Velo-Cardio-Facial Syndrome: 30 Years of Study

Velo-cardio-facial syndrome is one of the names that has been attached to one of the most common multiple anomaly syndromes in humans. The labels DiGeorge sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22, and Sedlačková syndrome have all been attached to the same disorder. Velo-cardio-facial syndrome has an expansive phenotype with more than 180 clinical features described that involve essentially every organ and system. The syndrome has drawn considerable attention because a number of common psychiatric illnesses are phenotypic features including attention deficit disorder, schizophrenia, and bipolar disorder. The expression is highly variable with some individuals being essentially normal at the mildest end of the spectrum, and the most severe cases having life-threatening and life-impairing problems. The syndrome is caused by a microdeletion from chromosome 22 at the q11.2 band. Although the large majority of affected individuals have identical 3 megabase deletions, less than 10% of cases have smaller deletions of 1.5 or 2.0 megabases. The 3 megabase deletion encompasses a region containing 40 genes. The syndrome has a population prevalence of approximately 1:2,000 in the United States, although incidence is higher. Although initially a clinical diagnosis, today velo-cardio-facial syndrome can be diagnosed with extremely high accuracy by fluorescence in situ hybridization and several other laboratory techniques. Clinical management is age dependent with acute medical problems such as congenital heart disease, immune disorders, feeding problems, cleft palate, and developmental disorders occupying management in infancy and preschool years. Management shifts to cognitive, behavioral, and learning disorders during school years, and then to the potential for psychiatric disorders including psychosis in late adolescence and adult years. Although the majority of people with velo-cardio-facial syndrome do not develop psychosis, the risk for severe psychiatric illness is 25 times higher for people affected with velo-cardio-facial syndrome than that of the general population. Therefore, interest in understanding the nature of psychiatric illness in the syndrome remains strong

Velopharyngeal Insufficiency: Diagnosis and Management

Journal articles relevant to the diagnosis and treatment of velopharyngeal insufficiency were reviewed. All studies ascertained by PubMed search were included. Recent findings: Studies reported on the application of magnetic resonance scanning, reliability tests of the International Working Group diagnostic protocol, the use of nasometry, and techniques designed to assess the function of the velopharyngeal mechanism. Treatment studies focused on outcomes in small samples of cases and complication rates from pharyngeal flap. One study discussed ineffective speech therapy procedures. Summary: There were relatively few studies this past year. Those that were published were hindered by small and heterogeneous sample sizes and occasionally by inappropriate methods for assessing outcomes. None of the findings will have a major impact on the current state-of-the-art for diagnosis of velopharyngeal insufficiency. The speech therapy study has a very important message that should be taken to heart by all clinicians involved in the management of children with clefts and craniofacial disorders

Abstention to Consumption: The Development of American Vegetarianism, 1817-1917

The history of vegetarianism in the United States has long been shrouded in myth, assumption and obfuscation. Vegetarianism as a vital ideological and political movement has often been presented--even by its proponents--as a product of twentieth century modernism, reflecting a rise in ethical consumer awareness. The historical record of the nineteenth century, however, tells a very different story. The notion that dietary choices could be connected with larger social and political goals was formulated during, and changed dramatically in the nineteenth century. This dissertation charts the rise and evolution of vegetarianism in the United States from 1817 until 1917. This project will present the first complete analysis of vegetarian activities in the United States during this time period. Through analysis of health and reform journals, personal papers, vegetarian society administrative papers, newspaper accounts and popular culture references, it is possible to chart distinct changes in the ways that vegetarians reacted to rapid socio-political change. Dividing the vegetarian movement in the United States into two distinct time periods gives insight into the changing nature of reform, gender roles, health care, consumerism and individualism. During this time period vegetarianism shifted from a method aimed at conquering social ills and injustice, to a path for personal strength and success in a newly individualistic, consumption-driven economy

Velo-Cardio-Facial Syndrome

Velocardiofacial syndrome (VCFS), also known as DiGeorge, conotruncal anomaly face, and Cayler syndromes, is caused by a microdeletion in the long arm of Chromosome 22. We review the history of the syndrome from the first clinical reports almost half a century ago to the current intriguing molecular findings associating genes from the microdeletion region and the physical and neuropsychiatric phenotype of the syndrome. Velocardiofacial syndrome has a wide spectrum of more than 200 physical manifestations including palate and cardiac anomalies. Yet, the most challenging manifestations of VCFS are the learning disabilities and neuropsychiatric disorders. As VCFS is relatively common and as up to one third of the participants with VCFS develop schizophrenia-like psychotic disorder, the syndrome is the most commonly known genetic risk factor to schizophrenia. Identifying the genetic, cognitive, and psychiatric risk factors for VCFS-schizophrenia is under the focus of intensive research

