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Sample records for 22q11 shprintzen-digeorge critical

  1. Noonan like appearance and familial deletion of the 22q11 Shprintzen-DiGeorge critical region

    SciTech Connect

    Piussan, C.; Mathieu, M.; Boudailliez, B.

    1994-09-01

    Shprintzen velocardiofacial syndrome (VCFS) and reported cases of autosomal dominant DiGeorge sequence (DGS) both belong to a heterogeneous developmental field defect due to the familial segregation of a 22q11 deletion. Two sisters present with mental retardation, dysmorphia and multiple congenital anomalies. The eldest has a Noonan-like appearance; short stature, short webbed neck, low posterior hairline, widely spaced nipples, hemivertebrae, speech disability and mild hypoparathyroidism. Her younger sister has prominent eyes, floppy ears, pulmonary valvular stenosis, hypoplastic right kidney, left multicystic kidney, hypoparathyroidism and renal failure causing death at age 3. Their retarded mother has a typical Shprintzen phenotype and no hypoparathyroidism. A deletion of the critical DiGeorge-Shprintzen conotruncal malformation region was found by FISH in the mother and her Noonan-like daughter. In the mother`s family exist 3 cleft palates, an imperforate anus, a stillbirth and one infant died at age 3 months because of heart malformation. To our knowledge, another case of Noonan-like appearance in a DG patient affected with monosomy 22q11 has been reported in 1992 by Wilson et al. Whether resulting from the hemizygosity of a gene or from the deletion of contiguous genes, the wide DGS-VCFS spectrum encompasses quite variable phenotypes, discordant for palatal and conotruncal defects as well as for hypoparathyroidism, dysmorphic features and multiple congenital anomalies. Physical mapping of both the large 22q11 region commonly lost and the smallest deletion sufficient to produce DGS has been done and may account for the broadening spectrum, the variable expression and the frequently delayed diagnosis of this syndrome.

  2. Localization of the human mitochondrial citrate transporter protein gene to chromosome 22q11 in the DiGeorge syndrome critical region

    SciTech Connect

    Heisterkamp, N.; Hoeve, J.T.; Groffen, J.

    1995-09-20

    A high percentage of patients with DiGeorge syndrome and velo-cardio-facial syndrome have interstitial deletions on chromosome 22q11. The shortest region of overlap is currently estimated to be around 500 kb. Two segments of DNA from chromosome 22q11, located 160 kb apart, were cloned because they contained NotI restriction enzyme sites. In the current study we demonstrate that these segments are absent from chromosomes 22 carrying microdeletions of two different DiGeorge patients. Fluorescence in situ and Southern blot hybridization was further used to show that this locus is within the DiGeorge critical region. Phylogenetically conserved sequences adjacent to one of the two NotI sites hybridized to mRNAs in different human cell lines. cDNAs isolated with a probe from this segment showed it to contain the gene for the human mitochondrial citrate transporter protein. Deletion of this gene in DiGeorge may contribute to the mental deficiency seen in the patients. 35 refs., 5 figs.

  3. 22q11 deletion syndrome: current perspective

    PubMed Central

    Hacıhamdioğlu, Bülent; Hacıhamdioğlu, Duygu; Delil, Kenan

    2015-01-01

    Chromosome 22q11 is characterized by the presence of chromosome-specific low-copy repeats or segmental duplications. This region of the chromosome is very unstable and susceptible to mutations. The misalignment of low-copy repeats during nonallelic homologous recombination leads to the deletion of the 22q11.2 region, which results in 22q11 deletion syndrome (22q11DS). The 22q11.2 deletion is associated with a wide variety of phenotypes. The term 22q11DS is an umbrella term that is used to encompass all 22q11.2 deletion-associated phenotypes. The haploinsufficiency of genes located at 22q11.2 affects the early morphogenesis of the pharyngeal arches, heart, skeleton, and brain. TBX1 is the most important gene for 22q11DS. This syndrome can ultimately affect many organs or systems; therefore, it has a very wide phenotypic spectrum. An increasing amount of information is available related to the pathogenesis, clinical phenotypes, and management of this syndrome in recent years. This review summarizes the current clinical and genetic status related to 22q11DS. PMID:26056486

  4. Microdeletion 22q11 and oesophageal atresia

    PubMed Central

    Digilio, M. C.; Marino, B.; Bagolan, P.; Giannotti, A.; Dallapiccola, B.

    1999-01-01

    Oesophageal atresia (OA) is a congenital defect associated with additional malformations in 30-70% of the cases. In particular, OA is a component of the VACTERL association. Since some major features of the VACTERL association, including conotruncal heart defect, radial aplasia, and anal atresia, have been found in patients with microdeletion 22q11.2 (del(22q11.2)), we have screened for del(22q11.2) by fluorescent in situ hybridisation (FISH) in 15 syndromic patients with OA. Del(22q11.2) was detected in one of them, presenting with OA, tetralogy of Fallot, anal atresia, neonatal hypocalcaemia, and subtle facial anomalies resembling those of velocardiofacial syndrome. The occurrence of del(22q11.2) in our series of patients with OA is low (1/15), but this chromosomal anomaly should be included among causative factors of malformation complexes with OA. In addition, clinical variability of del(22q11.2) syndrome is further corroborated with inclusion of OA in the list of the findings associated with the deletion.


Keywords: microdeletion 22q11; oesophageal atresia; VACTERL association; velocardiofacial syndrome PMID:10051013

  5. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome

    PubMed Central

    Meechan, Daniel W.; Tucker, Eric S.; Maynard, Thomas M.; LaMantia, Anthony-Samuel

    2009-01-01

    The 22q11 deletion (or DiGeorge) syndrome (22q11DS), the result of a 1.5- to 3-megabase hemizygous deletion on human chromosome 22, results in dramatically increased susceptibility for “diseases of cortical connectivity” thought to arise during development, including schizophrenia and autism. We show that diminished dosage of the genes deleted in the 1.5-megabase 22q11 minimal critical deleted region in a mouse model of 22q11DS specifically compromises neurogenesis and subsequent differentiation in the cerebral cortex. Proliferation of basal, but not apical, progenitors is disrupted, and subsequently, the frequency of layer 2/3, but not layer 5/6, projection neurons is altered. This change is paralleled by aberrant distribution of parvalbumin-labeled interneurons in upper and lower cortical layers. Deletion of Tbx1 or Prodh (22q11 genes independently associated with 22q11DS phenotypes) does not similarly disrupt basal progenitors. However, expression analysis implicates additional 22q11 genes that are selectively expressed in cortical precursors. Thus, diminished 22q11 gene dosage disrupts cortical neurogenesis and interneuron migration. Such developmental disruption may alter cortical circuitry and establish vulnerability for developmental disorders, including schizophrenia and autism. PMID:19805316

  6. Minimum prevalence of chromosome 22q11 deletions

    SciTech Connect

    Wilson, D.I.; Cross, I.E.; Burn, J.

    1994-09-01

    Submicroscopic deletions from within chromosome 22q11 are associated with DiGeorge (DGS), velocardiofacial (VCFS) and conotruncal anomaly syndromes and isolated congenital heart defects. In 1993 our pediatric cardiologists clinically referred all children in whom a chromosome 22q11 deletion was suspected for fluorescent in situ hybridization studies using probes from the DGS critical region. 10 affected individuals have been identified to date from the children born in 1993 in the Northern Region served exclusively by our center. A further case, the subsequent pregnancy in one of these families was affected and terminated on the basis of a major heart malformation. In the years 1988-92, for which we have complete ascertainment, there were 1009 heart defects among 191,700 births (mean 202 per annum). Thus we estimate that chromosome 22q11 deletions were the cause of at least 5% of congenital heart disease. As not all children with chromosome 22q11 deletions have a heart defect, this gives an estimated minimum prevalence of 1/4000 live births.

  7. 22q11.2 deletion syndrome

    PubMed Central

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2016-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  8. Genetics Home Reference: 22q11.2 deletion syndrome

    MedlinePlus

    ... Home Health Conditions 22q11.2 deletion syndrome 22q11.2 deletion syndrome Enable Javascript to view the expand/ ... Download PDF Open All Close All Description 22q11.2 deletion syndrome (which is also known by several ...

  9. Genetics Home Reference: 22q11.2 duplication

    MedlinePlus

    ... Genetics Home Health Conditions 22q11.2 duplication 22q11.2 duplication Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 22q11.2 duplication is a condition caused by an extra ...

  10. Radial aplasia and chromosome 22q11 deletion.

    PubMed Central

    Digilio, M C; Giannotti, A; Marino, B; Guadagni, A M; Orzalesi, M; Dallapiccola, B

    1997-01-01

    We report on a neonate with deletion 22q11 (del22q11) presenting with facial dysmorphism, ocular coloboma, congenital heart defect, urogenital malformations, and unilateral radial aplasia. This malformation complex includes features frequently occurring in velocardiofacial syndrome as well as findings described in the CHARGE and VACTERL associations. To our knowledge, the present case is the first report of radial aplasia in del22q11. This observation further supports and extends the clinical variability of del22q11. Images PMID:9391893

  11. Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

    PubMed Central

    Meechan, Daniel W.; Tucker, Eric S.; Maynard, Thomas M.; LaMantia, Anthony-Samuel

    2012-01-01

    Interneurons are thought to be a primary pathogenic target for several behavioral disorders that arise during development, including schizophrenia and autism. It is not known, however, whether genetic lesions associated with these diseases disrupt established molecular mechanisms of interneuron development. We found that diminished 22q11.2 gene dosage—the primary genetic lesion in 22q11.2 deletion syndrome (22q11.2 DS)—specifically compromises the distribution of early-generated parvalbumin-expressing interneurons in the Large Deletion (LgDel) 22q11.2DS mouse model. This change reflects cell-autonomous disruption of interneuron migration caused by altered expression of the cytokine C-X-C chemokine receptor type 4 (Cxcr4), an established regulator of this process. Cxcr4 is specifically reduced in LgDel migrating interneurons, and genetic analysis confirms that diminished Cxcr4 alters interneuron migration in LgDel mice. Thus, diminished 22q11.2 gene dosage disrupts cortical circuit development by modifying a critical molecular signaling pathway via Cxcr4 that regulates cortical interneuron migration and placement. PMID:23091025

  12. Age-dependent microRNA control of synaptic plasticity in 22q11 deletion syndrome and schizophrenia

    PubMed Central

    Earls, Laurie R.; Fricke, R. Gaines; Yu, Jing; Berry, Raymond B.; Baldwin, Lisa T.; Zakharenko, Stanislav S.

    2012-01-01

    The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5–3Mb region of chromosome 22. 22q11DS constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2), which is responsible for loading Ca2+ into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca2+ load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of Dgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in Dgcr8+/− mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia. PMID:23055483

  13. Mapping cortical thickness in children with 22q11.2 deletions.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Dutton, Rebecca A; Tran, Helen; Zimmermann, Lara; Sun, Daqiang; Geaga, Jennifer A; Simon, Tony J; Glahn, David C; Cannon, Tyrone D; Emanuel, Beverly S; Toga, Arthur W; Thompson, Paul M

    2007-08-01

    The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome, 22q11.2DS) involves cardiac and craniofacial anomalies, marked deficits in visuospatial cognition, and elevated rates of psychosis. Although the mechanism is unknown, characteristic brain alterations may predispose to development of psychosis and cognitive deficits in 22q11DS. We applied cortical pattern matching and new methods for measuring cortical thickness in millimeters to structural magnetic resonance images of 21 children with confirmed 22q11.2 deletions and 13 demographically matched healthy comparison subjects. Thickness was mapped at 65 536 homologous points, based on 3-dimensional distance from the cortical gray-white matter interface to the external gray-cerebrospinal fluid boundary. A pattern of regionally specific cortical thinning was observed in superior parietal cortices and right parietooccipital cortex, regions critical for visuospatial processing, and bilaterally in the most inferior portion of the inferior frontal gyrus (pars orbitalis), a key area for language development. Several of the 30 genes encoded in the deleted segment are highly expressed in the developing brain and known to affect early neuronal migration. These brain maps reveal how haploinsufficiency for such genes can affect cortical development and suggest a possible underlying pathophysiology of the neurobehavioral phenotype. PMID:17056649

  14. Genetic Counseling for the 22q11.2 Deletion

    ERIC Educational Resources Information Center

    McDonald-McGinn, Donna M.; Zackai, Elaine H.

    2008-01-01

    Because of advances in palliative medical care, children with the 22q11.2 deletion syndrome are surviving into adulthood. An increase in reproductive fitness will likely follow necessitating enhanced access to genetic counseling for these patients and their families. Primary care physicians/obstetric practitioners are in a unique position to…

  15. Developmental Trajectories in 22q11.2 Deletion

    PubMed Central

    Swillen, Ann; McDonald-McGinn, Donna M.

    2016-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000–4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70–84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions. PMID:25989227

  16. Developmental trajectories in 22q11.2 deletion.

    PubMed

    Swillen, Ann; McDonald-McGinn, Donna

    2015-06-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000-4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70-84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions.

  17. Divergent Patterns of Social Cognition Performance in Autism and 22q11.2 Deletion Syndrome (22q11DS)

    ERIC Educational Resources Information Center

    McCabe, Kathryn L.; Melville, Jessica L.; Rich, Dominique; Strutt, Paul A.; Cooper, Gavin; Loughland, Carmel M.; Schall, Ulrich; Campbell, Linda E.

    2013-01-01

    Individuals with developmental disorders frequently report a range of social cognition deficits including difficulties identifying facial displays of emotion. This study examined the specificity of face emotion processing deficits in adolescents with either autism or 22q11DS compared to typically developing (TD) controls. Two tasks (face emotion…

  18. Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome

    PubMed Central

    Chakraborty, D; Bernal, A J; Schoch, K; Howard, T D; Ip, E H; Hooper, S R; Keshavan, M S; Jirtle, R L; Shashi, V

    2012-01-01

    Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects. The purpose of this study was to determine if the expression levels of DGCR6 and its duplicate copy DGCR6L in 22q11DS subjects are associated with the parent-of-origin of the deletion and childhood psychopathologies. Our investigation showed no evidence of parent-of-origin-related differences in expression of both DGCR6 and DGCR6L. However, we found that the variability in DGCR6 expression was significantly greater in 22q11DS children than in age and gender-matched control individuals. Children with 22q11DS who had anxiety disorders had significantly lower DGCR6 expression, especially in subjects with the deletion on the maternal chromosome, despite the lack of imprinting. Our findings indicate that epigenetic mechanisms other than imprinting contribute to the dysregulation of these genes and the associated childhood psychopathologies observed in individuals with 22q11DS. Further studies are now needed to test the usefulness of DGCR6 and DGCR6L expression and alterations in the epigenome at these loci in predicting childhood anxiety and associated adult-onset pathologies in 22q11DS subjects. PMID:22832905

  19. Candidate Genes and the Behavioral Phenotype in 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Prasad, Sarah E.; Howley, Sarah; Murphy, Kieran C.

    2008-01-01

    There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk…

  20. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    ERIC Educational Resources Information Center

    Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

  1. Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development

    PubMed Central

    Meechan, Daniel W.; Maynard, Thomas M.; Fernandez, Alejandra; Karpinski, Beverly A.; Rothblat, Lawrence A.; LaMantia, Anthony S.

    2015-01-01

    Understanding the developmental etiology of autistic spectrum disorders, attention deficit/hyperactivity disorder and schizophrenia remains a major challenge for establishing new diagnostic and therapeutic approaches to these common, difficult-to-treat diseases that compromise neural circuits in the cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD, ADHD, and SCZ deficits; another is the complexity of mutations associated with each, and a third is the difficulty of analyzing disrupted development in at-risk or affected human fetuses. The identification of distinct genetic syndromes that include behavioral deficits similar to those in ASD, ADHC and SCZ provides a critical starting point for meeting this challenge. We summarize clinical and behavioral impairments in children and adults with one such genetic syndrome, the 22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features, including cardiovascular and craniofacial anomalies, 22q11DS patients have a high incidence of brain structural, functional, and behavioral deficits that reflect cerebral cortical dysfunction and fall within the spectrum that defines ASD, ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent genetic “model” syndrome in patients can be defined and analyzed mechanistically using genomically accurate mouse models of the deletion that causes 22q11DS. We conclude that “modeling a model”, in this case 22q11DS as a model for idiopathic ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently seen in 22q11DS patients, in genetically engineered mice provides a foundation for understanding the causes and improving diagnosis and therapy for these disorders of cortical circuit development. PMID:25866365

  2. Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11) deletion syndrome

    PubMed Central

    Karpinski, Beverly A.; Maynard, Thomas M.; Fralish, Matthew S.; Nuwayhid, Samer; Zohn, Irene E.; Moody, Sally A.; LaMantia, Anthony-S.

    2014-01-01

    ABSTRACT We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia – debilitating feeding, swallowing and nutrition difficulties from birth onward – within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal (IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS. PMID:24357327

  3. Disrupted anatomic networks in the 22q11.2 deletion syndrome.

    PubMed

    Schmitt, J Eric; Yi, James; Calkins, Monica E; Ruparel, Kosha; Roalf, David R; Cassidy, Amy; Souders, Margaret C; Satterthwaite, Theodore D; McDonald-McGinn, Donna M; Zackai, Elaine H; Gur, Ruben C; Emanuel, Beverly S; Gur, Raquel E

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS) is an uncommon genetic disorder with an increased risk of psychosis. Although the neural substrates of psychosis and schizophrenia are not well understood, aberrations in cortical networks represent intriguing potential mechanisms. Investigations of anatomic networks within 22q11DS are sparse. We investigated group differences in anatomic network structure in 48 individuals with 22q11DS and 370 typically developing controls by analyzing covariance patterns in cortical thickness among 68 regions of interest using graph theoretical models. Subjects with 22q11DS had less robust geographic organization relative to the control group, particularly in the occipital and parietal lobes. Multiple global graph theoretical statistics were decreased in 22q11DS. These results are consistent with prior studies demonstrating decreased connectivity in 22q11DS using other neuroimaging methodologies. PMID:27622139

  4. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    PubMed Central

    Wong, Ling M; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. We examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with 22q11.2DS (n = 47) and typically developing controls (n = 49) ages 6–15 years saw images within a grid and after a delay, then indicated the positions of the images in the correct temporal order. Children with 22q11.2DS made more spatial and temporal errors than controls. Females with 22q11.2DS made more spatial and temporal errors than males. These results extend findings of impaired spatiotemporal processing into the memory domain in 22q11.2DS by documenting their influence on working memory performance. PMID:24679349

  5. Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.

    PubMed Central

    Carlson, C; Sirotkin, H; Pandita, R; Goldberg, R; McKie, J; Wadey, R; Patanjali, S R; Weissman, S M; Anyane-Yeboa, K; Warburton, D; Scambler, P; Shprintzen, R; Kucherlapati, R; Morrow, B E

    1997-01-01

    Velo-cardio-facial syndrome (VCFS) is a relatively common developmental disorder characterized by craniofacial anomalies and conotruncal heart defects. Many VCFS patients have hemizygous deletions for a part of 22q11, suggesting that haploinsufficiency in this region is responsible for its etiology. Because most cases of VCFS are sporadic, portions of 22q11 may be prone to rearrangement. To understand the molecular basis for chromosomal deletions, we defined the extent of the deletion, by genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11. We found that 83% had a deletion and >90% of these had a similar approximately 3 Mb deletion, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. We found no correlation between the presence or size of the deletion and the phenotype. To further define the chromosomal breakpoints among the VCFS patients, we developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that includes deletion breakpoints was constructed, incorporating genes and expressed sequence tags (ESTs) isolated by the hybridization selection method. The ordered markers were used to examine the two separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, we were able to map the chromosome breakpoints within a single cosmid. A 480-kb critical region for VCFS has been delineated, including the genes for GSCL, CTP, CLTD, HIRA, and TMVCF, as well as a number of novel ordered ESTs. PMID:9326327

  6. Upper limb malformations in chromosome 22q11 deletions

    SciTech Connect

    Shalev, S.A.; Dar, H.; Barel, H.; Borochowitz, Z.

