Access to Multidisciplinary Care for Patients With 22q11.2 Deletion Syndrome: Identifying Breakdowns in the Screening Process.

The 22q11.2 deletion syndrome affects approximately 1 in 4000 live births and involves cardiac defects, immunodeficiency, and endocrine disruption. The complexity of diagnosis and multifaceted care often leads to fragmented management in the short and long term. With the purpose of developing an effective multidisciplinary program, the authors aimed to identify the deficiencies in current screening and referral processes among the teams required in the care for patients with 22q11.2 deletion syndrome. A retrospective chart review was conducted at our institution between 2001 and 2016. Patients with confirmed 22q11.2 deletion diagnoses between the ages of 0 and 28 were included. A list of 15 relevant specialties that should evaluate patients with 22q11.2 deletion syndrome was created according to established guidelines. Patient medical and demographic information were collected and analyzed. A total of 270 patients were included. Mean age at diagnosis was 3.3 years. On average, patients visited 6 of 15 departments (1-14). Only 8.8% of patients visited >10 specialties. The majority were seen by Cardiology, Allergy and Immunology, Genetics, and Speech (57.4-87.8%). A minority were seen by Hematology and Oncology, Sleep Therapy, and Physical Therapy (13.3-16.3%). Only 34.1% encountered plastic surgery. Negative correlation (-0.128; P = 0.035) was demonstrated between patients' age at diagnosis and number of specialty teams encountered. This study highlights the current underutilization of services required to manage patients with 22q11.2 deletion syndrome. While screening guidelines have been established, implementation can be challenging as it requires efficient care coordination between teams. Moving forward, the authors believe that a multidisciplinary clinical approach to streamline patient care is necessary.

[Child psychiatry interventions in patients with 22q11 deletion syndrome: From treatment to prevention]. / Prise en charge pédopsychiatrique des patients présentant un syndrome microdélétionnel 22q11.2 : du soin à la prévention.

22q11.2DS is one of the more frequent genetic syndromes associated to psychiatric symptoms. It has been associated to an increased risk to develop schizophrenia in adolescence or early adulthood. However, psychiatric symptoms appear early on, and should be recognized as soon as possible by child psychiatrists in order to improve the present well-being of children and their family, and to prevent further risks of developing severe and chronic psychiatric diseases later on. In this paper, we present a review of the recent literature concerning the 22q11.2DS syndrome focused on the risk factors that may be associated to an increased risk of psychotic transition. We advocate for the development of systematic specialized child psychiatry consultations for these patients, included in networks with geneticists, adult psychiatrists, and family associations, in order to improve their psychiatric prognosis and to support the development of translational research.

Parkinson's disease associated with 22q11.2 deletion: Clinical characteristics and response to treatment.

BACKGROUND: While it is known that 22q11.2 microdeletions (22q11.2-del) increase the risk of Parkinson's disease (PD), the characteristics of PD associated with 22q11.2-del have not been specifically explored. OBJECTIVE: This report aimed to assess the clinical characteristics and treatment responses of PD patients with 22q11.2-del, and to describe any features that might lead neurologists to investigate the comorbidity. METHODS: Nine PD patients (eight men, one woman) with 22q11.2-del were followed at seven centers of the French PD Expert Network (Ns-Park). RESULTS: PD diagnosis was made before 22q11.2-del diagnosis in seven cases; their main characteristics were early onset (32-48 years) and good initial levodopa sensitivity, but with a course characterized by severe and early-onset levodopa-induced motor complications and psychiatric manifestations. Three patients received deep brain stimulation (DBS) that was effective. CONCLUSION: Searching for 22q11.2-del in PD patients presenting with suggestive features is relevant as the clinical presentation is similar to idiopathic PD, but with other associated characteristics, including a severe evolution. Results with DBS are similar to those reported for idiopathic PD.

The Effect of Loudness Variation on Velopharyngeal Function in Children with 22q11.2 Deletion Syndrome: A Pilot Study.