Velo-Cardio-Facial Syndrome

Purpose of review: Velo-cardio-facial syndrome has emerged from obscurity to become one of the most researched disorders this past decade. It is one of the most common genetic syndromes in humans, the most common contiguous gene syndrome in humans, the most common syndrome of cleft palate, and the most common syndrome of conotruncal heart malformations. Velo-cardio-facial syndrome has an expansive phenotype, a factor reflected in the wide range of studies that cover both clinical features and molecular genetics. In this review, we cover multiple areas of research during the past year, including psychiatric disorders, neuroimaging, and the delineation of clinical features. Recent findings: The identification of candidate genes for heart anomalies, mental illness, and other clinical phenotypes has been reported in the past year with a focus on TBX1 for cardiac and craniofacial phenotypes and COMT and PRODH for psychiatric disorders. The expansive phenotype of velo-cardio-facial syndrome continues to grow with new behavioral and structural anomalies reported. Treatment issues are beginning to draw attention, although most authors continue to focus on diagnostic issues. Summary: Its high population prevalence, estimated to be as common as 1:2000 has sparked a large amount of research, as has the model the syndrome serves for identifying the causes of mental illness and learning disabilities, but it is obvious that more information is needed. Intensive scrutiny of velo-cardio-facial syndrome will undoubtedly continue for many years to come with the hope that researchers will turn more of their attention to treatment and treatment outcomes

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

Objective: To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS). Method: 70 youth with VCFS, 27 siblings of youth with VCFS and 25 community controls were followed from childhood (Mean age = 11.8 years) into mid-adolescence (mean age 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time point. Results: Major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positive rates, the best predictor of adolescent prodromal psychotic symptoms was parent ratings of childhood odd/eccentric symptoms and child performance on a measure of executive functioning, the Wisconsin Card Sorting Test. Conclusions: Similar to the non-VCFS prodromal psychosis literature, a combination of cognitive and psychiatric variables appears to predict psychosis in adolescence. A child with VCFS who screens positive is noteworthy and demands clinical attention

22q11.2 Deletion Syndrome: Are Motor Deficits More Than Expected for IQ Level?

To examine motor function in children with 22q11.2 deletion syndrome (22q11.2) and a Full Scale IQ (FSIQ) comparable control group. This study was part of a prospective study of neuropsychological function in children 9 to 15 years of age with 22q11.2 and community control subjects and included children from these two populations with comparable FSIQs. Verbal IQs on the WISC-R for 40 children with 22q11.2 (88.4) and 24 community control subjects (87.2) were not different (P=.563). However, the performance IQs were (22q11.2; 81.1 vs community controls; 89.3;

Cervical Vascular and Upper Airway Asymmetry in Velo-Cardio-Facial Syndrome: Correlation of Nasopharyngoscopy With MRA