    1996-03-29

    We read with interest the report of Cormier-Daire et al. in a recent issue of the journal, describing upper limb malformations in DiGeorge syndrome. We observed a family with this group of rare clinical expression of chromosome 22q11 deletions. The proposita was examined in our clinic when she was 4 years old. She was mildly mentally retarded. Clinical evaluation showed normal growth, long thin nose with squared tip, nasal speech, and abundant scalp hair and no cardiac anomalies. The girl was accompanied by her mother. Facial similarities were noted between the two. The mother reported to be treated with oral calcium due to hypoparathyroidism, diagnosed several years ago. Clinical evaluation showed wide flat face, short stature, mild mental retardation, slight hypertelorism, peculiar nose similar to her daughter`s, and nasal speech. No cardiac anomalies were found. Recently, a brother was born. Clinical examination documented large ventriculo-septal defect, retrognathia, narrow palpebral fissures, and long thin nose with squared tip. 1 ref.

  7. 22q11 Deletion Syndrome: A Genetic Subtype of Schizophrenia

    PubMed Central

    Bassett, Anne S.; Chow, Eva W.C.

    2012-01-01

    Schizophrenia is likely to be caused by several susceptibility genes and may have environmental factors that interact with susceptibility genes and/or nongenetic causes. Recent evidence supports the likelihood that 22q11 Deletion Syndrome (22qDS) represents an identifiable genetic subtype of schizophrenia. 22qDS is an under-recognized genetic syndrome associated with microdeletions on chromosome 22 and a variable expression that often includes mild congenital dysmorphic features, hypernasal speech, and learning difficulties. Initial evidence indicates that a minority of patients with schizophrenia (~2%) may have 22qDS and that prevalence may be somewhat higher in subpopulations with developmental delay. This paper proposes clinical criteria (including facial features, learning disabilities, hypernasal speech, congenital heart defects and other congenital anomalies) to aid in identifying patients with schizophrenia who may have this subtype and outlines features that may increase the index of suspicion for this syndrome. Although no specific causal gene or genes have yet been identified in the deletion region, 22qDS may represent a more homogeneous subtype of schizophrenia. This subtype may serve as a model for neurodevelopmental origins of schizophrenia that could aid in delineating etiologic and pathogenetic mechanisms. PMID:10509171

  8. White matter abnormalities in adults with 22q11 deletion syndrome with and without schizophrenia.

    PubMed

    da Silva Alves, Fabiana; Schmitz, Nicole; Bloemen, Oswald; van der Meer, Johan; Meijer, Julia; Boot, Erik; Nederveen, Aart; de Haan, Lieuwe; Linszen, Don; van Amelsvoort, Therese

    2011-10-01

    Dysfunction of cerebral white matter (WM) is a potential factor underlying the neurobiology of schizophrenia. People with 22q11 deletion syndrome have altered brain morphology and increased risk for schizophrenia, therefore decreased WM integrity may be related to schizophrenia in 22q11DS. We measured fractional anisotropy (FA) and WM volume in 27 adults with 22q11DS with schizophrenia (n=12, 22q11DS SCZ+) and without schizophrenia (n=15, 22q11DS SCZ-), 12 individuals with idiopathic schizophrenia and 31 age-matched healthy controls. We found widespread decreased WM volume in posterior and temporal brain areas and decreased FA in areas of the frontal cortex in the whole 22q11DS group compared to healthy controls. In 22q11DS SCZ+ compromised WM integrity included inferior frontal areas of parietal and occipital lobe. Idiopathic schizophrenia patients showed decreased FA in inferior frontal and insular regions compared to healthy controls. We found no WM alterations in 22q11DS SCZ+ vs. 22q11DS SCZ-. However, there was a negative correlation between FA and PANSS scores (Positive and Negative Symptom Scale) in the whole 22q11DS group in the inferior frontal, cingulate, insular and temporal areas. This is the first study to investigate WM integrity in adults with 22q11DS. Our results suggest that pervasive WM dysfunction is intrinsic to 22q11DS and that psychotic development in adults with 22q11DS involves similar brain areas as seen in schizophrenia in the general population.

  9. Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome.

    PubMed

    Weinberger, Ronnie; Yi, James; Calkins, Monica; Guri, Yael; McDonald-McGinn, Donna M; Emanuel, Beverly S; Zackai, Elaine H; Ruparel, Kosha; Carmel, Miri; Michaelovsky, Elena; Weizman, Abraham; Gur, Ruben C; Gur, Raquel E; Gothelf, Doron

    2016-10-01

    The 22q11.2 deletion syndrome (22q11DS) is associated with increased rates of psychotic disorders and cognitive deficits, but large scale studies are needed to elucidate their interaction. The objective of this two-center study was to identify the neurocognitive phenotype of individuals with 22q11DS and psychotic disorders. We hypothesized that psychotic 22q11DS individuals compared to nonpsychotic deleted individuals would have more severe neurocognitive deficits, especially in executive function and social cognition. These deficits would be present when compared to IQ- matched individuals with Williams Syndrome (WS). Three groups were ascertained from the Tel Aviv and Philadelphia centers: 22q11DS individuals with a psychotic disorder (n=31), nonpsychotic 22q11DS (n=86) and typically-developing controls (TD, n=828). In Tel Aviv a group of individuals with WS (n=18) matched in IQ to the 22q11DS psychotic group was also included. The Penn Computerized Neurocognitive Battery (CNB) was used to assess a wide-range of cognitive functions and all patients underwent structured psychiatric evaluations. 22q11DS individuals performed poorly on all CNB domains compared to TD. Participants with 22q11DS and psychosis, compared to nonpsychotic 22q11DS, had more severe deficits in global neurocognitive performance (GNP), executive function, social cognition and episodic memory domains. The primary deficits were also significant when comparing the Tel Aviv 22q11DS psychotic group to IQ-matched individuals with WS. In conclusion, 22q11DS individuals with a psychotic disorder have specific neurocognitive deficits that are reliably identified cross nationality using the CNB. These cognitive dysfunctions should be further studied as potential endophenotypes of psychosis in 22q11DS and as targets for intervention. PMID:27524298

  10. Velo-Cardio-Facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region

    SciTech Connect

    Nickel, R.E.; Pillers, D.M.; Merkens, M.; Magenis, R.E.; Zonana, J.; Driscoll, D.A.; Emanuel, B.S.

    1994-10-01

    Approximately 5% of children with neural tube defects (NTDs) have a congenital heart defect and/or cleft lip and palate. The cause of isolated meningomyelocele, congenital heart defects, or cleft lip and palate has been largely thought to be multifactorial. However, chromosomal, teratogenic, and single gene causes of combinations of NTDs with congenital heart defects and/or cleft lip and palate have been reported. We report on 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of velo-cardio-facial syndrome (VCFS); both have bifid uvula. The third child had DiGeorge sequence (DGS). The association of NTDs with 22q11 deletion has not been reported previously. An accurate diagnosis of the 22q11 deletion is critical as this micro-deletion and its associated clinical problems is transmitted as an autosomal dominant trait due to the inheritance of the deletion-bearing chromosome. We recommend that all children with NTDs and congenital heart defects, with or without cleft palate, have cytogenetic and molecular studies performed to detect 22q11 deletions. 31 refs., 3 figs.

  11. Neurocognitive profile in 22q11 deletion syndrome and schizophrenia

    PubMed Central

    Chow, Eva W. C.; Watson, Mark; Young, Donald A.; Bassett, Anne S.

    2011-01-01

    Objective Schizophrenia is associated with neurocognitive deficits, but its etiologic heterogeneity may complicate the delineation of a neurocognitive profile. Schizophrenia associated with 22q11 Deletion Syndrome (22qDS) represents a more genetically homogeneous subtype for study. We hypothesized that in adults with 22qDS the neurocognitive profiles would differ between those with and without schizophrenia. Method Using a comprehensive battery of tests, we compared the neurocognitive performance profiles in those with schizophrenia (n=27; 14 M, 13 F; mean age=30.6 years, SD=7.7 years) and those with no history of psychosis (n=29; 16 M, 13 F; mean age=25.0 years, SD=9.0 years). Results The 22qDS groups with and without schizophrenia had similar mean estimated IQ (71.6, SD=8.2 and 74.8, SD=6.1, respectively) and academic achievement, however the neurocognitive profiles of the two groups differed significantly on multivariate analysis (F(24,31)=2.25, p=0.017). The group with schizophrenia performed significantly more poorly on tests of motor skills, verbal learning, and social cognition (effect sizes≥0.8) after correction for multiple comparisons. Other tests, but not the attentional measures used, showed nominally significant differences. Conclusions In adults with 22qDS, the pattern of neurocognitive differences between those with and without schizophrenia appears similar to that between patients with schizophrenia and controls. Attentional dysfunction may be a more general feature of 22qDS. The findings support 22qDS-schizophrenia as a genetic model for neurodevelopmental investigations of schizophrenia. PMID:16753283

  12. Behavior in preschool children with the 22q11.2 deletion syndrome.

    PubMed

    Klaassen, Petra; Duijff, Sasja; Swanenburg de Veye, Henriette; Vorstman, Jacob; Beemer, Frits; Sinnema, Gerben

    2013-01-01

    Children with the 22q11.2 deletion syndrome (22q11DS) are at an increased risk of psychiatric problems from pre-adolescence; little is known, however, about behavioral problems at a preschool age and the relationship between speech and behavior in this group. Parents of 90 children (aged 1.42-5.99 years) with 22q11DS filled out the Child Behavior Checklist, documenting behaviors including speech problems. Their profiles were compared with those of a comparison group consisting of 33 children with nonsyndromic orofacial clefts without 22q11DS, since both children with 22q11DS and children with clefts are expected to have speech problems. In the 22q11DS group, data on intelligence was acquired by means of formal tests. Parents of children with 22q11DS reported significantly higher mean scores on withdrawn behavior, affective problems and pervasive developmental problems compared to children with nonsyndromic clefts. Approximately 30% of children with 22q11DS had a score above the 97th percentile on at least one of the behavior subscales, indicating psychopathology. In children with 22q11DS, the reported behavioral problems were not associated with speech problems. Behavioral problems were found in 30% of young children with 22q11DS and were unlikely to be caused by speech problems. Within the 22q11DS group, behavioral problems were not related to the degree of cognitive impairment. This shows that many children with 22q11DS, known to be at an increased risk of psychiatric problems from pre-adolescence, already show behavioral problems before the age of 6 years.

  13. Nasal dimple as part of the 22q11.2 deletion syndrome

    SciTech Connect

    Gripp, K.W.; Reed, L.A.; Emanuel, B.S. |

    1997-03-31

    The phenotype of the 22q11.2 microdeletion syndrome is quite variable. We describe 2 patients with a 22q11.2 deletion and a dimpled nasal tip, which, we suggest can be the extreme of the broad or bulbous nose commonly found in the 22q11.2 deletion syndrome, and should not be confused with the more severe nasal abnormalities seen in frontonasal dysplasia. 11 refs., 2 figs.

  14. Caregiver and adult patient perspectives on the importance of a diagnosis of 22q11.2 deletion syndrome

    PubMed Central

    Costain, G.; Chow, E. W. C.; Ray, P. N.; Bassett, A. S.

    2015-01-01

    Background Recent advances in genetics are particularly relevant in the field of intellectual disability (ID), where sub-microscopic deletions or duplications of genetic material are increasingly implicated as known or suspected causal factors. Data-driven reports on the impact of providing an aetiological explanation in ID are needed to help justify widespread use of new and expensive genetic technologies. Methods We conducted a survey of caregivers on the value of a genetic/aetiologic diagnosis of 22q11.2 deletion syndrome (22q11.2DS), the most common microdeletion syndrome in ID. We also surveyed the opinion of a high-functioning subset of adults with 22q11.2DS themselves. We used standard quantitative and qualitative methods to analyse the responses. Results In total, 73 of 118 surveys were returned (61.9%). There was convergence of quantitative and qualitative results, and consistency between adult patient and caregiver responses. A definitive molecular diagnosis of 22q11.2DS was a critical event with diverse positive repercussions, even if occurring later in life. Frequently cited benefits included greater understanding and certainty, newfound sense of purpose and a platform for advocacy, and increased opportunities to optimise medical, social and educational needs. Conclusions This is the first study to characterise the impact of a diagnosis of this representative microdeletion syndrome on adult patients and their families. The results both validate and expand on the theoretical benefits proposed by clinicians and researchers. The use of genome-wide microarray technologies will provide an increasing number of molecular diagnoses. The importance of a diagnosis of 22q11.2DS demonstrated here therefore has implications for changing attitudes about molecular genetic diagnosis that could benefit individuals with ID of currently unknown cause and their families. PMID:22142442

  15. 22q11.2 Deletions in Patients with Conotruncal Defects: Data from 1610 Consecutive Cases

    PubMed Central

    Peyvandi, Shabnam; Lupo, Philip J; Garbarini, Jennifer; Woyciechowski, Stacy; Edman, Sharon; Emanuel, Beverly S; Mitchell, Laura; Goldmuntz, Elizabeth

    2013-01-01

    Background The 22q11.2 deletion syndrome is characterized by multiple congenital anomalies including conotruncal cardiac defects. Identifying the patient with a 22q11.2 deletion (22q11del) can be challenging because many extracardiac features become apparent later in life. We sought to better define the cardiac phenotype associated with a 22q11del to help direct genetic testing. Methods 1,610 patients with conotruncal defects were sequentially tested for a 22q11del. Counts and frequencies for primary lesions and cardiac features were tabulated for those with and without a 22q11del. Logistic regression models investigated cardiac features that predicted deletion status in tetralogy of Fallot (TOF). Results Deletion frequency varied by primary anatomic phenotype. Regardless of the cardiac diagnosis, a concurrent aortic arch anomaly (AAA) was strongly associated with deletion status (OR 5.07, 95% CI: 3.66–7.04). In the TOF subset, the strongest predictor of deletion status was an AAA (OR 3.14, 95% CI: 1.87–5.27, p <0.001), followed by pulmonary valve atresia (OR 2.03, 95% CI: 1.02–4.02, p= 0.04). Among those with double outlet right ventricle and transposition of the great arteries, only those with an AAA had a 22q11del. However, five percent of patients with an isolated conoventricular ventricular septal defect and normal aortic arch anatomy had a 22q11del, while no one with an IAA-A had a 22q11del. Conclusion A subset of patients with conotruncal defects are at risk for a 22q11del. A concurrent AAA increases the risk regardless of the intracardiac anatomy. These findings help direct genetic screening for the 22q11.2 deletion syndrome in the cardiac patient. PMID:23604262

  16. Subtypes in 22q11.2 Deletion Syndrome Associated with Behaviour and Neurofacial Morphology

    ERIC Educational Resources Information Center

    Sinderberry, Brooke; Brown, Scott; Hammond, Peter; Stevens, Angela F.; Schall, Ulrich; Murphy, Declan G. M.; Murphy, Kieran C.; Campbell, Linda E.

    2013-01-01

    22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among…

  17. Cardiac Defects and Results of Cardiac Surgery in 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Carotti, Adriano; Digilio, Maria Cristina; Piacentini, Gerardo; Saffirio, Claudia; Di Donato, Roberto M.; Marino, Bruno

    2008-01-01

    Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic…

  18. Mathematical Learning Disabilities in Children with 22q11.2 Deletion Syndrome: A Review

    ERIC Educational Resources Information Center

    De Smedt, Bert; Swillen, Ann; Verschaffel, Lieven; Ghesquiere, Pol

    2009-01-01

    Mathematical learning disabilities (MLD) occur frequently in children with specific genetic disorders, like Turner syndrome, fragile X syndrome and neurofibromatosis. This review focuses on MLD in children with chromosome 22q11.2 deletion syndrome (22q11DS). This syndrome is the most common known microdeletion syndrome with a prevalence of at…

  19. Neural Substrates of Inhibitory Control Deficits in 22q11.2 Deletion Syndrome†

    PubMed Central

    Montojo, C.A.; Jalbrzikowski, M.; Congdon, E.; Domicoli, S.; Chow, C.; Dawson, C.; Karlsgodt, K.H.; Bilder, R.M.; Bearden, C.E.

    2015-01-01

    22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. PMID:24177988

  20. miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome

    PubMed Central

    Brzustowicz, Linda M.; Bassett, Anne S.

    2012-01-01

    In humans, the most common genomic disorder is a hemizygous deletion of a 1.5–3 Mb region of chromosome 22q11.2. The resultant 22q11.2 deletion syndrome (22q11.2DS) can affect multiple organ systems, and most notably includes cardiac, craniofacial, and neurodevelopmental defects. Individuals with 22q11.2DS have a 20–25-fold risk of developing schizophrenia compared to individuals from the general population, making 22q11.2DS the strongest known molecular genetic risk factor for schizophrenia. Although the deleted region includes DGCR8, a gene coding for a miRNA processing protein, the exact mechanism by which this deletion increases risk is unknown. Importantly, several lines of evidence suggest that miRNAs may modulate risk for schizophrenia in other, non-22q11.2DS populations. Here we present a theory which mechanistically explains the link between 22q11.2DS, miRNAs, and schizophrenia risk. We outline the testable predictions generated by this theory and present preliminary data in support of our model. Further experimental validation of this model could provide important insights into the etiology of both 22q11.2DS and more common forms of schizophrenia. PMID:23248646

  1. Structural Brain Abnormalities in Patients with Schizophrenia and 22q11 Deletion Syndrome

    PubMed Central

    Chow, Eva W.C.; Zipursky, Robert B.; Mikulis, David J.; Bassett, Anne S.