OBJECTIVE: Children with 22q11.2 deletion syndrome (22qDS) often require surgical intervention to treat velopharyngeal dysfunction (VPD). Although some studies have documented improved velopharyngeal (VP) closure under increased speaking effort, currently no studies have examined the effect of similar behavioral speech modifications on VP closure in children with 22qDS. The purpose of this pilot study was to explore the effect of loudness on VP closure during speech in children with 22qDS and persisting VPD. PATIENTS AND METHODS: Four children with 22qDS, posterior pharyngeal flap, and persisting mild VPD underwent pressure-flow testing while repeating words at habitual and increased loudness levels. Using a single-subject A-B design, descriptive statistics and graphical measures were used to examine differences in VP orifice area (VPA) and timing of closure in the habitual versus loud condition. RESULTS: Results were mixed. Median VPA decreased during some stimuli for 3 participants, but increased for 1 subject when speaking louder. Median duration of nasal airflow decreased for 3 participants in the loud condition. CONCLUSION: This study presents preliminary aerodynamic data regarding the plasticity of VP physiology in the 22qDS group. Further research is needed to determine how loudness impacts VP function in children with 22qDS.

[Catch-22? Wide variety of phenotypes associated with the chromosome 22q11 deletion syndrome in two patients]. / A 22-es csapdája? A 22q11 kromoszóma deletiós szindróma változatos klinikai megjelenése két eset kapcsán.

The chromosome 22q11 deletion syndrome may present with a variety of phenotypes. Its symptoms generally include a characteristic facial dysmorphisms and multiplex developmental disorders. Fluorescence in situ hybridization is the current method of choice for the diagnosis if typical multiple defects and/or symptoms are present. The authors present the history of two patients who were followed-up for minor anomalies and various developmental disorders for several years in the genetic counseling office of the authors, but definitive diagnosis was not established. However, when DNA samples of the two patients were recently tested with array comparative genome hybridization, a diagnostic method which has already been used in their institute for several years, the results indicated deletion of the 11.2 region on the long arm of chromosome 22 in both patients. The authors draw attention to the incidence and wide phenotypic spectrum of the chromosome 22q11 deletion syndrome, and show that its identification can be aided with the novel molecular cytogenetic method available in their laboratory.

Newborn screening programs: should 22q11 deletion syndrome be added?

The highly variable 22q11 deletion syndrome has been proposed for addition to newborn screening panels. A literature review investigated the incidence and prevalence, clinical features, and prognosis of 22q11 deletion syndrome and other issues related to newborn screening. Severe complications that could potentially be helped by screening include cardiac defects in 80% (with 20% having no outward signs to aid detection), hypocalcemia that can lead to seizures in 20% (though hypocalcemia is routinely investigated in sick newborns), and severe immune deficiency in <1% (which would be identified by some states' severe combined immunodeficiency screens). Other benefits that do not fit traditional goals of newborn screening include treatment for complications such as failure to thrive and developmental delay or preventing a "diagnostic odyssey." Although universal screening may prove the incidence to be >1:5000, undetected life-threatening effects occur in a minority of 22q11 deletion syndrome patients. Concerns include an untested screening technique, difficulty obtaining results in time for cardiac intervention, the chance of "vulnerable child syndrome" in mild cases, and possibly detecting congenital heart disease more efficiently by other means. Because addition of tests for highly variable conditions such as 22q11 deletion syndrome is likely to set a precedent for other syndromes, reevaluation of newborn screening criteria should be considered.

Prevalence and treatment of psychiatric disorders other than psychosis in children and adolescents with 22q11DS: Examining associations with social and role functioning.

Individuals with chromosome 22q11 deletion syndrome (22q11DS) have high rates of psychotic disorders. Less is known about their psychopathology and how it is treated prior to the peak period of risk for psychotic disorder. There is also a lack of evidence on how functioning is impacted by psychopathology in this population. The aim of this study was to investigate the prevalence and treatment of non-psychotic psychiatric disorders, and how these factors are associated with psychosocial functioning in children and adolescents with 22q11DS. 126 individuals with 22q11DS aged 8-17 participated in the study. Participants were assessed for psychiatric diagnoses, social and role functioning, anxiety and depressive symptoms and IQ. Information on current treatments was collected. 52.4% of the sample presented with at least one psychiatric disorder. Mood and anxiety disorders were the most frequent, followed by behavioural disorder. Individuals with a psychiatric disorder had significantly lower general, role and social functioning. Only 27% of participants with a psychiatric diagnosis were receiving any mental health treatment at the time of assessment. Findings suggest the high prevalence of psychiatric disorders in youth with 22q11DS, which significantly impacts psychosocial functioning. Despite this, psychiatric disorders tend to remain untreated in this population.