Purpose Velo-cardio-facial syndrome (VCFS), the most common genetic syndrome causing cleft palate, is associated with internal carotid and vertebral artery anomalies, as well as upper airway asymmetry. Medially displaced internal carotid arteries, often immediately submucosal, present a risk of vascular injury during pharyngeal flap surgery for velopharyngeal insufficiency (VPI). We evaluate the frequency and spectrum of cervical vascular anomalies in a large cohort of VCFS patients correlating MRA with nasopharyngolaryngoscopy in detecting at risk carotid arteries. Furthermore, we assess the relationship with respect to laterality between cervical vascular patterns and the asymmetric abnormalities of these subjects’ upper airways. Methods Cervical MRAs of 86 subjects with VCFS and 50 control subjects were independently reviewed by three neuroradiologists. The course of the internal carotid and vertebral arteries was identified within the pharyngeal soft tissues. Medial deviation, level of bifurcation, dominance, anomalous origin, and vessel tortuosity were recorded. Nasopharyngoscopy examinations were available for retrospective review in 43 patients and were assessed for palatal and posterior pharyngeal wall symmetry, true vocal cord motion and size, and for the presence or absence of carotid pulsations. The endoscopic findings were compared with MRA results. Results Of the 86 subjects, 80 (93%) had one or more vascular anomalies. 42 subjects (49%) were found to have medial deviation of at least one internal carotid artery. In 24 subjects (28%) the anomalous internal carotid artery was directly submucosal; four of these were bilateral (5% of the total sample, 17% of those with a submucosal internal carotid). Other carotid anomalies included low carotid bifurcation (44 subjects or 51%), anomalous origin of the right common carotid (32 cases, or 37%), and two cases of internal carotid agenesis/hypoplasia. Vertebral artery anomalies included vessel tortuosity (34 cases, or 40%), hypoplasia (10 cases, or 12%), looping (4 cases, or 5%), and one case of a double left vertebral artery. Though patients in our study showed an asymmetric distribution of vascular anomalies, no association was found between the laterality of palatal motion, pharyngeal fullness, or laryngeal movement and structure with ipsilateral vertebral or carotid artery anomalies. Of the 33 pulsatile carotid arteries visualized at nasopharyngoscopy, only nine were found to be submucosal on MRA. In contrast, 11 submucosal carotid arteries confirmed at MRA demonstrated no visible pulsations. Positive and negative predictive values of pulsative arteries seen endoscopically for MRA confirmation of a submucosal carotid course was 27% and 79% respectively. Conclusions Carotid and vertebral artery anomalies are common in VCFS including marked medial deviation of the internal carotid artery in close proximity to the donor site for pharyngeal flap surgery. Lack of correlation between laterality of vascular anomalies and upper airway structural asymmetry in VCFS does not support the hypothesis that palatal, pharyngeal, and laryngeal anomalies are due to secondary developmental sequences caused by in utero vascular insufficiency. The presence or absence of carotid pulsations seen by nasopharyngoscopy does not correlate with the carotid arterial depth identified on MRA. Furthermore, identification of the relative medial–lateral retropharyngeal position of a submucosal carotid affords the opportunity to modify the surgical approach. These findings further support the routine use of pre-operative neck MRA in VCFS patients in surgical planning

The Longitudinal Course of Attention Deficit/Hyperactivity Disorder in Velo-Cardio-Facial Syndrome

OBJECTIVE: To evaluate predictors of persistence of attention deficit/hyperactivity disorder (ADHD) in a large sample of children with velo-cardio-facial syndrome (VCFS) with and without ADHD followed prospectively into adolescence. STUDY DESIGN: Children with VCFS with (n = 37) and without (n = 35) ADHD who were on average 11 years old at the baseline assessment and 15 years old at the follow-up assessment were comprehensively assessed with structured diagnostic interviews and assessments of behavioral, cognitive, social, school, and family functioning. Control participants both with and without ADHD were also followed prospectively. RESULTS: In adolescence, 65% of children with VCFS continued to have findings consistent with ADHD. Childhood predictors of persistence were higher rates of familial ADHD, having childhood depression, having higher levels of hyperactivity, and a larger number of intrusion errors on a verbal list learning test at baseline. Approximately 15% of children with VCFS who did not have ADHD at Time 1 met diagnostic criteria for ADHD at Time 2. All of these children had subthreshold ADHD symptoms at Time 1. CONCLUSIONS: These findings prospectively confirm that persistence of ADHD into adolescence in VCFS is predicted by childhood variables that have been previously documented in the non-VCFS ADHD literature

The Neural Correlates of Non-Spatial Working Memory in Velocardiofacial Syndrome (22q11.2 Deletion Syndrome)

Velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a neurogenetic disorder that is associated with both learning disabilities and a consistent neuropsychological phenotype, including deficits in executive function, visuospatial perception, and working memory. Anatomic imaging studies have identified significant volumetric reductions in the parietal lobe of individuals with VCFS, but several studies have reported that the frontal lobe is relatively preserved. We used functional magnetic resonance imaging to investigate the neural correlates of non-spatial working memory in 17 youths with VCFS, 10 of their unaffected siblings, and 10 community controls (with the same proportion of learning disabilities as the VCFS youths). Task performance of siblings tended to be more accurate than children with VCFS, who did not differ from community controls. All three-study groups recruited parietal regions that were equivalent in location and magnitude. Whereas the sibling group also recruited the dorsolateral prefrontal cortex (DLPFC), Broca\u27s area, and anterior cingulate, DLPFC activation was absent in the whole brain analyses of children with VCFS and controls. Moreover, the magnitude of frontal activation in VCFS participants was restricted relative to both siblings and controls. These findings suggest that VCFS participants exhibit frontal hypoactivation that is not attributable to performance. In addition, VCFS children and controls (many with idiopathic learning disabilities) appear to rely on phonological rehearsal to hold information on line instead of the DLPFC. Despite previous anatomic MRI reports of preserved frontal lobe volumes in VCFS therefore, these fMRI findings suggest that the frontal component of the distributed network subserving executive function and working memory may be disrupted in youth with this disorder