    2012-01-01

    Background 22q11 Deletion Syndrome is a genetic syndrome associated with an increased risk for developing schizophrenia. Brain abnormalities have been reported in 22q11 Deletion Syndrome, but little is known about whether differences in brain structure underlie the psychotic disorders associated with this syndrome. In the current study, we used magnetic resonance imaging to characterize the structural brain abnormalities found in adults who have both 22q11 Deletion Syndrome and schizophrenia. Methods Magnetic resonance imaging brain scans of 14 adults (7 male, 7 female) with 22q11 Deletion Syndrome and schizophrenia and 14 age- and gender-matched healthy volunteers were analyzed to derive measures of gray matter, white matter, and cerebrospinal fluid. Differences between the two groups were tested using student t tests. Results 22q11 Deletion Syndrome and schizophrenia subjects had significantly smaller total gray matter volume (t = 2.88, p < .01) and larger lateral ventricles (t = 4.08, p < .001) than healthy controls. Gray matter deficits were most prominent in the frontal and temporal lobes. Total white matter volumes did not differ between the two groups. Conclusions Findings from this 22q11 Deletion Syndrome and schizophrenia study are similar to those reported in other patients with schizophrenia, but only partially consistent with those reported in nonpsychotic children with 22q11 Deletion Syndrome. 22q11 Deletion Syndrome may provide a valuable genetic neurodevelop-mental model for investigating the relationship between abnormalities in brain development and the expression of schizophrenia. PMID:11839363

  2. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

    PubMed Central

    Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

    2015-01-01

    IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological

  3. Movement Disorders and Other Motor Abnormalities in Adults With 22q11.2 Deletion Syndrome

    PubMed Central

    Boot, Erik; Butcher, Nancy J; van Amelsvoort, Thérèse AMJ; Lang, Anthony E; Marras, Connie; Pondal, Margarita; Andrade, Danielle M; Fung, Wai Lun Alan; Bassett, Anne S

    2015-01-01

    Movement abnormalities are frequently reported in children with 22q11.2 deletion syndrome (22q11.2DS), but knowledge in this area is scarce in the increasing adult population. We report on five individuals illustrative of movement disorders and other motor abnormalities in adults with 22q11.2DS. In addition to an increased susceptibility to neuropsychiatric disorders, seizures, and early-onset Parkinson disease, the underlying brain dysfunction associated with 22q11.2DS may give rise to an increased vulnerability to multiple movement abnormalities, including those influenced by medications. Movement abnormalities may also be secondary to treatable endocrine diseases and congenital musculoskeletal abnormalities. We propose that movement abnormalities may be common in adults with 22q11.2DS and discuss the implications and challenges important to clinical practice. PMID:25684639

  4. Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms.

    PubMed

    Casarelli, Livia; Minnei, Maurizio; Pitzianti, Mariabernarda; Armando, Marco; Pontillo, Maria; Vicari, Stefano; Pasini, Augusto

    2016-10-01

    22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS. PMID:27548835

  5. Cognitive phenotype and psychiatric disorder in 22q11.2 deletion syndrome: A review.

    PubMed

    Biswas, Asit B; Furniss, Frederick

    2016-01-01

    The behavioural phenotype of 22q11.2 deletion syndrome syndrome (22q11DS), one of the most common human multiple anomaly syndromes, frequently includes intellectual disability (ID) together with high risk of diagnosis of psychotic disorders including schizophrenia. Candidate cognitive endophenotypes include problems with retrieval of contextual information from memory and in executive control and focussing of attention. 22q11DS may offer a model of the relationship between ID and risk of psychiatric disorder. This paper reviews research on the relationship between the cognitive phenotype and the development of psychiatric disorders in 22q11DS. Aspects of cognitive function including verbal I.Q., visual memory, and executive function, are associated with mental health outcome in people with 22q11DS. This relationship may result from a common neurobiological basis for the cognitive difficulties and psychiatric disorders. Some of the cognitive difficulties experienced by people with 22q11DS, especially in attention, memory retrieval, and face processing, may, however, in themselves constitute risk factors for development of hallucinations and paranoid delusions. Future research into factors leading to psychiatric disorder in people with 22q11DS should include assessment of social and psychological factors including life events, symptoms associated with trauma, attachment, and self-esteem, which together with cognitive risk factors may mediate mental health outcome. PMID:26942704

  6. Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype?

    PubMed Central

    Angkustsiri, Kathleen; Goodlin-Jones, Beth; Deprey, Lesley; Brahmbhatt, Khyati; Harris, Susan; Simon, Tony J.

    2015-01-01

    High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation measure (Autism Diagnostic Observation Schedule) and suggests that ASD is not as common as previously reported in 22q11.2DS. Differences in methodology, along with comorbid conditions such as anxiety, likely contribute to false elevations in ASD prevalence and information from multiple sources should be included in the evaluation of ASD. PMID:24045981

  7. Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Dutton, Rebecca A; Lee, Agatha D; Simon, Tony J; Cannon, Tyrone D; Emanuel, Beverly S; McDonald-McGinn, Donna; Zackai, Elaine H; Thompson, Paul M

    2009-01-01

    The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is a neurogenetic condition associated with visuospatial deficits, as well as elevated rates of attentional disturbance, mood disorder, and psychosis. Previously, we detected pronounced cortical thinning in superior parietal and right parieto-occipital cortices in patients with this syndrome, regions critical for visuospatial processing. Here we applied cortical pattern-matching algorithms to structural magnetic resonance images obtained from 21 children with confirmed 22q11.2 deletions (ages 8-17) and 13 demographically matched comparison subjects, in order to map cortical thickness across the medial hemispheric surfaces. In addition, cortical models were remeshed in frequency space to compute their surface complexity. Cortical maps revealed a pattern of localized thinning in the ventromedial occipital-temporal cortex, critical for visuospatial representation, and the anterior cingulate, a key area for attentional control. However, children with 22q11.2DS showed significantly increased gyral complexity bilaterally in occipital cortex. Regional gray matter volumes, particularly in medial frontal cortex, were strongly correlated with both verbal and nonverbal cognitive functions. These findings suggest that aberrant parieto-occipital brain development, as evidenced by both increased complexity and cortical thinning in these regions, may be a neural substrate for the deficits in visuospatial and numerical understanding characteristic of this syndrome. PMID:18483006

  8. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    PubMed Central

    Deng, Kathy; Nanda, Deepak

    2016-01-01

    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  9. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome.

    PubMed

    Pachtman, Sarah L; Deng, Kathy; Nanda, Deepak

    2016-01-01

    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  10. Social Impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a Different Endophenotype?

    ERIC Educational Resources Information Center

    Angkustsiri, Kathleen; Goodlin-Jones, Beth; Deprey, Lesley; Brahmbhatt, Khyati; Harris, Susan; Simon, Tony J.

    2014-01-01

    High prevalence of autism spectrum disorders (ASD) has been reported in 22q11.2DS, although this has been based solely on parent report measures. This study describes the presence of ASD using a procedure more similar to that used in clinical practice by incorporating history (Social Communication Questionnaire) AND a standardized observation…

  11. Mouse Models of 22q11.2-Associated Autism Spectrum Disorder

    PubMed Central

    Hiroi, Noboru; Hiramoto, Takeshi; Harper, Kathryn M.; Suzuki, Go; Boku, Shuken

    2013-01-01

    Copy number variation (CNV) of human chromosome 22q11.2 is associated with an elevated rate of autism spectrum disorder (ASD) and represents one of syndromic ASDs with rare genetic variants. However, the precise genetic basis of this association remains unclear due to its relatively large hemizygous and duplication region, including more than 30 genes. Previous studies using genetic mouse models suggested that although not all 22q11.2 genes contribute to ASD symptomatology, more than one 22q11.2 genes have distinct phenotypic targets for ASD symptoms. Our data show that deficiency of the two 22q11.2 genesTbx1 and Sept5 causes distinct phenotypic sets of ASD symptoms. PMID:25089229

  12. A catalog of hemizygous variation in 127 22q11 deletion patients.

    PubMed

    Hestand, Matthew S; Nowakowska, Beata A; Vergaelen, Elfi; Van Houdt, Jeroen; Dehaspe, Luc; Suhl, Joshua A; Del-Favero, Jurgen; Mortier, Geert; Zackai, Elaine; Swillen, Ann; Devriendt, Koenraad; Gur, Raquel E; McDonald-McGinn, Donna M; Warren, Stephen T; Emanuel, Beverly S; Vermeesch, Joris R

    2016-01-01

    The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype.

  13. Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia.

    PubMed

    Bassett, J K; Chandler, K E; Douzgou, S

    2016-08-01

    Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS.

  14. Practical guidelines for managing adults with 22q11.2 deletion syndrome

    PubMed Central

    Fung, Wai Lun Alan; Butcher, Nancy J.; Costain, Gregory; Andrade, Danielle M.; Boot, Erik; Chow, Eva W.C.; Chung, Brian; Cytrynbaum, Cheryl; Faghfoury, Hanna; Fishman, Leona; García-Miñaúr, Sixto; George, Susan; Lang, Anthony E.; Repetto, Gabriela; Shugar, Andrea; Silversides, Candice; Swillen, Ann; van Amelsvoort, Therese; McDonald-McGinn, Donna M.; Bassett, Anne S.

    2015-01-01

    22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities. PMID:25569435

  15. Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia.

    PubMed

    Bassett, J K; Chandler, K E; Douzgou, S

    2016-08-01

    Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS. PMID:27184501

  16. Prevalence and Nature of Hearing Loss in 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Van Eynde, Charlotte; Swillen, Ann; Lambeens, Elien; Verhaert, Nicolas; Desloovere, Christian; Luts, Heleen; Vander Poorten, Vincent; Devriendt, Koenraad; Hens, Greet

    2016-01-01

    Purpose: The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome. Method: Extensive audiological measurements were conducted in 40 persons with proven 22q11.2 deletion (aged 6-36 years). Besides air and bone conduction thresholds in the frequency range between 0.125…

  17. The development of cognitive control in children with chromosome 22q11.2 deletion syndrome

    PubMed Central

    Shapiro, Heather M.; Tassone, Flora; Choudhary, Nimrah S.; Simon, Tony J.

    2014-01-01

    Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children (TD) were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular assays were also conducted in order to examine genotype of catechol-O-methyltransferase (COMT), a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning (as measured by full-scale IQ). When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures. PMID:24959159

  18. The Neuropsychology of 22q11 Deletion Syndrome. A Neuropsychiatric Study of 100 Individuals

    ERIC Educational Resources Information Center

    Niklasson, Lena; Gillberg, Christopher

    2010-01-01

    The primary objective of this study was to study the impact of ASD/ADHD on general intellectual ability and profile, executive functions and visuo-motor skills in children and adults with 22q11 deletion syndrome (22q11DS). A secondary aim was to study if gender, age, heart disease, ASD, ADHD or ASD in combination with ADHD had an impact on general…

  19. Recurrence risk figures for isolated tetralogy of Fallot after screening for 22q11 microdeletion.

    PubMed Central

    Digilio, M C; Marino, B; Giannotti, A; Toscano, A; Dallapiccola, B

    1997-01-01

    Isolated tetralogy of Fallot (TF) has a multifactorial mode of inheritance in most cases, and recurrence risk rates of 2.5-3% have been attributed to first degree relatives of an affected child. In a subgroup of patients with a strong family history, the transmission of a monogenic trait has been suspected. Microdeletion 22q11 (del(22q11)) can cause TF in the setting of DiGeorge and velocardiofacial syndromes, and has also been related to familial conotruncal cardiac defects. Empirical risk figures in families after exclusion of del(22q11) have never been calculated. We have investigated the overall occurrence of congenital heart defect (CHD) in relatives of 102 patients with isolated non-syndromic TF previously screened for del(22q11). Our results show that the frequency of CHD is 3% in sibs, 0.5% in parents, 0.3% in grandparents, 0.2% in uncles or aunts, and 0.6% in first cousins. The recurrence risk rate for sibs in our series is the same as that previously estimated, indicating that after exclusion of patients with del(22q11) genetic counselling to patients with isolated TF should not be modified. A high concordance rate among our affected sibs has been documented. Gene(s) different from those located on chromosome 22q11 must be involved in causing familial aggregation of non-syndromic TF in these cases. Images PMID:9132487

  20. Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects.

    PubMed

    Lv, Wei; Wang, Shuyu

    2014-11-01

    Chromosomal abnormalities and the 22q11 microdeletion are implicated in congenital heart defects (CHDs). This study was designed to detect these abnormalities in fetuses and determine the effect of genetic factors on CHD etiology. Between January 2010 and December 2011, 113 fetuses with CHD treated at the Beijing Obstetrics and Gynecology Hospital were investigated, using chromosome karyotyping of either amniotic fluid cell or umbilical cord blood cell samples. Fetuses with a normal result were then investigated for the 22q11 microdeletion by fluorescence in situ hybridization. Of the 113 patients, 12 (10.6%) exhibited chromosomal abnormalities, while 6 (5.3%) of the remaining 101 cases presented with a 22q11 microdeletion. The incidence of chromosomal abnormalities was significantly higher in the group of fetuses presenting with extracardiac malformations in addition to CHD (P<0.001), although the detection of the 22q11 microdeletion was not significantly different between the two groups (P=0.583). In addition, all fetuses with the 22q11 microdeletion occurred de novo. In conclusion, genetic factors are important in the etiology of CHD. Where fetuses present with cardiac defects, additional chromosomal analysis is required to detect extracardiac abnormalities. Fetuses with heart defects should also be considered for 22q11 microdeletion detection to evaluate fetal prognosis, particularly prior to surgery.

  1. Communication of Psychiatric Risk in 22q11.2 Deletion Syndrome: A Pilot Project.

    PubMed

    Hart, Sarah J; Schoch, Kelly; Shashi, Vandana; Callanan, Nancy

    2016-02-01

    Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an increased chance of developing a psychiatric disorder. While parents of children affected by 22q11.2DS typically receive counseling about risk for non-psychiatric health concerns, genetic counselors may be reluctant to discuss psychiatric risk. Further education of genetic counselors may be necessary to encourage discussion of psychiatric risk with these families. The goal of this project was to develop recommendations for genetic counselors to provide psychiatric risk information to families affected by 22q11.2DS. The recommendations were developed by synthesizing resources in the literature about risk communication. These recommendations were refined following an online focus group meeting with five health care professionals who were recruited for participation from 22q11.2DS clinics across the U.S.A. The focus group data revealed three themes related to discussion of psychiatric risk: 1) Stepwise approach, 2) Discussing treatment options and reducing risks, and 3) Addressing stigma. These recommendations may be used as a foundation for a future clinical protocol to encourage discussion about the risk for psychiatric illness at an earlier point in the diagnostic process for 22q11.2DS and to provide improved information, support and resources to affected families. PMID:26578232

  2. Chromosome 22q11.2 deletion syndrome in African-American patients: a diagnostic challenge.

    PubMed

    Veerapandiyan, Aravindhan; Abdul-Rahman, Omar A; Adam, Margaret P; Lyons, Michael J; Manning, Melanie; Coleman, Karlene; Kobrynski, Lisa; Taneja, Deeksha; Schoch, Kelly; Zimmerman, Holly H; Shashi, Vandana

    2011-09-01

    Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features. A previous report highlighted the under-diagnosis of this condition in African Americans, thought to be related to a paucity of typical facial features. We ascertained the largest cohort (n = 50) of African-American individuals with 22q11DS reported thus far, across five genetics centers in the United States and report on their facial and other phenotypic features. About 3/4 of our cohort has at least one dysmorphic facial feature. Auricular abnormalities, especially small ears, are the most common dysmorphic facial feature followed by nasal and ocular abnormalities. Skeletal findings are seen in about 2/3 of our cohort, higher than the typical frequency reported in 22q11DS. Cardiac anomalies, developmental delay, and palatal abnormalities are seen at a lower frequency in our cohort. Thus, it is evident that the features traditionally associated with 22q11DS are difficult to recognize in African-American individuals with this syndrome, due to both altered frequencies of major anomalies and a non-classic facial appearance. Therefore, a high index of suspicion is needed to recognize 22q11DS in African-American individuals. PMID:21834039

  3. Maladaptive Conflict Monitoring as Evidence for Executive Dysfunction in Children with Chromosome 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Bish, Joel P.; Ferrante, Samantha M.; McDonald-McGinn, Donna; Zackai, Elaine; Simon, Tony J.

    2005-01-01

    Using an adaptation of the Attentional Networks Test, we investigated aspects of executive control in children with chromosome 22q11.2 deletion syndrome (DS22q11.2), a common but not well understood disorder that produces non-verbal cognitive deficits and a marked incidence of psychopathology. The data revealed that children with DS22q11.2…

  4. Eye Gaze During Face Processing in Children and Adolescents with 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Glaser, Bronwyn; Debbane, Martin; Ottet, Marie-Christine; Vuilleumier, Patrik; Zesiger, Pascal; Antonarakis, Stylianos E.; Eliez, Stephan

    2010-01-01

    Objective: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic syndrome with high risk for the development of psychiatric disorder. There is interest in identifying reliable markers for measuring and monitoring socio-emotional impairments in 22q11DS during development. The current study investigated eye gaze as a potential marker during a…

  5. The use of two different MLPA kits in 22q11.2 deletion syndrome.

    PubMed

    Evers, L J M; Engelen, J J M; Houben, L M H; Curfs, L M G; van Amelsvoort, T A M J

    2016-04-01

    22q11.2 deletion syndrome (22q11DS) is one of the most common recurrent copy-number variant disorder, caused by a microdeletion in chromosome band 22q11.2 and occurring with a population prevalence of 1 in 2000. Until today there has been no evidence that the size of the deletion has an influence on the clinical phenotype. Most studies report that 22q11DS is associated with mild or borderline intellectual disability. There are a limited number of reports on 22q11DS subjects with moderate or severe intellectual disability. In this study we describe 63 adult patients with 22q11DS, including 22q11DS patients functioning at a moderate to severe intellectual disabled level. Deletion size was established with an experimental Multiplex ligation-dependent probe amplification (MLPA) mixture (P324) in addition to the commonly used MLPA kit (P250). We compared deletion size with intellectual functioning and presence of psychotic symptoms during life. The use of the experimental MLPA kit gives extra information on deletion size, only when combined with the common MLPA kit. We were able to detect eleven atypical deletions and in two cases the deletion size was shorter than all other "typical ones". We conclude that the use of the experimental kit P324 gives extra information about the deletion size, but only when used together with the standard P250 kit. We did not found any relation of deletion size with intelligence or presence of psychosis. PMID:26921528

  6. Are 22q11.2 distal deletions associated with math difficulties?

    PubMed

    Carvalho, Maria Raquel Santos; Vianna, Gabrielle; Oliveira, Lívia de Fátima Silva; Costa, Annelise Julio; Pinheiro-Chagas, Pedro; Sturzenecker, Rosane; Zen, Paulo Ricardo Gazzola; Rosa, Rafael Fabiano Machado; de Aguiar, Marcos José Burle; Haase, Vitor Geraldi

    2014-09-01

    Approximately 6% of school-aged children have math difficulties (MD). A neurogenetic etiology has been suggested due to the presence of MD in some genetic syndromes such as 22q11.2DS. However, the contribution of 22q11.2DS to the MD phenotype has not yet been investigated. This is the first population-based study measuring the frequency of 22q11.2DS among school children with MD. Children (1,564) were identified in the schools through a screening test for language and math. Of these children, 152 (82 with MD and 70 controls) were selected for intelligence, general neuropsychological, and math cognitive assessments and for 22q11.2 microdeletion screening using MLPA. One child in the MD group had a 22q11.2 deletion spanning the LCR22-4 to LCR22-5 interval. This child was an 11-year-old girl with subtle anomalies, normal intelligence, MD attributable to number sense deficit, and difficulties in social interactions. Only 19 patients have been reported with this deletion. Upon reviewing these reports, we were able to characterize a new syndrome, 22q11.2 DS (LCR22-4 to LCR22-5), characterized by prematurity; pre- and postnatal growth restriction; apparent hypotelorism, short/upslanting palpebral fissures; hypoplastic nasal alae; pointed chin and nose; posteriorly rotated ears; congenital heart defects; skeletal abnormalities; developmental delay, particularly compromising the speech; learning disability (including MD, in one child); intellectual disability; and behavioral problems. These results suggest that 22q11.2 DS (LCR22-4 to LCR22-5) may be one of the genetic causes of MD.