Severe laryngeal stenosis in newly born twins with 22q11.2 deletion syndrome: A case report.

Chromosome 22q11.2 deletion syndrome is common and presents with a range of clinical features from cardiac malformations to hypocalcemia. Laryngeal anomalies are not a common feature of this syndrome. We describe newly born twins who presented with unexpected severe birth depression secondary to severe type IV glottic webs requiring extensive resuscitation and emergency tracheostomy. They were diagnosed postnatally to have deletion of 22q11.2. The successful resuscitation of these infants at birth was only possible because they were born in a tertiary care hospital. This report shows the critical nature of prenatal diagnosis of 22q11.2 deletion syndrome.

Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention.

BACKGROUND: 22q11DS is a multiple anomaly syndrome involving intellectual and behavioral deficits, and increased risk for schizophrenia. As cognitive remediation (CR) has recently been found to improve cognition in younger patients with schizophrenia, we investigated the efficacy, feasibility, and fidelity of a remote, hybrid strategy, computerized CR program in youth with 22q11DS. METHODS: A longitudinal design was implemented in which 21 participants served as their own controls. Following an eight month baseline period in which no interventions were provided, cognitive coaches met with participants remotely for CR via video conferencing three times a week over a targeted 8month timeframe and facilitated their progress through the intervention, offering task-specific strategies. A subset of strategies were examined for fidelity. Outcomes were evaluated using a neurocognitive test battery at baseline, pre-treatment and post-treatment. RESULTS: All participants adhered to the intervention. The mean length of the treatment phase was 7.96months. A moderately high correlation (intraclass correlation coefficient, 0.73) was found for amount and type of strategies offered by coaches. Participants exhibited significant improvements (ES=.36-.55, p≤.009) in working memory, shifting attention and cognitive flexibility. All significant models were driven by improvements in pre to post-treatment scores. CONCLUSIONS: Based on our preliminary investigation, a remote, hybrid strategy, computerized CR program can be implemented with 22q11DS youth despite geographic location, health, and cognitive deficits. It appears effective in enhancing cognitive skills during the developmental period of adolescence, making this type of CR delivery useful for youth with 22q11DS transitioning into post-school environments.

Parent-led conferences as sites of medical work.

Conferences are novel sites for understanding medical work. Through describing styles of presentation that take place at conferences attended by patients and parents, this article highlights how clinicians on stage present ordinary and extraordinary aspects of medicine. Attention is drawn to the reaction of the parents in the audience. The power of the presenter to direct proceedings highlights the potential vulnerability of the audience. The relationship between clinician on stage and parents in the audience reflects the clinical relationship between doctor and patient. But through identifying insiders and outsiders, the conference setting also enables new relationships and collective identities to be formed. Drawing on an ethnographic study of rare disease conferences, this article extends understanding of medical work by identifying how conferences offer new ways of witnessing the clinical gaze, the doctor-patient relationship and the formation and enactment of a conference community.

Laryngeal abnormalities are frequent in the 22q11 deletion syndrome.

OBJECTIVES: The 22q11 microdeletion is a chromosomal disorder detected by fluorescence in situ hybridization (FISH). It has been known since the 80s, and is involved in many malformative syndromes (DiGeorge sequence, VCFS syndrome, etc.). Airway abnormalities are frequently localized in the larynx, as reported in the following series. METHODS: A retrospective chart review of laryngeal abnormalities and 22q11 deletion in a tertiary referral center. RESULTS: Five cases of laryngeal abnormalities associated to 22q11 deletion syndrome (DS) were found in a series of 35 cases. Abnormalities encountered were subglottic stenosis (3%), glottic web (9%), laryngeal paralysis (9%), vocal nodule (3%), laryngomalacia (3%) associated with bronchial malposition (3%). CONCLUSION: Laryngeal abnormalities are relatively common (14% in this series) and important to recognize with the 22q11 deletion syndrome, especially if cardiac surgery is planed. Conversely, in case of laryngeal abnormalities associated to other malformation (like facial dysmorphia or cardiac malformation), the 22q11 deletion must be searched.