from an unbiased sample of about 12% of all dried blood spots collected for newborn screening in Ontario between January 2017 and September 2018, we prospectively screened for 22q11.2 deletions using multiplex quantitative polymerase chain reaction assays and conducted independent confirmatory studies. We used cross-sectional analyses to compare available clinical and T-cell receptor excision circle (TREC, used in newborn screening for severe combined immunodeficiency) data between samples with and without 22q11.2 deletions. RESULTS: The estimated minimum prevalence of 22q11.2 deletions was 1 in 2148 (4.7 per 10 000) live births (95% confidence interval [CI] 2.5 to 7.8 per 10 000), based on a total of 30 074 samples screened, with 14 having confirmed 22q11.2 deletions. Of term singletons, samples with 22q11.2 deletions had significantly younger median maternal age (25.5 v. 32.0 yr, difference -6.5 yr, 95% CI -7 to -2 yr), a greater proportion with small birth weight for gestational age (odds ratio 7.00, 95% CI 2.36 to 23.18) and lower median TREC levels (108.9 v. 602.5 copies/3 µL, p < 0.001). INTERPRETATION: These results indicate that the 22q11.2 deletion syndrome is one of the most common of rare genetic conditions and may be associated with relatively younger maternal ages and with prenatal growth abnormalities. The findings support the public health importance of early - prenatal and neonatal - diagnosis that would enable prompt screening for and management of well-known actionable features associated with 22q11.2 deletions.

Riesgo de Esquizofrenia y Síndrome Deleción 22Q11. 2 / RIsk of schizophrenia and 22q11. 2 deletion syndrome

INTRODUCCIÓN. La deleción 22q11.2 es una alteración cromosómica muy frecuente, en la cual un 60% de los afectados presenta patologías neuropsiquiátricas. Determinar si existe asociación entre el síndrome de deleción 22q11.2 (SD22q11.2) y patologías como la esquizofrenia (EQZ), ofrece una oportunidad para la intervención temprana, y seguimiento de personas con este síndrome. OBJETIVO. El objetivo del presente trabajo es determinar si existe mayor riesgo de EQZ en pacientes con síndrome deleción 22q11.2. MÉTODOS. Se realizó una búsqueda bibliográfica sistemática de publicaciones con fecha de 1990 a 2020. Las búsquedas se realizaron en PubMed y en la base de datos Cochrane. En total, se evaluaron 19 estudios, de los que se consideraron elegibles diez publicaciones para el análisis, lo que corresponde a 824 participantes. RESULTADOS. El riesgo de presentar EQZ en un individuo con SD22q11.2 es de 20-25%, en comparación al 1% de la población general. CONCLUSIONES. El riesgo para un individuo con SD22q11.2 de presentar EQZ se encuentra bien establecido. Considerar este riesgo podría ayudar a un adecuado seguimiento y una intervención temprana.

INTRODUCTION. 22q11.2 deletion syndrome is a very common chromosomal abnormality, in which 60% of those affected have neuropsychiatric disorders. Determining if there is an association between 22q11.2 deletion syndrome (22q11.2DS) and disorders such as schizophrenia (SCZ) offers an opportunity for early intervention and follow-up of people with this syndrome. OBJECTIVE. The objective of this study is to determine if there is a greater risk of SCZ in patients with 22q11.2 deletion syndrome. METHODS. A systematic review was performed for publications dated 1990 to 2020. The strategy was to search in PubMed and Cochrane databases for specific MeSH terms. In total, 19 studies were reviewed, of which 10 publications were eligible for analysis, corresponding to 824 participants. RESULTS. The risk of presenting SCZ in an individual with 22q11.2DS is 20-25%, compared to 1% in the general population.CONCLUSIONS. The risk of presenting SCZ in an individual with 22q11.2DS is well established. Considering this risk could help with adequate follow-up and early intervention.

Primary immunodeficiency testing in a Massachusetts tertiary care NICU: persistent challenges in the extremely premature population.

BACKGROUND: Prematurity presents a diagnostic challenge in interpreting primary immunodeficiency (PID) testing. METHODS: We retrospectively reviewed the charts of all infants in our level IV referral neonatal intensive care unit (NICU) in Massachusetts, with immunologic testing performed from 2006 to 2018. RESULTS: The overall rate of PID testing was enriched in our population, with 1% of admitted patients having extended immunologic testing. The addition of TREC (T cell receptor excision circle) newborn screening in Massachusetts in 2009 increased the proportion of infants tested for PID in our NICU by 3-fold (1.21% post-newborn screening (NBS) vs. 0.46% pre-NBS). A majority of the term and late preterm (≥34 weeks) infants (31 of 41, 76%), as well as very premature (29-33 weeks) infants (12 of 17, 71%), who had immune testing, had a genetic diagnosis associated with secondary immunodeficiency or a PID. Most infants who were born extremely premature (EP, <29 weeks) (25 of 29, 86%) had no identifiable cause of immunodeficiency besides prematurity, despite a mean postmenstrual age of 40.1 weeks at the time of testing. CONCLUSIONS: Persistent immune derangements were present within a subgroup of the EP population through term postmenstrual age. EP infants with significant infectious history and abnormal immune testing at term-corrected age should be considered for genetic testing. IMPACT: The role of immunologic testing in the premature population is unclear, we therefore reviewed the records of all infants in our NICU who had immunologic testing, to rule out immunodeficiency, done from 2006 to 2018. The addition of newborn screening for SCID in 2009 doubled the number of infants who had immune investigations. The extremely premature cohort included many infants with persistent immune derangements through term-corrected gestational age, suggesting a persistent effect of prematurity on immune development and potential function. We propose that former premature infants with clinical evidence of immunodeficiency and sustained immune abnormalities by term-corrected age undergo genetic testing for immunodeficiency.

Medical and dental characteristics of children with chromosome 22q11.2 deletion syndrome at the Royal Children's Hospital, Melbourne.

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a multifaceted syndrome with a variable phenotype. Few studies have described the associated dental characteristics and their relationship with medical co-morbidities; and no Australian data exist. AIM: To determine the clinical manifestations and correlations between oral and medical conditions in children with 22q11.2DS. DESIGN: A retrospective observational study. Children genetically diagnosed with 22q11.2DS at the Royal Children's Hospital Melbourne were selected; their medical and dental characteristics were collated and analysed. RESULTS: The study population (n = 57; mean age 11.5 years, range 2-27 years) experienced a range of medical conditions involving multiple medical systems; of whom 44 (77.2%) had caries experience, 7 (12.3%) developmentally missing teeth, and 31 (54.4%) developmental defects of enamel (DDE). Smaller proportions of primary teeth were affected by DDE in children with congenital heart disease (2.2% vs 9.7%; P = .02), and cardiac surgery (0.2% vs 9%; P = .001). Conversely, children with hypoparathyroidism (n = 2) had significantly higher proportions of primary teeth affected by DDE (27.5% vs 4%; P = .02). CONCLUSIONS: Significant associations existed between medical conditions (congenital heart disease, history of cardiac surgery, and hypoparathyroidism) and primary dentition DDE in children with 22q11.2 DS.

Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.