  7. 22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis

    PubMed Central

    Squarcione, Chiara; Torti, Maria Chiara; Di Fabio, Fabio; Biondi, Massimo

    2013-01-01

    The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%–2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome. PMID:24353423

  8. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome

    PubMed Central

    Mlynarski, Elisabeth E.; Xie, Michael; Taylor, Deanne; Sheridan, Molly B.; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Chow, Eva W. C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S.; Morrow, Bernice E.

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60–75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients. PMID:26742502

  9. Neuroimaging correlates of 22q11.2 deletion syndrome: implications for schizophrenia research.

    PubMed

    Boot, E; van Amelsvoort, T A M J

    2012-01-01

    22q11.2 Deletion syndrome (22q11DS) is the most common known recurrent copy-number variant disorder. It is also the most common known genetic risk factor for schizophrenia. The greater homogeneity of subjects with schizophrenia in 22q11DS compared with schizophrenia in the wider non-deleted population may help to identify much needed information on neuroanatomical substrates, and neurochemical and neurofunctional mechanisms that may modulate the risk for schizophrenia. Identification of the underlying pathophysiology creates opportunities for developing genotype-specific, biology-based and targeted treatments to prevent, delay or minimize the severity of schizophrenia in both 22q11DS and the wider non-deleted population. This article reviews neuroimaging studies that focused on brain structure and function in this high-risk population, with particular attention to schizophrenia research. We also discuss the evidence on the role of candidate genes within the 22q11.2 region, with particular reference to catechol-O-methyl transferase (COMT) and proline dehydrogenase (PRODH). PMID:23279171

  10. Opitz GBBB syndrome and the 22q11.2 deletion

    SciTech Connect

    Lacassie, Y.; Arriaza, M.I.

    1996-03-29

    Recently, McDonald-McGinn et al. reported the presence of a deletion 22q11.2 in a family with autosomal dominant inheritance and in a sporadic case with the Opitz GBBB syndrome. The presence of a vascular ring in these patients prompted them to look for this deletion, since this anomaly may be associated with the 22q11.2 deletion. They reviewed the Opitz GBBB syndrome and the 22q11.2 microdeletion syndrome, finding considerable overlap of manifestations. They proposed that, in some patients, the Opitz GBBB syndrome may be due to a 22q11.2 deletion. We recently examined a newborn boy referred because of MCA. The cardinal findings in this patient (hypertelorism, hypospadias with descended testicles, characteristic nose and truncus arteriosus type I) were suggestive of the Opitz GBBB syndrome and of the velocardiofacial syndrome. The chromosomes were apparently normal (46,XY), but the FISH study showed a 22q11.2 deletion. The patient developed hypocalcemia with very low level of PTH and heart failure requiring surgery. His immunological status was normal except that CD4 cells were mildly low and natural killer cells were increased in number. The family history was noncontributory, but the full evaluation of the family is pending. The mother at first glance presents apparent hypertelorism. 3 refs.

  11. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size.

    PubMed

    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Varma, Binuja

    2012-01-01

    We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance with developmental delay but no other signs of the 22q11.2 microdeletion syndrome including cardiovascular malformation. The fluorescence in situ hybridization (FISH) analysis had shown a microdeletion on the chromosome 22q11.2 in both twins. The interphase FISH did not find any evidence for the mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip (Illumina), was identical between the twins except different size of deletion of 22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina) microarray analysis suggested monozygosity. This observation indicates that altered size of the deletion may be the underlying etiology for the discordance in phenotype in monozygotic twins. We think early post zygotic events (mitotic non-allelic homologous recombination) could have been played a role in the alteration of 22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins. PMID:22413934

  12. Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm.

    PubMed

    Schneider, Maude; Eliez, Stephan; Birr, Julie; Menghetti, Sarah; Debbané, Martin; Van der Linden, Martial

    2016-03-01

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive and functional impairments and increased risk for schizophrenia. We characterized multitasking abilities of adolescents with 22q11.2DS using an experimental naturalistic setting and examined whether multitasking impairments were associated with real-world functioning and negative symptoms. Thirty-nine adolescents (19 with 22q11.2DS and 20 controls) underwent the Multitasking Evaluation for Adolescents. Real-world functioning and clinical symptoms were assessed in participants with 22q11.2DS. Adolescents with 22q11.2DS performed poorly in the multitasking evaluation. Our data also suggest that multitasking abilities are related to adaptive functioning in the practical domain and negative symptoms. This study shows that adolescents with 22q11.2DS are characterized by multitasking impairments, which may be relevant for several aspects of the clinical phenotype. PMID:26914469

  13. Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm.

    PubMed

    Schneider, Maude; Eliez, Stephan; Birr, Julie; Menghetti, Sarah; Debbané, Martin; Van der Linden, Martial

    2016-03-01

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive and functional impairments and increased risk for schizophrenia. We characterized multitasking abilities of adolescents with 22q11.2DS using an experimental naturalistic setting and examined whether multitasking impairments were associated with real-world functioning and negative symptoms. Thirty-nine adolescents (19 with 22q11.2DS and 20 controls) underwent the Multitasking Evaluation for Adolescents. Real-world functioning and clinical symptoms were assessed in participants with 22q11.2DS. Adolescents with 22q11.2DS performed poorly in the multitasking evaluation. Our data also suggest that multitasking abilities are related to adaptive functioning in the practical domain and negative symptoms. This study shows that adolescents with 22q11.2DS are characterized by multitasking impairments, which may be relevant for several aspects of the clinical phenotype.

  14. A patient with 22q11.2 deletion syndrome: case report.

    PubMed

    Eryılmaz, Sema Kabataş; Baş, Firdevs; Satan, Ali; Darendeliler, Feyza; Bundak, Rüveyde; Günöz, Hülya; Saka, Nurçin

    2009-01-01

    22q11 deletion is one of the most frequently encountered genetic syndromes. The phenotypic spectrum shows a wide variability. We report a boy who presented at age 11.9 years with seizures due to hypocalcemia as a result of hypoparathyroidism. FISH analysis revealed a heterozygote deletion at 22q11.2. Positive findings for the syndrome were delayed speech development due to velofacial dysfunction, recurrent croup attacks in early childhood due to latent hypocalcemia and mild dysmorphic features. The findings of this patient indicate that 22q11 deletion syndrome may present with a wide spectrum of clinical findings and that this diagnosis needs to be considered even in patients of older ages presenting with hypocalcemia.

  15. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    PubMed

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.

  16. ESOPHAGEAL ATRESIA WITH RECURRENT TRACHEOESOPHAGEAL FISTULAS AND MICRODUPLICATION 22q11.23.

    PubMed

    Puvabanditsin, S; Garrow, E; February, M; Yen, E; Mehta, R

    2015-01-01

    The microduplication 22q11.2 syndrome has a wide range of clinical manifestations. The phenotype ranges from normal to mental retardation and congenital anomalies. Esophageal atresia/tracheoesophageal fistula (EA/TEF) has recently been linked with the Tbx1 gene mutation located on the long arm of chromosome 22(22q11.21). We report a case with 1.4 Mb 22q11.23 duplication detected by array-CGH. The father of this infant has the same interstitial microduplication but with a normal phenotype. The phenotype seen in our case is type C (3B) esophageal atresia, tracheoesophageal fistula, and ventricular septal defect. Our patient underwent primary repair of OA/TEF malformations, which was later complicated by pneumonia and a recurrent TEF. PMID:26625662

  17. Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.

    PubMed

    Cascella, Marco; Muzio, Maria Rosaria

    2015-01-01

    Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. PMID:26358864

  18. Hypoparathyroidism as the major manifestation in two patients with 22q11 deletions

    SciTech Connect

    Scire, G.; Bonaiuto, F.; Galasso, C.; Boscherini, B.; Dallapiccola, B.; Mingarelli, R.; Iannetti, P.

    1994-10-01

    We report on two adolescents with 22q11 deletion. Their main clinical manifestation was chronic symptomatic hypocalcemia secondary to hypoparathyroidism, together with seizures and cerebral calcifications. Neither congenital cardiac abnormality nor T cell deficiency were detected. The phenotypic manifestations of the observed patients were consistent with velo-cardiofacial syndrome (VCFS). A microdeletion of chromosome region 22q11 has been demonstrated in approximately 90% of DiGeorge syndrome (DGS) patients and in 75% of VCFS patients; the association of the deletion with a wide spectrum of clinical findings suggests the existence of a contiguous gene syndrome. The presence of certain traits of DGS/VCFS should lead to investigations of parathtroid function and molecular analysis of the 22q11 region hybridization studies. 10 refs., 5 figs., 2 tabs.

  19. A patient with 22q11.2 deletion syndrome: case report.

    PubMed

    Eryılmaz, Sema Kabataş; Baş, Firdevs; Satan, Ali; Darendeliler, Feyza; Bundak, Rüveyde; Günöz, Hülya; Saka, Nurçin

    2009-01-01

    22q11 deletion is one of the most frequently encountered genetic syndromes. The phenotypic spectrum shows a wide variability. We report a boy who presented at age 11.9 years with seizures due to hypocalcemia as a result of hypoparathyroidism. FISH analysis revealed a heterozygote deletion at 22q11.2. Positive findings for the syndrome were delayed speech development due to velofacial dysfunction, recurrent croup attacks in early childhood due to latent hypocalcemia and mild dysmorphic features. The findings of this patient indicate that 22q11 deletion syndrome may present with a wide spectrum of clinical findings and that this diagnosis needs to be considered even in patients of older ages presenting with hypocalcemia. PMID:21274400

  20. Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

    PubMed

    Fuchs, Jennifer C; Zinnamon, Fhatarah A; Taylor, Ruth R; Ivins, Sarah; Scambler, Peter J; Forge, Andrew; Tucker, Abigail S; Linden, Jennifer F

    2013-01-01

    22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM. PMID:24244619

  1. Behavioral phenotype in children with 22q11DS: agreement between parents and teachers.

    PubMed

    Klaassen, Petra W J; Duijff, Sasja N; Sinnema, Gerben; Beemer, Frits A; Swanenburg de Veye, Henriëtte F N; Vorstman, Jacob A S

    2015-03-01

    Patients with the 22q11-deletion syndrome (22q11DS) are at an increased risk of developing schizophrenia. Besides the effects of genetic variation, environmental factors could also be important in modifying the risk of schizophrenia in 22q11DS patients. In particular, previous studies have shown the importance of stress as a precipitating factor of psychosis. An incongruence between the perceived and actual severity of behavioral and cognitive domains could lead caregivers, and even the children themselves, to make demands that are insufficiently adapted to the child's abilities, causing stress and anxiety. Here, we investigate whether such diagnostic discrepancies are indeed present by comparing parent and teacher reports on behavioral concerns in children with 22q11DS. Behavioral questionnaires (CBCL and TRF) were prepared for both parents and teachers of 146 children with 22q11DS. We found that in line with previous reports, internalizing behavior was more frequently reported than externalizing behavior. While the behavioral profiles reported by parents and teachers were remarkably similar, the teachers' ratings were significantly lower (Total problem score p = .002). Age and IQ were not significantly associated with the severity of reported concerns. Our results indicate that indeed a disparity often exists between parents' and teachers' perceptions of the severity of a child's behavioral deficits. This may result in (substantially) different demands and expectations being placed on the child from the two fronts. We speculate that the stress resulting from this lack of cohesion between parents and teachers could precipitate, at least in some 22q11DS children, the emergence of psychosis.

  2. Hearing loss in a mouse model of 22q11.2 Deletion Syndrome.

    PubMed

    Fuchs, Jennifer C; Zinnamon, Fhatarah A; Taylor, Ruth R; Ivins, Sarah; Scambler, Peter J; Forge, Andrew; Tucker, Abigail S; Linden, Jennifer F

    2013-01-01

    22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM.

  3. Hearing Loss in a Mouse Model of 22q11.2 Deletion Syndrome

    PubMed Central

    Fuchs, Jennifer C.; Zinnamon, Fhatarah A.; Taylor, Ruth R.; Ivins, Sarah; Scambler, Peter J.; Forge, Andrew; Tucker, Abigail S.; Linden, Jennifer F.

    2013-01-01

    22q11.2 Deletion Syndrome (22q11DS) arises from an interstitial chromosomal microdeletion encompassing at least 30 genes. This disorder is one of the most significant known cytogenetic risk factors for schizophrenia, and can also cause heart abnormalities, cognitive deficits, hearing difficulties, and a variety of other medical problems. The Df1/+ hemizygous knockout mouse, a model for human 22q11DS, recapitulates many of the deficits observed in the human syndrome including heart defects, impaired memory, and abnormal auditory sensorimotor gating. Here we show that Df1/+ mice, like human 22q11DS patients, have substantial rates of hearing loss arising from chronic middle ear infection. Auditory brainstem response (ABR) measurements revealed significant elevation of click-response thresholds in 48% of Df1/+ mice, often in only one ear. Anatomical and histological analysis of the middle ear demonstrated no gross structural abnormalities, but frequent signs of otitis media (OM, chronic inflammation of the middle ear), including excessive effusion and thickened mucosa. In mice for which both in vivo ABR thresholds and post mortem middle-ear histology were obtained, the severity of signs of OM correlated directly with the level of hearing impairment. These results suggest that abnormal auditory sensorimotor gating previously reported in mouse models of 22q11DS could arise from abnormalities in auditory processing. Furthermore, the findings indicate that Df1/+ mice are an excellent model for increased risk of OM in human 22q11DS patients. Given the frequently monaural nature of OM in Df1/+ mice, these animals could also be a powerful tool for investigating the interplay between genetic and environmental causes of OM. PMID:24244619

  4. Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome

    SciTech Connect

    Fryburg, J.S.; Lin, K.Y.; Golden, W.L.

    1996-03-29

    This report is on a 14-month-old boy with manifestations of Opitz (G/BBB) syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested because of some findings in this patient reminiscent of velocardiofacial (VCF) syndrome. The extent of aspiration and of respiratory symptoms in this child is not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one on Xp, the other on 22q11.2. 12 refs., 2 figs.

  5. 22q11.2 deletion carriers and schizophrenia-associated novel variants.

    PubMed

    Balan, S; Iwayama, Y; Toyota, T; Toyoshima, M; Maekawa, M; Yoshikawa, T

    2014-01-01

    The penetrance of schizophrenia risk in carriers of the 22q11.2 deletion is high but incomplete, suggesting the possibility of additional genetic defects. We performed whole exome sequencing on two individuals with 22q11.2 deletion, one with schizophrenia and the other who was psychosis-free. The results revealed novel genetic variants related to neuronal function exclusively in the person with schizophrenia (frameshift: KAT8, APOH and SNX31; nonsense: EFCAB11 and CLVS2). This study paves the way towards a more complete understanding of variant dose and genetic architecture in schizophrenia. PMID:24482440

  6. Acute Dystonia in a Patient with 22q11.2 Deletion Syndrome

    PubMed Central

    Kontoangelos, Konstantinos; Maillis, Antonis; Maltezou, Maria; Tsiori, Sofia; Papageorgiou, Charalambos C.

    2015-01-01

    The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders. The clinical features of the syndrome are distinct facial appearance, velopharyngeal insufficiency, conotruncal heart disease, parathyroid and immune dysfunction; however, little is known about possible neurodegenerative diseases. We describe the case of an 18-year old patient suffering from 22q11.2 deletion syndrome. Since adolescence, he presented with behavioral disorders, recommended treatment with 2 mg aloperidin and he presented cervical dystonia and emergence of torticollis and trunk dystonia. Antipsychotic medications either accelerate or reveal dystonic symptoms. PMID:26605035

  7. Analysis of 22q11.2 deletions by FISH in a series of velocardiofacial syndrome patients

    SciTech Connect

    Ravnan, J.B.; Golabi, M.; Lebo, R.V.

    1994-09-01

    Deletions in chromosome 22 band q11.2 have been associated with velocardiofacial (VCF or Shprintzen) syndrome and the DiGeorge anomaly. A study of VCF patients evaluated at the UCSF Medical Center was undertaken to correlate disease phenotype with presence or absence of a deletion. Patients referred for this study had at least two of the following: dysmorphic facial features, frequent ear infections or hearing loss, palate abnormalities, thymic hypoplasia, hypocalcemia, congenital heart defect, hypotonia, and growth or language delay. Fluorescence in situ hybridization (FISH) using the DiGeorge critical region probe N25 was used to classify patients according to the presence or absence of a deletion in 22q11.2, and the results were compared to clinical characteristics. We have completed studies on 58 patients with features of VCF. Twenty-one patients (36%) were found to have a deletion in 22q11.2 by FISH. A retrospective study of archived slides from 14 patients originally studied only by prometaphase GTG banding found six patients had a deletion detected by FISH; of these, only two had a microscopically visible chromosome deletion. Our study of 11 sets of parents of children with the deletion found two clinically affected mothers with the deletion, including one with three of three children clinically affected. A few patients who did not fit the classical VCF description had a 22q11.2 deletion detected by FISH. These included one patient with both cleft lip and palate, and another with developmental delay and typical facial features but no cardiac or palate abnormalities. Both patients with the DiGeorge anomaly as part of VCF had the deletion. On the other hand, a number of patients diagnosed clinically with classical VCF did not have a detectable deletion. This raises the question whether they represent a subset of patients with a defect of 22q11.2 not detected by the N25 probe, or whether they represent a phenocopy of VCF.

  8. Mapping Cortical Morphology in Youth with Velocardiofacial (22q11.2 Deletion) Syndrome

    ERIC Educational Resources Information Center

    Kates, Wendy R.; Bansal, Ravi; Fremont, Wanda; Antshel, Kevin M.; Hao, Xuejun; Higgins, Anne Marie; Liu, Jun; Shprintzen, Robert J.; Peterson, Bradley S.

    2011-01-01

    Objective: Velocardiofacial syndrome (VCFS; 22q11.2 deletion syndrome) represents one of the highest known risk factors for schizophrenia. Insofar as up to 30% of individuals with this genetic disorder develop schizophrenia, VCFS constitutes a unique, etiologically homogeneous model for understanding the pathogenesis of schizophrenia. Method:…

  9. Microsatellite DNA markers detects 95% of chromosome 22q11 deletions

    SciTech Connect

    Bonnet, D.; Cormier-Daire, V.; Munnich, A.; Lyonnet, S.

    1997-01-20

    Cono-truncal cardiac malformations account for some 50% of congenital heart defects in newborn infants. Recently, hemizygosity for chromosome 22q11.2 was reported in patients with the DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) and causally related disorders. We have explored the potential use of microsatellite DNA markers for rapid detection of 22q11 deletions in 19 newborn infants referred for cono-truncal heart malformations with associated DGS/VCFS anomalies. A failure of parental inheritance was documented in 84.2% of cases (16/19). PCR-based genotyping using microsatellite DNA markers located within the commonly deleted region allowed us either to confirm or reject a 22q11 microdeletion in 94.3% of cases (18/19) within 24 hours. This test is now currently performed in the infants referred to us for a cono-truncal heart malformation as a first intention screening for 22q11 microdeletion. 10 refs., 1 fig., 1 tab.

  10. [Analysis of microdeletions in 22q11 in Colombian patients with congenital heart disease].

    PubMed

    Salazar, Marleny; Villalba, Guiovanny; Mateus, Heidi; Villegas, Victoria; Fonseca, Dora; Núñez, Federico; Caicedo, Víctor; Pachón, Sonia; Bernal, Jaime E

    2011-12-01

    Cardiac defects are the most frequent congenital malformations, with an incidence estimated between 4 and 12 per 1000 newborns. Their etiology is multifactorial and might be attributed to genetic predispositions and environmental factors. Since 1990 these types of pathologies have been associated with 22q11 microdeletion. In this study, the frequency of microdeletion 22q11 was determined in 61 patients with non-syndromic congenital heart disease. DNA was extracted from peripheral blood and TUPLE1 and STR D10S2198 genes were amplified by multiplex PCR and visualized in agarose gels. Gene content was quantified by densitometry. Three patients were found with microdeletion 22q11, representing a 4.9% frequency. This microdeletion was associated with two cases of Tetralogy of Fallot and a third case with atrial septal defect (ASD). In conclusion, the frequency for microdeletion 22q11 in the population analyzed was 4.9%. The cases that presented Teratology of Fallot had a frequency for this microdeletion of 7.4% and for ASD of 11.1%.

  11. Prodromal and autistic symptoms in schizotypal personality disorder and 22q11.2 deletion syndrome.

    PubMed

    Esterberg, Michelle L; Ousley, Opal Y; Cubells, Joseph F; Walker, Elaine F

    2013-02-01

    Despite clear diagnostic distinctions, schizophrenia and autism share symptoms on several dimensions. Recent research has suggested the two disorders overlap in etiology, particularly with respect to inherited and noninherited genetic factors. Studying the relationship between psychotic-like and autistic-like symptoms in risk groups such as 22q11 deletion syndrome (22q11DS) and schizotypal personality disorder (SPD) has the potential to shed light on such etiologic factors; thus, the current study examined prodromal symptoms and autistic features in samples of 22q11DS and SPD subjects using standardized diagnostic measures, including the Structured Interview for Prodromal Symptoms (SIPS) and the Autism Diagnostic Inventory-Revised (ADI-R). Results showed that SPD subjects manifested significantly more severe childhood and current social as well as stereotypic autistic features, as well as more severe positive prodromal symptoms. The two groups did not differ on negative, disorganized, or general prodromal symptoms, but were distinguishable based on correlations between prodromal and autistic features; the relationships between childhood autistic features and current prodromal symptoms were stronger for the SPD group. The results suggest that childhood autistic features are less continuous with subsequent prodromal signs in 22q11DS patients relative to those with SPD, and the findings highlight the importance of studying the overlap in diagnostic phenomenology in groups at risk for developing psychosis and/or autism.

  12. Functional outcomes of adults with 22q11.2 deletion syndrome

    PubMed Central

    Butcher, Nancy J.; Chow, Eva W.C.; Costain, Gregory; Karas, Dominique; Ho, Andrew; Bassett, Anne S.

    2012-01-01

    Purpose The 22q11.2 deletion syndrome is a common multisystem genomic disorder with congenital and later-onset manifestations, including congenital heart disease, intellectual disability, and psychiatric illness, that may affect long-term functioning. There are limited data on adult functioning in 22q11.2 deletion syndrome. Methods We used the Vineland Adaptive Behavior Scales to assess functioning in 100 adults with 22q11.2 deletion syndrome (n = 46 male; mean age = 28.8 (standard deviation = 9.7) years) where intellect ranged from average to borderline (n = 57) to mild intellectual disability (n = 43). Results More than 75% of the subjects scored in the functional deficit range. Although personal, vocational, and financial demographics confirmed widespread functional impairment, daily living skills and employment were relative strengths. Intelligence quotient was a significant predictor (P < 0.001) of overall and domain-specific adaptive functioning skills. A diagnosis of schizophrenia was a significant predictor (P < 0.05) of overall adaptive functioning, daily living skills, and socialization scores. Notably, congenital heart disease, history of mood/anxiety disorders, sex, and age were not significant predictors of functioning. Conclusion Despite functional impairment in adulthood that is primarily mediated by cognitive and psychiatric phenotypes, relative strengths in activities of daily living and employment have important implications for services and long-term planning. These results may help to inform expectations about outcomes for patients with 22q11.2 deletion syndrome. PMID:22744446

  13. Core Neuropsychological Characteristics of Children and Adolescents with 22q11.2 Deletion

    ERIC Educational Resources Information Center

    Jacobson, C.; Shearer, J.; Habel, A.; Kane, F.; Tsakanikos, E.; Kravariti, E.

    2010-01-01

    Background: The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological…

  14. Domain Specific Attentional Impairments in Children with Chromosome 22Q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Bish, Joel P.; Chiodo, Renee; Mattei, Victoria; Simon, Tony J.

    2007-01-01

    One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of…

  15. Hippocampal Malrotation is Associated with Chromosome 22q11.2 Microdeletion

    PubMed Central

    Andrade, Danielle M.; Krings, Timo; Chow, Eva W.C.; Kiehl, Tim-Rasmus; Bassett, Anne S.

    2015-01-01

    Background Patients with chromosome 22q11.2 deletion syndrome (22q11DS) are at a seven fold increased risk of developing seizures. However, only a fraction of these patients exhibit structural abnormalities such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH) that are known to cause seizures and to be associated with 22q11DS. In this study we used a dedicated seizure imaging protocol to look for additional structural abnormalities in these individuals that may explain the elevated risk of seizure disorder in this patient group. Methods Nineteen consecutive adult subjects with 22q11DS underwent a 3 Tesla MRI with a dedicated high-resolution seizure protocol. Neurological exam was performed in all patients. Genome-wide analysis excluded the presence of other pathogenic microdeletions or duplications. Results Structural abnormalities were found in 11 of 14 subjects with sufficient image quality. These included three patients with PNH, one of whom had associated PMG. In addition, there was a surprisingly high prevalence of unilateral hippocampal malrotation (HIMAL), observed in 9 of 14 cases (64%). EEG findings showed interictal epileptiform discharges with focal distribution in four patients and generalized discharges in one patient. Conclusion The results suggest that, in addition to other known structural abnormalities, 22q11DS is associated with HIMAL. It has been suggested that this developmental abnormality of the hippocampus may predispose or otherwise contribute to epileptogenesis. However in this study we observed HIMAL in a large proportion of patients, with and without epilepsy. Therefore, other as yet unknown factors may contribute to the high prevalence of epilepsy in this population. PMID:23968937

  16. Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

    PubMed Central

    Schneider, Maude; Armando, Marco; Pontillo, Maria; Vicari, Stefano; Debbané, Martin; Schultze‐Lutter, Frauke; Eliez, Stephan

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio‐demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 ± 17.6 months after initial assessment. Eighty‐nine participants with 22q11DS (age range: 8‐30 years; mean 16.1 ± 4.7) were assessed using the Structured Interview for Psychosis‐Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non‐UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high‐risk samples. Nevertheless, the relatively high transition rate in non‐UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.

  17. Velopharyngeal Anatomy in 22q11.2 Deletion Syndrome: A Three-Dimensional Cephalometric Analysis

    PubMed Central

    Ruotolo, Rachel A.; Veitia, Nestor A.; Corbin, Aaron; McDonough, Joseph; Solot, Cynthia B.; McDonald-McGinn, Donna; Zackai, Elaine H.; Emanuel, Beverly S.; Cnaan, Avital; LaRossa, Don; Arens, Raanan; Kirschner, Richard E.

    2010-01-01

    Objective 22q11.2 deletion syndrome is the most common genetic cause of velopharyngeal dysfunction (VPD). Magnetic resonance imaging (MRI) is a promising method for noninvasive, three-dimensional (3D) assessment of velopharyngeal (VP) anatomy. The purpose of this study was to assess VP structure in patients with 22q11.2 deletion syndrome by using 3D MRI analysis. Design This was a retrospective analysis of magnetic resonance images obtained in patients with VPD associated with a 22q11.2 deletion compared with a normal control group. Setting This study was conducted at The Children’s Hospital of Philadelphia, a pediatric tertiary care center. Patients, Participants The study group consisted of 5 children between the ages of 2.9 and 7.9 years, with 22q11.2 deletion syndrome confirmed by fluorescence in situ hybridization analysis. All had VPD confirmed by nasendoscopy or videofluoroscopy. The control population consisted of 123 unaffected patients who underwent MRI for reasons other than VP assessment. Interventions Axial and sagittal T1- and T2-weighted magnetic resonance images with 3-mm slice thickness were obtained from the orbit to the larynx in all patients by using a 1.5T Siemens Visions system. Outcome Measures Linear, angular, and volumetric measurements of VP structures were obtained from the magnetic resonance images with VIDA image- processing software. Results The study group demonstrated greater anterior and posterior cranial base and atlanto-dental angles. They also demonstrated greater pharyngeal cavity volume and width and lesser tonsillar and adenoid volumes. Conclusion Patients with a 22q11.2 deletion demonstrate significant alterations in VP anatomy that may contribute to VPD. PMID:16854203

  18. Platybasia in 22q11.2 Deletion Syndrome Is Not Correlated with Speech Resonance

    PubMed Central

    Kon, Moshe; Mink van der Molen, Aebele B

    2014-01-01

    Background An abnormally obtuse cranial base angle, also known as platybasia, is a common finding in patients with 22q11.2 deletion syndrome (22q11DS). Platybasia increases the depth of the velopharynx and is therefore postulated to contribute to velopharyngeal dysfunction. Our objective was to determine the clinical significance of platybasia in 22q11DS by exploring the relationship between cranial base angles and speech resonance. Methods In this retrospective chart review at a tertiary hospital, 24 children (age, 4.0-13.1 years) with 22q11.2DS underwent speech assessments and lateral cephalograms, which allowed for the measurement of the cranial base angles. Results One patient (4%) had hyponasal resonance, 8 (33%) had normal resonance, 10 (42%) had hypernasal resonance on vowels only, and 5 (21%) had hypernasal resonance on both vowels and consonants. The mean cranial base angle was 136.5° (standard deviation, 5.3°; range, 122.3-144.8°). The Kruskal-Wallis test showed no significant relationship between the resonance ratings and cranial base angles (P=0.242). Cranial base angles and speech ratings were not correlated (Spearman correlation=0.321, P=0.126). The group with hypernasal resonance had a significantly more obtuse mean cranial base angle (138° vs. 134°, P=0.049) but did not have a greater prevalence of platybasia (73% vs. 56%, P=0.412). Conclusions In this retrospective chart review of patients with 22q11DS, cranial base angles were not correlated with speech resonance. The clinical significance of platybasia remains unknown. PMID:25075355

  19. Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

    PubMed Central

    Schneider, Maude; Armando, Marco; Pontillo, Maria; Vicari, Stefano; Debbané, Martin; Schultze‐Lutter, Frauke; Eliez, Stephan

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio‐demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 ± 17.6 months after initial assessment. Eighty‐nine participants with 22q11DS (age range: 8‐30 years; mean 16.1 ± 4.7) were assessed using the Structured Interview for Psychosis‐Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non‐UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high‐risk samples. Nevertheless, the relatively high transition rate in non‐UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth. PMID:27717277

  20. Visual scanpath abnormalities in 22q11.2 deletion syndrome: is this a face specific deficit?

    PubMed

    McCabe, Kathryn; Rich, Dominique; Loughland, Carmel Maree; Schall, Ulrich; Campbell, Linda Elisabet

    2011-09-30

    People with 22q11.2 deletion syndrome (22q11DS) have deficits in face emotion recognition. However, it is not known whether this is a deficit specific to faces, or represents maladaptive information processing strategies to complex stimuli in general. This study examined the specificity of face emotion processing deficits in 22q11DS by exploring recognition accuracy and visual scanpath performance to a Faces task compared to a Weather Scene task. Seventeen adolescents with 22q11DS (11=females, age=17.4) and 18 healthy controls (11=females, age=17.7) participated in the study. People with 22q11DS displayed an overall impoverished scanning strategy to face and weather stimuli alike, resulting in poorer accuracy across all stimuli for the 22q11DS participants compared to controls. While the control subjects altered their information processing in response to faces, a similar change was not present in the 22q11DS group indicating different visual scanpath strategies to identify category within each of the tasks, of which faces appear to represent a particularly difficult subcategory. To conclude, while this study indicates that people with 22q11DS have a general visual processing deficit, the lack of strategic change between tasks suggest that the 22q11DS group did not adapt to the change in stimuli content as well as the controls, indicative of cognitive inflexibility rather than a face specific deficit. PMID:21831452

  1. Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome

    PubMed Central

    Nilsson, Simon RO.; Fejgin, Kim; Gastambide, Francois; Vogt, Miriam A.; Kent, Brianne A.; Nielsen, Vibeke; Nielsen, Jacob; Gass, Peter; Robbins, Trevor W.; Saksida, Lisa M.; Stensbøl, Tine B.; Tricklebank, Mark D.; Didriksen, Michael; Bussey, Timothy J.

    2016-01-01

    A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus – within the current protocols – the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional “hits” being required for phenotypic expression. PMID:27507786

  2. Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome.

    PubMed

    Nilsson, Simon Ro; Fejgin, Kim; Gastambide, Francois; Vogt, Miriam A; Kent, Brianne A; Nielsen, Vibeke; Nielsen, Jacob; Gass, Peter; Robbins, Trevor W; Saksida, Lisa M; Stensbøl, Tine B; Tricklebank, Mark D; Didriksen, Michael; Bussey, Timothy J

    2016-10-01

    A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus - within the current protocols - the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional "hits" being required for phenotypic expression.

  3. An Fgf8 Mouse Mutant Phenocopies Human 22q11 Deletion Syndrome

    PubMed Central

    Frank, Deborah U.; Fotheringham, Lori K.; Brewer, Judson A.; Muglia, Louis J.; Tristani-Firouzi, Martin; Capecchi, Mario R.; Moon, Anne M.

    2006-01-01

    SUMMARY Deletion of chromosome 22q11, the most common microdeletion detected in humans, is associated with a life-threatening array of birth defects. Although 90% of affected individuals share the same three megabase deletion, their phenotype is highly variable and includes craniofacial and cardiovascular anomalies, hypoplasia or aplasia of the thymus with associated deficiency of T cells, hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of central nervous system abnormalities. Because ablation of neural crest in chicks produces many features of the deletion 22q11 syndrome, it has been proposed that haploinsufficiency in this region impacts neural crest function during cardiac and pharyngeal arch development. Few factors required for migration, survival, proliferation and subsequent differentiation of pharyngeal arch neural crest and mesoderm-derived mesenchyme into their respective cardiovascular, musculoskeletal, and glandular derivatives have been identified. However, the importance of epithelial-mesenchymal interactions and pharyngeal endoderm function is becoming increasingly clear. Fibroblast growth factor 8 is a signaling molecule expressed in the ectoderm and endoderm of the developing pharyngeal arches and known to play an important role in survival and patterning of first arch tissues. We demonstrate a dosage-sensitive requirement for FGF8 during development of pharyngeal arch, pharyngeal pouch and neural crest-derived tissues. We show that FGF8 deficient embryos have lethal malformations of the cardiac outflow tract, great vessels and heart due, at least in part, to failure to form the fourth pharyngeal arch arteries, altered expression of Fgf10 in the pharyngeal mesenchyme, and abnormal apoptosis in pharyngeal and cardiac neural crest. The Fgf8 mutants described herein display the complete array of cardiovascular, glandular and craniofacial phenotypes seen in human deletion 22q11 syndromes. This represents the first single gene

  4. Velo-cardio-facial syndrome: Frequency and textent of 22q11 deletions

    SciTech Connect

    Lindsay, E.A.; Goldberg, R.; Jurecic, V.

    1995-07-03

    Velo-cardio-facial (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phenotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH). In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions. 22 refs., 2 figs., 1 tab.

  5. Metyrosine in psychosis associated with 22q11.2 deletion syndrome: case report.

    PubMed

    Carandang, Carlo G; Scholten, Monique C

    2007-02-01

    This report describes the use of metyrosine (Demser) in an adolescent male with psychosis associated with the 22q11.2 deletion syndrome (velocardiofacial syndrome; VCFS), diagnosed by fluorescence in situ hybridization (FISH). He presented with multiple features of 22q11.2 deletion syndrome, including ventricular septal defect, palatal abnormalities, speech and motor delays, attention deficits, mood lability, and psychosis. After a failed trial of an atypical antipsychotic to address the psychosis, metyrosine was initiated, with significant reduction of psychotic symptoms and mood lability. Metyrosine treatment allowed this youth to live at home and to attend school, after months of recurrent psychiatric hospitalizations. The successful treatment of metyrosine for psychosis associated with VCFS represents a first in psychiatry, where a known biochemical abnormality in a psychiatric disorder was corrected by a treatment that targets the biochemical pathway, leading to reduction of psychiatric symptoms and improvement of functioning.

  6. Clinical Features of 78 Adults With 22q11 Deletion Syndrome

    PubMed Central

    Bassett, Anne S.; Chow, Eva W.C.; Husted, Janice; Weksberg, Rosanna; Caluseriu, Oana; Webb, Gary D.; Gatzoulis, Michael A.

    2011-01-01

    22q11 Deletion Syndrome (22q11DS) is a common microdeletion syndrome with multisystem expression. Phenotypic features vary with age, ascertainment, and assessment. We systematically assessed 78 adults (36 M, 42 F; mean age 31.5, SD 10.5 years) with a 22q11.2 deletion ascertained through an adult congenital cardiac clinic (n = 35), psychiatric-related sources (n = 39), or as affected parents of subjects (n = 4). We recorded the lifetime prevalence of features requiring attention, with 95% confidence intervals (CI) not overlapping zero. Subtle learning difficulties, hypernasality and facial gestalt were not included. We investigated ascertainment effects using non-overlapping subgroups ascertained with tetralogy of Fallot (n = 31) or schizophrenia (n = 31). Forty-three features met inclusion criteria and were present in 5% or more patients, including several of later onset (e.g., hypothyroidism, cholelithiasis). Number of features per patient (median 9, range 3–22) correlated with hospitalizations (P=0.0002) and, when congenital features were excluded, with age (P=0.02). Adjusting for ascertainment, 25.8% (95% CI, 9.5–42.1%) of patients had cardiac anomalies and 22.6% (95% CI, 7.0–38.2%) had schizophrenia. Ascertainment subgroups were otherwise similar in median number and prevalence of features. Non-characteristic features are common in 22q11DS. Adjusting for ascertainment effects is important. Many treatable conditions may be anticipated and features may accumulate over time. The results have implications for clinical assessment and management, genetic counseling and research into pathophysiological mechanisms. PMID:16208694

  7. Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association.

    PubMed Central

    Verloes, A; Curry, C; Jamar, M; Herens, C; O'Lague, P; Marks, J; Sarda, P; Blanchet, P

    1998-01-01

    Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder. Images PMID:9832043

  8. A Longitudinal Examination of the Psychoeducational, Neurocognitive, and Psychiatric Functioning in Children with 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Hooper, Stephen R.; Curtiss, Kathleen; Schoch, Kelly; Keshavan, Matcheri S.; Allen, Andrew; Shashi, Vandana

    2013-01-01

    The present study sought to examine the longitudinal psychoeducational, neurocognitive, and psychiatric outcomes of children and adolescents with chromosome 22q11.2 deletion syndrome (22q11DS), a population with a high incidence of major psychiatric illnesses appearing in late adolescence/early adulthood. Little is known of the developmental…

  9. The 22Q11.2 Deletion in Children: High Rate of Autistic Disorders and Early Onset of Psychotic Symptoms

    ERIC Educational Resources Information Center

    Vorstman, Jacob A. S.; Morcus, Monique E. J.; Duijff, Sasja N.; Klaassen, Petra W. J.; Heineman-de, Josien A.; Beemer, Frits A.; Swaab, Hanna; Kahn, Rene S.; van Engeland, Herman

    2006-01-01

    Objective: To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS). Method: Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric…

  10. Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome.

    PubMed

    Jonas, Rachel K; Jalbrzikowski, Maria; Montojo, Caroline A; Patel, Arati; Kushan, Leila; Chow, Carolyn C; Vesagas, Therese; Bearden, Carrie E

    2015-12-01

    22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.

  11. Social Skills and Associated Psychopathology in Children with Chromosome 22q11.2 Deletion Syndrome: Implications for Interventions

    ERIC Educational Resources Information Center

    Shashi, V.; Veerapandiyan, A.; Schoch, K.; Kwapil, T.; Keshavan, M.; Ip, E.; Hooper, S.

    2012-01-01

    Background: Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well-characterised. Objective: To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and…

  12. Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis.

    PubMed

    Scariati, Elisa; Schaer, Marie; Karahanoglu, Isik; Schneider, Maude; Richiardi, Jonas; Debbané, Martin; Van De Ville, Dimitri; Eliez, Stephan

    2016-09-01

    The 22q11.2 deletion syndrome (22q11DS) is associated with cognitive impairments and a 41% risk of developing schizophrenia. While several studies performed on patients with 22q11DS showed the presence of abnormal functional connectivity in this syndrome, how these alterations affect large-scale network organization is still unknown. Here we performed a network modularity analysis on whole-brain functional connectomes derived from the resting-state fMRI of 40 patients with 22q11DS and 41 healthy control participants, aged between 9 and 30 years old. We then split the sample at 18 years old to obtain two age subgroups and repeated the modularity analyses. We found alterations of modular communities affecting the visuo-spatial network and the anterior cingulate cortex (ACC) in both age groups. These results corroborate previous structural and functional studies in 22q11DS that showed early impairment of visuo-spatial processing regions. Furthermore, as ACC has been linked to the development of psychotic symptoms in 22q11DS, the early impairment of its functional connectivity provide further support that ACC alterations may provide potential biomarkers for an increased risk of schizophrenia. Finally, we found an abnormal modularity partition of the dorsolateral prefrontal cortex (DLPFC) only in adults with 22q11DS, suggesting the presence of an abnormal development of functional network communities during adolescence in 22q11DS. PMID:27371790

  13. Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome.

    PubMed

    Jonas, Rachel K; Jalbrzikowski, Maria; Montojo, Caroline A; Patel, Arati; Kushan, Leila; Chow, Carolyn C; Vesagas, Therese; Bearden, Carrie E

    2015-12-01

    22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure. PMID:27606315

  14. An interictal schizophrenia-like psychosis in an adult patient with 22q11.2 deletion syndrome

    PubMed Central

    Tastuzawa, Yasutaka; Sekinaka, Kanako; Suda, Tetsufumi; Matsumoto, Hiroshi; Otabe, Hiroyuki; Nonoyama, Shigeaki; Yoshino, Aihide

    2015-01-01

    In addition to causing polymalformative syndrome, 22q11.2 deletion can lead to various neuropsychiatric disorders including mental retardation, psychosis, and epilepsy. However, few reports regarding epilepsy-related psychosis in 22q11.2 deletion syndrome (22q11.2DS) exist. We describe the clinical characteristics and course of 22q11.2DS in a Japanese patient with comorbid mild mental retardation, childhood-onset localization-related epilepsy, and adult-onset, interictal schizophrenia-like psychosis. From a diagnostic viewpoint, early detection of impaired intellectual functioning and hyperprolinemia in patients with epilepsy with 22q11.2DS may be helpful in predicting the developmental timing of interictal psychosis. From a therapeutic viewpoint, special attention needs to be paid to phenytoin-induced hypocalcemia in this syndrome. PMID:25870791

  15. Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome

    PubMed Central

    Chan, Chrystal; Costain, Gregory; Ogura, Lucas; Silversides, Candice K.; Chow, Eva W.C.

    2015-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. Survival to reproductive age and beyond is now the norm. Several manifestations of this syndrome, such as congenital cardiac disease and neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in the general population. However, there are limited data on reproductive health in 22q11.2DS. We performed a retrospective chart review for 158 adults with 22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables relevant to pregnancy and reproductive health. We present four illustrative cases as brief vignettes. There were 25 adults (21>age 35 years; 21 female) with a history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared with expectations for the general population, showed a significantly elevated prevalence of small for gestational age liveborn offspring (p<0.001), associated mainly with infants with 22q11.2DS. Stillbirths also showed elevated prevalence (p<0.05). Not all observed adverse events appeared to be attributable to transmission of the 22q11.2 deletion. Recurring issues relevant to reproductive health in 22q11.2DS included the potential impact of maternal morbidities, inadequate social support, unsafe sexual practices, and delayed diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary results emphasize the importance of early diagnosis and long term follow-up that could help facilitate genetic counseling for men and women with 22q11.2DS. We propose initial recommendations for pre-conception management, educational strategies, pre-natal planning, and preparation for possible high-risk pregnancy and/or delivery. PMID:25579115

  16. An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

    PubMed Central

    Váša, František; Griffa, Alessandra; Scariati, Elisa; Schaer, Marie; Urben, Sébastien; Eliez, Stephan; Hagmann, Patric

    2015-01-01

    Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs — chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, “de-centralizing” the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30–40% of 22q11DS patients develop. PMID:26870660

  17. Behavioral and Psychiatric Phenotypes in 22q11.2 Deletion Syndrome

    PubMed Central

    Tang, Kerri L; Antshel, Kevin M; Fremont, Wanda P.

    2015-01-01

    22q11.2DS is a chromosomal microdeletion that affects approximately 40–50 genes, and impacts various organs and systems throughout the body. Detection is typically achieved by fluorescence in-situ hybridization following diagnosis of one of the major features of the deletion or via chromosomal microarray or non-invasive prenatal testing. The physical phenotype can include congenital heart defects, palatal and pharyngeal anomalies, hypocalcemia/hypoparathyroidism, skeletal abnormalities, and cranial/brain anomalies, although prevalence rates of all of these features are variable. Cognitive function is impaired to some degree in most individuals, with prevalence rates of greater than 90% for motor/speech delays and learning disabilities. Attention, executive function, working memory, visual spatial abilities, motor skills, and social cognition/social skills are affected. The deletion is also associated with an increased risk for behavioral disorders and psychiatric illness. The early onset of psychiatric symptoms common to 22q11.2DS disrupts the development and quality of life of individuals with the syndrome, and is also a potential risk factor for later development of a psychotic disorder. This review discusses prevalence, phenotypic features, and management of psychiatric disorders commonly diagnosed in children and adolescents with 22q11.2DS, including autism spectrum disorders, attention deficit/hyperactivity disorder, anxiety disorders, mood disorders, and schizophrenia/psychotic disorders. Guidelines for the clinical assessment and management of psychiatric disorders in youth with this syndrome are provided, as are treatment guidelines for the use of psychiatric medications. PMID:26372046

  18. Frontonasal malformation with tetralogy of Fallot associated with a submicroscopic deletion of 22q11

    SciTech Connect

    Stratton, R.F.; Payne, R.M.

    1997-03-31

    We report on a 14-month-old girl with bifid nasal tip and tetralogy of Fallot. Several similar patients have been described with CNS or eye abnormalities. Chromosome analysis with FISH, using Oncor DiGeorge probes, confirmed a submicroscopic deletion of 22q11. Many patients with Shprintzen (velo-cardio-facial) syndrome have a similar deletion with conotruncal cardiac defects and an abnormal nasal shape, suggesting that a gene in this area, possibly affecting neural crest cells, influences facial and other midline development. 13 refs., 1 fig.

  19. Potential Role of Cortisol in Social and Memory Impairments in Individuals with 22q11.2 Deletion Syndrome.

    PubMed

    Jacobson, Daniel; Bursch, Megan; Lajiness-O'Neill, Renee

    2016-09-01

    22q11.2 Deletion syndrome is a genetic disorder characterized by physiological and psychological symptoms. This study investigated the role of cortisol on the social and cognitive impairments in children with 22q11.2. A total of 11 children with 22q11.2 were assessed for baseline cortisol levels and received broad neuropsychological testing. Results were compared with 11 controls. Children with 22q11.2 had significantly higher cortisol levels. A significant negative correlation was observed between the general memory and attention/concentration indices of the Wide Range Assessment of Memory and Learning, 2nd edition and cortisol concentrations in the control population. These data provide evidence of a possible causal mechanism that underlies social impairments in stress disorders. PMID:27617156

  20. A case report of 22q11 deletion syndrome confirmed by array-CGH method

    PubMed Central

    Sedghi, Maryam; Nouri, Narges; Abdali, Hossein; Memarzadeh, Mehrdad; Nouri, Nayereh

    2012-01-01

    Velo-cardio-facial syndrome (VCFS) is caused by a submicroscopic deletion on the long arm of chromosome 22 and affects approximately 1 in 4000 persons, making it the second most prevalent genetic syndrome after Down syndrome and the most common genetic syndrome associated with cleft palate. Most of the 22q11.2 deletion cases are new occurrences or sporadic; however, in about 10 % of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. This report describes a 1.5 years-old male child with clinical signs of velo-cardio-facial syndrome (VCFS) presented with heart defect, soft cleft palate, developmental delay, acrocephaly, seizure, MRI abnormalities and descriptive facial feature, such as hypertelorism. Array-CGH test was done to confirm the diagnosis; the result revealed a 2.6 Mbp deletion in 22q11.2 chromosome that containing TBX1 and COMT genes. Our data suggest that haploinsufficiency of TBX1 gene is probably a major contributor to some of the syndrome characteristic signs, such as heart defect. Because of developmental delay and dysmorphic facial feature were observed in the index's mother and relatives, inherited autosomal dominant form of VCF is probable, and MLPA (multiplex ligation-dependent probe amplification) test should be performed for parents to estimate the recurrent risk in next pregnancy. PMID:23267387

  1. Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

    PubMed Central

    Philip, Nicole

    2011-01-01

    22q11.2 Deletion syndrome has become an important model for understanding the pathophysiology of neurodevelopmental conditions, particularly schizophrenia which develops in about 20–25% of individuals with a chromosome 22q11.2 microdeletion. From the initial discovery of the syndrome, associated developmental delays made it clear that changes in brain development were a key part of the expression. Once patients were followed through childhood into adult years, further neurobehavioural phenotypes became apparent, including a changing cognitive profile, anxiety disorders and seizure diathesis. The variability of expression is as wide as for the myriad physical features associated with the syndrome, with the addition of evolving phenotype over the developmental trajectory. Notably, variability appears unrelated to length of the associated deletion. Several mouse models of the deletion have been engineered and are beginning to reveal potential molecular mechanisms for the cognitive and behavioural phenotypes observable in animals. Both animal and human studies hold great promise for further discoveries relevant to neurodevelopment and associated cognitive, behavioural and psychiatric disorders. PMID:21573985

  2. 22q11.2 Deletion Syndrome: Laboratory Diagnosis and TBX1 and FGF8 Mutation Screening.

    PubMed

    Sgardioli, Ilária C; Vieira, Társis P; Simioni, Milena; Monteiro, Fabíola P; Gil-da-Silva-Lopes, Vera L

    2015-03-01

    Velocardiofacial syndrome is one of the recognized forms of chromosome 22q11.2 deletion syndrome (22q11.2 DS) and has an incidence of 1 of 4,000 to 1 of 6,000 births. Nevertheless, the 22q11 deletion is not found in several patients with a 22q11.2 DS phenotype. In this situation, other chromosomal aberrations and/or mutations in the T-box 1 transcription factor C (TBX1) gene have been detected in some patients. A similar phenotype to that of the 22q11.2 DS has been reported in animal models with mutations in fibroblast growth factor 8 (Fgf8) gene. To date, FGF8 mutations have not been investigated in humans. We tested a strategy to perform laboratory testing to reduce costs in the investigation of patients presenting with the 22q11.2 DS phenotype. A total of 109 individuals with clinical suspicion were investigated using GTG-banding karyotype, fluorescence in situ hybridization, and/or multiplex ligation-dependent probe amplification. A conclusive diagnosis was achieved in 33 of 109 (30.2%) cases. In addition, mutations in the coding regions of TBX1 and FGF8 genes were investigated in selected cases where 22q11.2 deletion had been excluded, and no pathogenic mutations were detected in both genes. This study presents a strategy for molecular genetic characterization of patients presenting with the 22q11.2 DS using different laboratory techniques. This strategy could be useful in different countries, according to local resources. Also, to our knowledge, this is the first investigation of FGF8 gene in humans with this clinical suspicion. PMID:27617111

  3. Intelligence and Visual Motor Integration in 5-Year-Old Children with 22q11-Deletion Syndrome

    ERIC Educational Resources Information Center

    Duijff, Sasja; Klaassen, Petra; Beemer, Frits; Swanenburg de Veye, Henriette; Vorstman, Jacob; Sinnema, Gerben

    2012-01-01

    The purpose of this study was to explore the relationship between intelligence and visual motor integration skills in 5-year-old children with 22q11-deletion syndrome (22q11DS) (N = 65, 43 females, 22 males; mean age 5.6 years (SD 0.2), range 5.23-5.99 years). Sufficient VMI skills seem a prerequisite for IQ testing. Since problems related to…

  4. 22q11.2 Deletion Syndrome: Laboratory Diagnosis and TBX1 and FGF8 Mutation Screening

    PubMed Central

    Sgardioli, Ilária C.; Vieira, Társis P.; Simioni, Milena; Monteiro, Fabíola P.; Gil-da-Silva-Lopes, Vera L.

    2015-01-01

    Velocardiofacial syndrome is one of the recognized forms of chromosome 22q11.2 deletion syndrome (22q11.2 DS) and has an incidence of 1 of 4,000 to 1 of 6,000 births. Nevertheless, the 22q11 deletion is not found in several patients with a 22q11.2 DS phenotype. In this situation, other chromosomal aberrations and/or mutations in the T-box 1 transcription factor C (TBX1) gene have been detected in some patients. A similar phenotype to that of the 22q11.2 DS has been reported in animal models with mutations in fibroblast growth factor 8 (Fgf8) gene. To date, FGF8 mutations have not been investigated in humans. We tested a strategy to perform laboratory testing to reduce costs in the investigation of patients presenting with the 22q11.2 DS phenotype. A total of 109 individuals with clinical suspicion were investigated using GTG-banding karyotype, fluorescence in situ hybridization, and/or multiplex ligation-dependent probe amplification. A conclusive diagnosis was achieved in 33 of 109 (30.2%) cases. In addition, mutations in the coding regions of TBX1 and FGF8 genes were investigated in selected cases where 22q11.2 deletion had been excluded, and no pathogenic mutations were detected in both genes. This study presents a strategy for molecular genetic characterization of patients presenting with the 22q11.2 DS using different laboratory techniques. This strategy could be useful in different countries, according to local resources. Also, to our knowledge, this is the first investigation of FGF8 gene in humans with this clinical suspicion. PMID:27617111

  5. Single nucleotide polymorphism discovery in TBX1 in individuals with and without 22q11.2 deletion syndrome

    PubMed Central

    Heike, Carrie L.; Starr, Jacqueline R.; Rieder, Mark J.; Cunningham, Michael L.; Edwards, Karen L.; Stanaway, Ian; Crawford, Dana C.

    2015-01-01

    BACKGROUND Children with 22q11.2 deletion syndrome (22q11.2DS) have a wide range of clinical features. TBX1 has been proposed as a candidate gene for some of the features in this condition. Polymorphisms in the non-deleted TBX1, which may affect the function of the sole TBX1 gene in individuals with the 22q11.2DS, may be a key to understanding the phenotypic variability among individuals with a shared deletion. Comprehensive single nucleotide polymorphism (SNP) discovery by resequencing candidate genes can identify genetic variants that influence a given phenotype. The purpose of this study was to further characterize the sequence variability in TBX1 by identifying all common SNPs in this gene. METHODS We resequenced TBX1 in 29 children with a documented 22q11.2 deletion and 95 non-deleted, healthy individuals. We estimated allele frequencies, performed tagSNP selection, and inferred haplotypes. We also compared SNP frequencies between 22q11.2DS and control samples. RESULTS We identified 355 biallelic markers among the 190 chromosomes resequenced in the control panel. The vast majority of the markers identified were SNPs (n=331), and the remainder indels (n=24). We did not identify SNPs or indels in the cis- regulatory element (FOX–binding site) upstream of TBX1. In children with 22q11.2DS we detected 187 biallelic markers, six of which were indels. Four of the seven coding SNPs identified in the controls were identified in children with 22q11.2DS. CONCLUSIONS This comprehensive SNP discovery data can be used to select SNPs to genotype for future association studies assessing the role of TBX1 and phenotypic variability in individuals with 22q11.2DS. PMID:19645056

  6. 22q11.2 Deletion Syndrome: Laboratory Diagnosis and TBX1 and FGF8 Mutation Screening

    PubMed Central

    Sgardioli, Ilária C.; Vieira, Társis P.; Simioni, Milena; Monteiro, Fabíola P.; Gil-da-Silva-Lopes, Vera L.

    2015-01-01

    Velocardiofacial syndrome is one of the recognized forms of chromosome 22q11.2 deletion syndrome (22q11.2 DS) and has an incidence of 1 of 4,000 to 1 of 6,000 births. Nevertheless, the 22q11 deletion is not found in several patients with a 22q11.2 DS phenotype. In this situation, other chromosomal aberrations and/or mutations in the T-box 1 transcription factor C (TBX1) gene have been detected in some patients. A similar phenotype to that of the 22q11.2 DS has been reported in animal models with mutations in fibroblast growth factor 8 (Fgf8) gene. To date, FGF8 mutations have not been investigated in humans. We tested a strategy to perform laboratory testing to reduce costs in the investigation of patients presenting with the 22q11.2 DS phenotype. A total of 109 individuals with clinical suspicion were investigated using GTG-banding karyotype, fluorescence in situ hybridization, and/or multiplex ligation-dependent probe amplification. A conclusive diagnosis was achieved in 33 of 109 (30.2%) cases. In addition, mutations in the coding regions of TBX1 and FGF8 genes were investigated in selected cases where 22q11.2 deletion had been excluded, and no pathogenic mutations were detected in both genes. This study presents a strategy for molecular genetic characterization of patients presenting with the 22q11.2 DS using different laboratory techniques. This strategy could be useful in different countries, according to local resources. Also, to our knowledge, this is the first investigation of FGF8 gene in humans with this clinical suspicion.

  7. Catechol-O-methyl Transferase and Expression of Schizophrenia in 73 Adults with 22q11 Deletion Syndrome

    PubMed Central

    Bassett, Anne S.; Caluseriu, Oana; Weksberg, Rosanna; Young, Donald A.; Chow, Eva W.C.

    2011-01-01

    Background Catechol-O-methyl transferase (COMT) is a candidate gene for schizophrenia with a role in dopamine metabolism, particularly in frontal cortex. COMT is within the region commonly deleted in 22q11 deletion syndrome (22q11DS), a syndrome with high prevalence of schizophrenia. We examined the role of COMT in schizophrenia-related expression in 22q11DS. Methods We genotyped the COMT functional Val158/108Met allele in 73 Caucasian adults with 22q11DS (36 men, 37 women; aged 33.8, SD 10.1 years; 37 Met, 36 Val hemizygosity) blind to clinical data and assessed effects on symptoms and frontal functioning. Results The lower activity Met allele was not significantly more prevalent than the Val allele in 33 subjects with schizophrenia. Excitement symptoms were more severe, however, and three frontal cognitive tests (theory of mind, Trails B, and olfactory identification), communication, and social functioning measures showed significantly worse performance with Met allele hemizygosity, even after accounting for effects of schizophrenia. Conclusions The results suggest that hemizygosity of the COMT functional allele exerts an effect on some measures of frontal functioning in 22q11DS. Elevated levels of tonic dopamine activation associated with the COMT Met allele may underlie these aspects of expression. We must look elsewhere for causes of the high prevalence of schizophrenia in 22q11DS, however. PMID:17217925

  8. Increased incidence and size of cavum septum pellicidum in children with chromosome 22q11.2 deletion syndrome

    PubMed Central

    Beaton, Elliott A.; Qin, Yufeng; Nguyen, Vy; Johnson, Joel; Pinter, Joseph D.; Simon, Tony J.

    2009-01-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a result of a hemizygotic microdeletion that results in a variety of impairments in children including greater risk for psychiatric ailments in adulthood. We used high-resolution magnetic resonance imaging to accurately quantify the length and, for the first time, volume, of cavum septum pellucidum (CSP) in children aged 7 to 14 years with 22q11.2DS and typically developing (TD) controls. Significantly greater anteroposterior length and greater CSP volumes were found in children with 22q11.2DS compared to controls. Furthermore, the largest CSP were found only in the 22q11.2DS group and with a much higher incidence than previously reported in the literature. Given the significant midline anomalies in the brains of those affected by 22q11.2DS, large CSP may be a biomarker of atypical brain development. The implication of these larger CSP for cognitive and behavioral development is a topic in need of further investigation. PMID:20074913

  9. Relationship between Reaction Time, Fine Motor Control, and Visual-Spatial Perception on Vigilance and Visual-Motor Tasks in 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Howley, Sarah A.; Prasad, Sarah E.; Pender, Niall P.; Murphy, Kieran C.

    2012-01-01

    22q11.2 Deletion Syndrome (22q11DS) is a common microdeletion disorder associated with mild to moderate intellectual disability and specific neurocognitive deficits, particularly in visual-motor and attentional abilities. Currently there is evidence that the visual-motor profile of 22q11DS is not entirely mediated by intellectual disability and…

  10. Performance on the Modified Card Sorting Test and Its Relation to Psychopathology in Adolescents and Young Adults with 22Q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Rockers, K.; Ousley, O.; Sutton, T.; Schoenberg, E.; Coleman, K.; Walker, E.; Cubells, J. F.

    2009-01-01

    Background: Approximately one-third of individuals with 22q11.2 deletion syndrome (22q11DS), a common genetic disorder highly associated with intellectual disabilities, may develop schizophrenia, likely preceded by a mild to moderate cognitive decline. Methods: We examined adolescents and young adults with 22q11DS for the presence of executive…

  11. Individuals with 22q11.2 Deletion Syndrome Are Impaired at Explicit, but Not Implicit, Discrimination of Local Forms Embedded in Global Structures

    ERIC Educational Resources Information Center

    Giersch, Anne; Glaser, Bronwyn; Pasca, Catherine; Chabloz, Mélanie; Debbané, Martin; Eliez, Stephan

    2014-01-01

    Individuals with 22q11.2 deletion syndrome (22q11.2DS) are impaired at exploring visual information in space; however, not much is known about visual form discrimination in the syndrome. Thirty-five individuals with 22q11.2DS and 41 controls completed a form discrimination task with global forms made up of local elements. Affected individuals…

  12. Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome

    ERIC Educational Resources Information Center

    Weisman, Omri; Feldman, Ruth; Burg-Malki, Merav; Keren, Miri; Geva, Ronny; Diesendruck, Gil; Gothelf, Doron

    2015-01-01

    Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with…

  13. A Comparative Study of Cognition and Brain Anatomy between Two Neurodevelopmental Disorders: 22q11.2 Deletion Syndrome and Williams Syndrome

    ERIC Educational Resources Information Center

    Campbell, Linda E.; Stevens, Angela; Daly, Eileen; Toal, Fiona; Azuma, Rayna; Karmiloff-Smith, Annette; Murphy, Declan G. M.; Murphy, Kieran C.

    2009-01-01

    Background: 22q11.2 deletion syndrome (22q11DS) is associated with intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies comparing cognition and neuroanatomical characteristics of 22q11DS with other syndromes to investigate if the cognitive strengths and difficulties and…

  14. Association of the Family Environment with Behavioural and Cognitive Outcomes in Children with Chromosome 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Allen, T. M.; Hersh, J.; Schoch, K.; Curtiss, K.; Hooper, S. R.; Shashi, V.

    2014-01-01

    Background: Children with 22q11.2 deletion syndrome (22q11DS) are at risk for social-behavioural and neurocognitive sequelae throughout development. The current study examined the impact of family environmental characteristics on social-behavioural and cognitive outcomes in this paediatric population. Method: Guardians of children with 22q11DS…

  15. De novo direct duplication of chromosome segment 22q11.2-q13.1

    SciTech Connect

    Fujimoto, Atsuko; Lin, Ming S.

    1996-03-29

    Lindsay et al. [1995] reported a case of de novo duplication of the segment 22q11-q12. Molecular cytogenetics studies showed that the segment includes the regions responsible for the {open_quotes}cat eye,{close_quotes} DiGeorge, and velo-cardio-facial syndrome, and extends distal to the breakpoint cluster region. The phenotype was milder than that of complete trisomy 22 and der(22)t(11;22) (q23;q11) syndrome and was similar in type and severity to that of {open_quotes}cat eye{close_quotes} syndrome (CES). They suggested that trisomy of gene(s) responsible for the CES might have a predominant phenotypic effect over other genes present in the region duplicated in their patient. 3 refs., 2 figs.

  16. Molecular Definition of the 22q11 Deletions in Velo-Cardio-Facial Syndrome

    PubMed Central

    Morrow, Bernice; Goldberg, Rosalie; Carlson, Christine; Gupta, Ruchira Das; Sirotkin, Howard; Collins, John; Dunham, Ian; O'Donnell, Hilary; Scambler, Peter; Shprintzen, Robert; Kucherlapati, Raju

    1995-01-01

    Velo-cardio-facial syndrome (VCFS) is a common genetic disorder among individuals with cleft palate and is associated with hemizygous deletions in human chromosome 22q11. Toward the molecular definition of the deletions, we constructed a physical map of 22q11 in the form of overlapping YACs. The physical map covers >9 cM of genetic distance, estimated to span 5 Mb of DNA, and contains a total of 64 markers. Eleven highly polymorphic short tandem-repeat polymorphic (STRP) markers were placed on the physical map, and 10 of these were unambiguously ordered. The 11 polymorphic markers were used to type the DNA from a total of 61 VCFS patients and 49 unaffected relatives. Comparison of levels of heterozygosity of these markers in VCFS patients and their unaffected relatives revealed that four of these markers are commonly hemizygous among VCFS patients. To confirm these results and to define further the breakpoints in VCFS patients, 15 VCFS individuals and their unaffected parents were genotyped for the 11 STRP markers. Haplotypes generated from this study revealed that 82% of the patients have deletions that can be defined by the STRP markers. The results revealed that all patients who have a deletion share a common proximal breakpoint, while there are two distinct distal breakpoints. Markers D22S941 and D22S944 appear to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. The results also show that the parental origin of the deleted chromosome does not have any effect on the phenotypic manifestation ImagesFigure 2Figure 3 PMID:7762562

  17. Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

    PubMed Central

    Grassi, Marcília S.; Jacob, Cristina M. A.; Kulikowski, Leslie D.; Pastorino, Antonio C.; Dutra, Roberta L.; Miura, Nana; Jatene, Marcelo B.; Pegler, Stephanie P.; Kim, Chong A.; Carneiro-Sampaio, Magda

    2014-01-01

    Background To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients. PMID:25317860

  18. Neural mechanisms of response inhibition and impulsivity in 22q11.2 deletion carriers and idiopathic attention deficit hyperactivity disorder.

    PubMed

    Montojo, C A; Congdon, E; Hwang, L; Jalbrzikowski, M; Kushan, L; Vesagas, T K; Jonas, R K; Ventura, J; Bilder, R M; Bearden, C E

    2015-01-01

    22q11DS offers a compelling model to understand the neural substrates of attentional dysfunction.•First study directly comparing neural function in 22q11DS vs. ADHD patients•22q11DS and ADHD patients show a shared deficit in RI-related activation.•ADHD patients showed greater activity in the middle frontal gyrus than 22q11DS during RI.•Neural activity is inversely correlated with self-reported Cognitive Impulsivity in 22q11DS. PMID:26509118

  19. Increased Levels of Interferon-Inducible Protein 10 (IP-10) in 22q11.2 Deletion Syndrome.

    PubMed

    Aresvik, D M; Lima, K; Øverland, T; Mollnes, T E; Abrahamsen, T G

    2016-03-01

    The 22q11.2 deletion syndrome (22q11.2 DS), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:4000 births. These patients may suffer from affection of many organ systems with cardiac malformations, thymic hypoplasia or aplasia, hypoparathyroidism, palate anomalies and psychiatric disorders being the most frequent. The incidence of autoimmune diseases is increased in older patients. The aim of the present study was to examine a cytokine profile in patients with 22q11.2 DS by measuring a broad spectrum of serum cytokines. Patients with a proven deletion of chromosome 22q11.2 (n = 55) and healthy individuals (n = 54) recruited from an age- and sex-comparable group were included in the study. Serum levels of 27 cytokines, including chemokines and growth factors, were analysed using multiplex technology. Interferon-inducible protein 10 (IP-10) was also measured by ELISA to confirm the multiplex results. The 22q11.2 DS patients had distinctly and significantly raised levels of pro-inflammatory and angiostatic chemokine IP-10 (P < 0.001) compared to controls. The patients with congenital heart defects (n = 31) had significantly (P = 0.018) raised serum levels of IP-10 compared to patients born without heart defects (n = 24). The other cytokines investigated were either not detectable or did not differ between patients and controls.

  20. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome.

    PubMed

    de la Morena, M Teresa; Eitson, Jennifer L; Dozmorov, Igor M; Belkaya, Serkan; Hoover, Ashley R; Anguiano, Esperanza; Pascual, M Virginia; van Oers, Nicolai S C

    2013-04-01

    Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance.

  1. A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients

    PubMed Central

    Widdershoven, Josine C.C.; Bowser, Mark; Sheridan, Molly B.; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Solot, Cynthia B.; Kirschner, Richard E.; Beemer, Frits A.; Morrow, Bernice E.; Devoto, Marcella; Emanuel, Beverly S.

    2014-01-01

    Objective Palatal anomalies are one of the identifying features of 22q11.2 deletion syndrome (22q11.2DS) affecting about one third of patients. To identify genetic variants that increase the risk of cleft or palatal anomalies in 22q11.2DS patients, we performed a candidate gene association study in 101 patients with 22q11.2DS genotyped with the Affymetrix genome-wide human SNP array 6.0. Methods Patients from Children's Hospital of Philadelphia, USA and Wilhelmina Children's Hospital Utrecht, The Netherlands were stratified based on palatal phenotype (overt cleft, submucosal cleft, bifid uvula). SNPs in 21 candidate genes for cleft palate were analyzed for genotype-phenotype association. In addition, TBX1 sequencing was carried out. Quality control and association analyses were conducted using the software package PLINK. Results Genotype and phenotype data of 101 unrelated patients (63 non-cleft subjects (62.4%), 38 cleft subjects (37.6%)) were analyzed. A Total of 39 SNPs on 10 genes demonstrated a p-value ≤0.05 prior to correction. The most significant SNPs were found on FGF10. However none of the SNPs remained significant after correcting for multiple testing. Conclusions Although these results are promising, analysis of additional samples will be required to confirm that variants in these regions influence risk for cleft palate or palatal anomalies in 22q11.2DS patients. PMID:23121717

  2. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome

    PubMed Central

    de la Morena, M. Teresa; Eitson, Jennifer L.; Dozmorov, Igor M.; Belkaya, Serkan; Hoover, Ashley R.; Anguiano, Esperanza; Pascual, M. Virginia; van Oers, Nicolai S.C.

    2013-01-01

    Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3 Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance. PMID:23454892

  3. Genetic Dosage Compensation in a Family with Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome

    PubMed Central

    Alkalay, Avishai A.; Guo, Tingwei; Montagna, Cristina; Digilio, M. Cristina; Marino, Bruno; Dallapiccola, Bruno; Morrow, Bernice

    2014-01-01

    Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome revealed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carries a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as revealed by fluorescence in situ hybridization and array comparative genome hybridization analysis. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for genetic counseling of future children. PMID:21337693

  4. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    PubMed Central

    Mok, Kin Y; Sheerin, Una; Simón-Sánchez, Javier; Salaka, Afnan; Chester, Lucy; Escott-Price, Valentina; Mantripragada, Kiran; Doherty, Karen M; Noyce, Alastair J; Mencacci, Niccolo E; Lubbe, Steven J; Williams-Gray, Caroline H; Barker, Roger A; van Dijk, Karin D; Berendse, Henk W; Heutink, Peter; Corvol, Jean-Christophe; Cormier, Florence; Lesage, Suzanne; Brice, Alexis; Brockmann, Kathrin; Schulte, Claudia; Gasser, Thomas; Foltynie, Thomas; Limousin, Patricia; Morrison, Karen E; Clarke, Carl E; Sawcer, Stephen; Warner, Tom T; Lees, Andrew J; Morris, Huw R; Nalls, Mike A; Singleton, Andrew B; Hardy, John; Abramov, Andrey Y; Plagnol, Vincent; Williams, Nigel M; Wood, Nicholas W

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0–55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5–61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). Interpretation Clinicians should be alert to the possibility of 22q11.2 deletions in

  5. Independent De Novo 22q11.2 Deletions in First Cousins With DiGeorge/Velocardiofacial Syndrome

    PubMed Central

    Saitta, Sulagna C.; Harris, Stacy E.; McDonald-McGinn, Donna M.; Emanuel, Beverly S.; Tonnesen, Melissa K.; Zackai, Elaine H.; Seitz, Suzanne C.; Driscoll, Deborah A.

    2010-01-01

    Deletions of chromosome 22q11.2 are found in the vast majority of patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion syndrome is estimated to occur in 1 in 4,000 live births. The majority of deletions are de novo, with 10% or less inherited from an affected parent. Here, we report two separate families with recurrence of a 22q11.2 deletion in first cousins. In each family, unaffected siblings (brother and sister) had an affected child. Fluorescence in situ hybridization (FISH) studies of the parents of each affected child were normal and hence, relatives were not considered at an increased risk for recurrence in another pregnancy. We used highly polymorphic microsatellite repeat markers from within 22q11.2 to determine the parental origin of each cousin’s deletion and to assess whether parental germline mosaicism for the 22q11.2 deletion might be a factor in these cases. This analysis confirmed that in each case, the deletion occurred on a chromosome 22 derived from unrelated parents, consistent with independent de novo deletion events. Thus, we concluded that germline mosaicism as the underlying mechanism for affected cousins in these families was unlikely. Our findings underscore the high frequency with which the 22q11.2 deletion occurs in the general population and demonstrate the important role that PCR-based parental origin determination can have in recurrence risk counselling. Furthermore, relatives of affected individuals may benefit from genetic counselling and consider prenatal testing for the 22q11.2 deletion in future pregnancies, despite a low recurrence risk. PMID:14708107

  6. Psychiatric Disorders From Childhood to Adulthood in 22q11.2 Deletion Syndrome: Results From the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome

    PubMed Central

    Schneider, Maude; Debbané, Martin; Bassett, Anne S.; Chow, Eva W.C.; Fung, Wai Lun Alan; van den Bree, Marianne B.M.; Owen, Michael; Murphy, Kieran C.; Niarchou, Maria; Kates, Wendy R.; Antshel, Kevin M.; Fremont, Wanda; McDonald-McGinn, Donna M.; Gur, Raquel E.; Zackai, Elaine H.; Vorstman, Jacob; Duijff, Sasja N.; Klaassen, Petra W.J.; Swillen, Ann; Gothelf, Doron; Green, Tamar; Weizman, Abraham; Van Amelsvoort, Therese; Evers, Laurens; Boot, Erik; Shashi, Vandana; Hooper, Stephen R.; Bearden, Carrie E.; Jalbrzikowski, Maria; Armando, Marco; Vicari, Stefano; Murphy, Declan G.; Ousley, Opal; Campbell, Linda E.; Simon, Tony J.; Eliez, Stephan

    2014-01-01

    Objective Chromosome 22q11.2 deletion syndrome is a neurogenetic disorder associated with high rates of schizophrenia and other psychiatric conditions. The authors report what is to their knowledge the first large-scale collaborative study of rates and sex distributions of psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome. The associations among psychopathology, intellect, and functioning were examined in a subgroup of participants. Method The 1,402 participants with 22q11.2 deletion syndrome, ages 6–68 years, were assessed for psychiatric disorders with validated diagnostic instruments. Data on intelligence and adaptive functioning were available for 183 participants ages 6 to 24 years. Results Attention deficit hyperactivity disorder (ADHD) was the most frequent disorder in children (37.10%) and was overrepresented in males. Anxiety disorders were more prevalent than mood disorders at all ages, but especially in children and adolescents. Anxiety and unipolar mood disorders were overrepresented in females. Psychotic disorders were present in 41% of adults over age 25. Males did not predominate in psychotic or autism spectrum disorders. Hierarchical regressions in the subgroup revealed that daily living skills were predicted by the presence of anxiety disorders. Psychopathology was not associated with communication or socialization skills. Conclusions To the authors' knowledge, this is the largest study of psychiatric morbidity in 22q11.2 deletion syndrome. It validates previous findings that this condition is one of the strongest risk factors for psychosis. Anxiety and developmental disorders were also prevalent. These results highlight the need to monitor and reduce the long-term burden of psychopathology in 22q11.2 deletion syndrome. PMID:24577245

  7. Isolation of a transcription factor expressed in neural crest from the region of 22q11 deleted in DiGeorge syndrome

    SciTech Connect

    Wadey, R.; Roberts, C.; Daw, S.

    1994-09-01

    Deletions within chromosome 22q11 cause a wide variety of birth defects including DiGeorge syndrome and Shprintzen syndrome. We have defined a commonly deleted region of over 2 Mb, and a critical region of 300 kb. A gene, TUPLE1, has been isolated from this critical region encoding a transcriptional regulator similar to the yeast HIR1 histone regulator gene. Since it has been suggested that DGS results from a defective neural crest, the expression of Tuple1 was examined in whole mouse and chick embryos, tissue sections and neural tube explants: Tuple1 is expressed in a dynamic pattern with high levels in regions containing migrating crest. Prior to crest migration Tuple1 is expressed in a rhombomere-specific expression pattern. Later Tuple1 is expressed in discrete domains within the developing neural tube. A remarkable feature of the experiments was the detection of a similar dynamic pattern with sense probe; i.e., there is an antisense Tuple1 transcript. This was confirmed using RPA. Tuple1 is being screened for mutations in non-deletion patients and constructs assembled for homologous recombination in ES cells. Tuple1 maps to MMU16 extending the homology of linkage with human chromosome 22. From these data we predict that the human homologue of the murine scid mutation maps to 22q11.

  8. Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome.

    PubMed

    Merico, Daniele; Zarrei, Mehdi; Costain, Gregory; Ogura, Lucas; Alipanahi, Babak; Gazzellone, Matthew J; Butcher, Nancy J; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Chow, Eva W C; Andrade, Danielle M; Frey, Brendan J; Marshall, Christian R; Scherer, Stephen W; Bassett, Anne S

    2015-11-01

    Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes. PMID:26384369

  9. Overlapping Numerical Cognition Impairments in Children with Chromosome 22q11.2 Deletion or Turner Syndromes

    ERIC Educational Resources Information Center

    Simon, T. J.; Takarae, Y.; DeBoer, T.; McDonald-McGinn, D. M.; Zackai, E. H.; Ross, J. L.

    2008-01-01

    Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor…

  10. SDF1-CXCR4 signaling: A new player involved in DiGeorge/22q11-deletion syndrome.

    PubMed

    Duband, Jean-Loup; Escot, Sophie; Fournier-Thibault, Claire

    2016-01-01

    The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial syndrome, is a congenital disease causing numerous structural and behavioral disorders, including cardiac outflow tract anomalies, craniofacial dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It results from a unique chromosomal microdeletion on the 22q11.2 region in which the transcriptional activator TBX1 is decisive for the occurrence of the disease. During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving rise to structures of the face, neck and chest. Genetic and developmental studies demonstrated that the severity and variability of the syndrome are determined by Tbx1 targets involved in pharyngeal neural crest cell migration and survival. Recently, we demonstrated that the chemokine Sdf1/Cxcl12 and its receptor Cxcr4 are genetically downstream of Tbx1 during pharyngeal development and that reduction of CXCR4 signaling results in defects which recapitulate the major morphological anomalies of 22q11DS, supporting the possibility of a pivotal role for the SDF1/CXCR4 axis in its etiology. PMID:27500073

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

    ERIC Educational Resources Information Center

    Kates, Wendy R.; Krauss, Beth R.; AbdulSabur, Nuria; Colgan, Deirdre; Antshel, Kevin M.; Higgins, Anne Marie; Shprintzen, Robert J.

    2007-01-01

    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…

  12. Memory in Intellectually Matched Groups of Young Participants with 22q11.2 Deletion Syndrome and Those with Schizophrenia

    ERIC Educational Resources Information Center

    Kravariti, Eugenia; Jacobson, Clare; Morris, Robin; Frangou, Sophia; Murray, Robin M.; Tsakanikos, Elias; Habel, Alex; Shearer, Jo

    2010-01-01

    The 22q11.2 deletion syndrome (22qDS) and schizophrenia have genetic and neuropsychological similarities, but are likely to differ in memory profile. Confirming differences in memory function between the two disorders, and identifying their genetic determinants, can help to define genetic subtypes in both syndromes, identify genetic risk factors…

  13. Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome

    PubMed Central

    Merico, Daniele; Zarrei, Mehdi; Costain, Gregory; Ogura, Lucas; Alipanahi, Babak; Gazzellone, Matthew J.; Butcher, Nancy J.; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Chow, Eva W. C.; Andrade, Danielle M.; Frey, Brendan J.; Marshall, Christian R.; Scherer, Stephen W.; Bassett, Anne S.

    2015-01-01

    Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes. PMID:26384369

  14. SDF1-CXCR4 signaling: A new player involved in DiGeorge/22q11-deletion syndrome

    PubMed Central

    Duband, Jean-Loup; Escot, Sophie; Fournier-Thibault, Claire

    2016-01-01

    ABSTRACT The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial syndrome, is a congenital disease causing numerous structural and behavioral disorders, including cardiac outflow tract anomalies, craniofacial dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It results from a unique chromosomal microdeletion on the 22q11.2 region in which the transcriptional activator TBX1 is decisive for the occurrence of the disease. During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving rise to structures of the face, neck and chest. Genetic and developmental studies demonstrated that the severity and variability of the syndrome are determined by Tbx1 targets involved in pharyngeal neural crest cell migration and survival. Recently, we demonstrated that the chemokine Sdf1/Cxcl12 and its receptor Cxcr4 are genetically downstream of Tbx1 during pharyngeal development and that reduction of CXCR4 signaling results in defects which recapitulate the major morphological anomalies of 22q11DS, supporting the possibility of a pivotal role for the SDF1/CXCR4 axis in its etiology. PMID:27500073

  15. Whole-Genome Sequencing Suggests Schizophrenia Risk Mechanisms in Humans with 22q11.2 Deletion Syndrome.

    PubMed

    Merico, Daniele; Zarrei, Mehdi; Costain, Gregory; Ogura, Lucas; Alipanahi, Babak; Gazzellone, Matthew J; Butcher, Nancy J; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Chow, Eva W C; Andrade, Danielle M; Frey, Brendan J; Marshall, Christian R; Scherer, Stephen W; Bassett, Anne S

    2015-09-16

    Chromosome 22q11.2 microdeletions impart a high but incomplete risk for schizophrenia. Possible mechanisms include genome-wide effects of DGCR8 haploinsufficiency. In a proof-of-principle study to assess the power of this model, we used high-quality, whole-genome sequencing of nine individuals with 22q11.2 deletions and extreme phenotypes (schizophrenia, or no psychotic disorder at age >50 years). The schizophrenia group had a greater burden of rare, damaging variants impacting protein-coding neurofunctional genes, including genes involved in neuron projection (nominal P = 0.02, joint burden of three variant types). Variants in the intact 22q11.2 region were not major contributors. Restricting to genes affected by a DGCR8 mechanism tended to amplify between-group differences. Damaging variants in highly conserved long intergenic noncoding RNA genes also were enriched in the schizophrenia group (nominal P = 0.04). The findings support the 22q11.2 deletion model as a threshold-lowering first hit for schizophrenia risk. If applied to a larger and thus better-powered cohort, this appears to be a promising approach to identify genome-wide rare variants in coding and noncoding sequence that perturb gene networks relevant to idiopathic schizophrenia. Similarly designed studies exploiting genetic models may prove useful to help delineate the genetic architecture of other complex phenotypes.

  16. Discussing the psychiatric manifestations of 22q11.2 deletion syndrome: an exploration of clinical practice among medical geneticists

    PubMed Central

    Morris, Emily; Inglis, Angela; Friedman, Jan; Austin, Jehannine

    2013-01-01

    Purpose The aim of this study was to determine the frequency with which medical geneticists discuss the psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) with families in relation to the frequency with which they discuss the other manifestations of the syndrome and to explore relationships between discussion of these features and stigma toward psychiatric disorders. Methods We surveyed medical geneticists in the United States and Canada regarding the frequency with which they discuss various features of 22q11DS with families in the context of four clinical scenarios in which only the age of the patient at diagnosis differed. Respondents also completed a 20-item validated psychometric measure of stigma towards psychiatric disorders. Results 308/546 medical geneticists completed the survey (56% response rate). Psychiatric disorders were discussed significantly less often than other features of 22q11DS (p<0.0001), but psychiatric disorders were discussed significantly more often when the patient was ≥ 13 years old (p<0.0001), than when the patient was younger. Geneticists who discussed psychiatric disorders the least had significantly higher levels of stigma towards psychiatric disorders (p=0.007). Conclusion Psychiatric risks are less often discussed with families during childhood. Education for physicians to help reduce stigma towards psychiatric disorders (which may impede discussion of psychiatric disorders) may warrant exploration in this population. PMID:23579435

  17. A defect in early myogenesis causes Otitis media in two mouse models of 22q11.2 Deletion Syndrome

    PubMed Central

    Fuchs, Jennifer C.; Linden, Jennifer F.; Baldini, Antonio; Tucker, Abigail S.

    2015-01-01

    Otitis media (OM), the inflammation of the middle ear, is the most common disease and cause for surgery in infants worldwide. Chronic Otitis media with effusion (OME) often leads to conductive hearing loss and is a common feature of a number of craniofacial syndromes, such as 22q11.2 Deletion Syndrome (22q11.2DS). OM is more common in children because the more horizontal position of the Eustachian tube (ET) in infants limits or delays clearance of middle ear effusions. Some mouse models with OM have shown alterations in the morphology and angle of the ET. Here, we present a novel mechanism in which OM is caused not by a defect in the ET itself but in the muscles that control its function. Our results show that in two mouse models of 22q11.2DS (Df1/+ and Tbx1+/−) presenting with bi- or unilateral OME, the fourth pharyngeal arch-derived levator veli palatini muscles were hypoplastic, which was associated with an earlier altered pattern of MyoD expression. Importantly, in mice with unilateral OME, the side with the inflammation was associated with significantly smaller muscles than the contralateral unaffected ear. Functional tests examining ET patency confirmed a reduced clearing ability in the heterozygous mice. Our findings are also of clinical relevance as targeting hypoplastic muscles might present a novel preventative measure for reducing the high rates of OM in 22q11.2DS patients. PMID:25452432

  18. Secondary Immunologic Consequences in Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

    PubMed Central

    Zemble, R.; Prak, E. Luning; McDonald, K.; McDonald-McGinn, D.; Zackai, E.; Sullivan, K.

    2010-01-01

    Clinical evidence suggests that patients with Chromosome 22q11.2 deletion (Ch22q11.2D) have an increased prevalence of atopic and autoimmune disease and this has been without explanation. We hypothesized that the increase in atopy was due to homeostatic proliferation of T cells leading to a Th2 skew. We performed intracellular cytokine staining to define Th1/Th2 phenotypes in toddlers (early homeostatic proliferation) and adults (post homeostatic proliferation) with this syndrome. To attempt to understand the predisposition to autoimmunity we performed immunophenotyping analyses to define Th17 cells and B cell subsets. Adult Ch22q11.2D patients had a higher percentage of IL-4+CD4+ T cells than controls. Th17 cells were no different in patients and controls. In addition, adult Ch22q11.2D syndrome patients had significantly lower switched memory B cells, suggesting a dysregulated B cell compartment. These studies demonstrate that the decrement in T cell production has secondary consequences in the immune system, which could mold the patients’ clinical picture. PMID:20472505

  19. The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders

    PubMed Central

    Drew, Liam J.; Crabtree, Gregg W.; Markx, Sander; Stark, Kimberly L.; Chaverneff, Florence; Xu, Bin; Mukai, Jun; Fenelon, Karine; Hsu, Pei-Ken; Gogos, Joseph A.; Karayiorgou, Maria

    2010-01-01

    Over the last fifteen years it has become established that 22q11.2 deletion syndrome (22q11DS) is a true genetic risk factor for schizophrenia. Carriers of deletions in chromosome 22q11.2 develop schizophrenia at rate of 25–30% and such deletions account for as many as 1–2% of cases of sporadic schizophrenia in the general population. Access to a relatively homogeneous population of individuals that suffer from schizophrenia as the result of a shared etiological factor and the potential to generate etiologically valid mouse models provides an immense opportunity to better understand the pathobiology of this disease. In this review we survey the clinical literature associated with the 22q11.2 microdeletions with a focus on neuroanatomical changes. Then, we highlight results from work modeling this structural mutation in animals. The key biological pathways disrupted by the mutation are discussed and how these changes impact the structure and function of neural circuits is described. PMID:20920576

  20. Confirmation that the conotruncal anomaly face syndrome is associated with a deletion within 22q11.2

    SciTech Connect

    Matsuoka, Rumiko; Takao, Atsuyoshi; Kimura, Misa; Kondo, Chisato; Ando, Masahiko; Momma, Kazuo; Imamura, Shin-ichiro; Joh-o, Kunitaka; Ikeda, Kazuo; Nishibatake, Makoto

    1994-11-15

    The so-called {open_quotes}conotruncal anomaly face syndrome{close_quotes} (CTAFS) is characterized by a peculiar facial appearance associated with congenital heart disease (CHD), especially cardiac outflow tract defects such as tetralogy of Fallot (TOF), double outlet ring ventricle (DORV), and truncus arteriosus (TAC). CTAFS and the DiGeorge anomaly (DGA) have many similar phenotypic characteristics, suggesting that they share a common cause. In many cases DGA is known to be associated with monosomy for a region of chromosome 22q11.2. Fifty CTAFS patients and 10 DGA patients, 11 parents couples and 10 mothers of CTAFS patients, and 3 parents couples and 2 mothers of DGA patients were examined by fluorescent in situ hybridization (FISH) using the N25 (D22S75) DGCR probe (Oncor). Monosomy for a region of 22q11.2 was found in 42 CTAFS, 9 DGA, 4 mothers, and 1 father who had CTAF without CHD. The remaining 8 CTAFS patients, 1 DGA patient and 1 mother who had questionable CTAF without CHD, showed no such chromosome abnormality. For the control, 60 patients who had CHD without CTAF or other know malformation syndromes were examined and had no deletion of 22q11.2. Therefore, we conclude that CTAFS is a part of the CATCH 22 syndrome; cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia (CATCH) resulting from 22q11.2 deletions. 20 refs., 3 figs., 2 tabs.

  1. The neurocognitive phenotype of the 22q11.2 deletion syndrome: selective deficit in visual-spatial memory.

    PubMed

    Bearden, C E; Woodin, M F; Wang, P P; Moss, E; McDonald-McGinn, D; Zackai, E; Emannuel, B; Cannon, T D

    2001-08-01

    The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is associated with a high frequency of learning disabilities. Although previous work has demonstrated that verbal skills are typically better preserved than non-verbal skills on both IQ and academic achievement testing in children with this syndrome, such measures are not sufficiently specific to determine a selective cognitive deficit. As part of an ongoing prospective study of patients with this syndrome, 29 children aged 5-17 with confirmed 22q11.2 deletions were assessed with a comprehensive neuropsychological test battery, including matched tasks of verbal and visuospatial memory. Results indicate that 22q patients displayed a selective deficit in visual-spatial memory, which was mirrored by deficits in arithmetic and general visual-spatial cognition. Further, a dissociation between visual-spatial and object memory was observed, indicating further selectivity of this pattern of deficit, and providing evidence for the dissociability of these components of visual cognition. These results indicate that children with 22q11.2 deletions display a specific neurocognitive phenotype, and suggest that this region of Chromosome 22q11 may harbor a gene or genes relevant to the etiology of nonverbal learning deficits. PMID:11780945

  2. Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment

    PubMed Central

    DeBoer, Tracy; Wu, Zhongle; Lee, Aaron; Simon, Tony J

    2007-01-01

    Background Previous investigations of individuals with chromosome 22q11.2 deletion syndrome (DS22q11.2) have reported alterations in both brain anatomy and cognitive function. Neuroanatomical studies have reported multiple abnormalities including changes in both gray and white matter in the temporal lobe, including the amygdala and hippocampus. Separate investigations of cognitive abilities have established the prevalence of general intellectual impairment, although the actual extent to which a single individual is affected varies greatly within the population. The present study was designed to examine structures within the temporal lobe and assess their functional significance in terms of cognition in children with DS22q11.2. Method A total of 72 children (ages 7–14 years) participated in the investigation: 36 children (19 female, 17 male) tested FISH positive for chromosome 22q11.2 deletion (Mean age = 10 years 9 months, ± 2 yr 4 mo) and 36 were age-matched typically developing controls (13 female, 23 male; Mean age = 10 years 6 months, ± 1 yr 11 mo). For each subject, a three-dimensional high-resolution (1 mm isotropic) T1-weighted structural MRI was acquired. Neuroanatomical guidelines were used to define borders of the amygdala and hippocampus bilaterally and volumes were calculated based on manual tracings of the regions. The Wechsler Intelligence Scale for Children (WISC) was also administered. Results Volumetric reductions in total gray matter, white matter, and both the amygdala and hippocampus bilaterally were observed in children with DS22q11.2. Reductions in the left hippocampus were disproportionate to decreases in gray matter after statistically controlling for group differences in total gray matter, age, and data collection site. This specific reduction in hippocampal volume was significantly correlated with performance on standardized measures of intelligence, whereas the other neuroanatomical measures were not (gray/white matter, CSF, and

  3. Increased Levels of Interferon-Inducible Protein 10 (IP-10) in 22q11.2 Deletion Syndrome.

    PubMed

    Aresvik, D M; Lima, K; Øverland, T; Mollnes, T E; Abrahamsen, T G

    2016-03-01

    The 22q11.2 deletion syndrome (22q11.2 DS), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:4000 births. These patients may suffer from affection of many organ systems with cardiac malformations, thymic hypoplasia or aplasia, hypoparathyroidism, palate anomalies and psychiatric disorders being the most frequent. The incidence of autoimmune diseases is increased in older patients. The aim of the present study was to examine a cytokine profile in patients with 22q11.2 DS by measuring a broad spectrum of serum cytokines. Patients with a proven deletion of chromosome 22q11.2 (n = 55) and healthy individuals (n = 54) recruited from an age- and sex-comparable group were included in the study. Serum levels of 27 cytokines, including chemokines and growth factors, were analysed using multiplex technology. Interferon-inducible protein 10 (IP-10) was also measured by ELISA to confirm the multiplex results. The 22q11.2 DS patients had distinctly and significantly raised levels of pro-inflammatory and angiostatic chemokine IP-10 (P < 0.001) compared to controls. The patients with congenital heart defects (n = 31) had significantly (P = 0.018) raised serum levels of IP-10 compared to patients born without heart defects (n = 24). The other cytokines investigated were either not detectable or did not differ between patients and controls. PMID:26708691

  4. Decreased DGCR8 Expression and miRNA Dysregulation in Individuals with 22q11.2 Deletion Syndrome

    PubMed Central

    Sellier, Chantal; Hwang, Vicki J.; Dandekar, Ravi; Durbin-Johnson, Blythe; Charlet-Berguerand, Nicolas; Ander, Bradley P.; Sharp, Frank R.; Angkustsiri, Kathleen; Simon, Tony J.; Tassone, Flora

    2014-01-01

    Deletion of the 1.5–3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%), conotruncal defects of the heart (CHD; 70–80%), hypocalcemia (20–60%), and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS. PMID:25084529

  5. Facial emotion perception by intensity in children and adolescents with 22q11.2 deletion syndrome.

    PubMed

    Leleu, Arnaud; Saucourt, Guillaume; Rigard, Caroline; Chesnoy, Gabrielle; Baudouin, Jean-Yves; Rossi, Massimiliano; Edery, Patrick; Franck, Nicolas; Demily, Caroline

    2016-03-01

    Difficulties in the recognition of emotions in expressive faces have been reported in people with 22q11.2 deletion syndrome (22q11.2DS). However, while low-intensity expressive faces are frequent in everyday life, nothing is known about their ability to perceive facial emotions depending on the intensity of expression. Through a visual matching task, children and adolescents with 22q11.2DS as well as gender- and age-matched healthy participants were asked to categorise the emotion of a target face among six possible expressions. Static pictures of morphs between neutrality and expressions were used to parametrically manipulate the intensity of the target face. In comparison to healthy controls, results showed higher perception thresholds (i.e. a more intense expression is needed to perceive the emotion) and lower accuracy for the most expressive faces indicating reduced categorisation abilities in the 22q11.2DS group. The number of intrusions (i.e. each time an emotion is perceived as another one) and a more gradual perception performance indicated smooth boundaries between emotional categories. Correlational analyses with neuropsychological and clinical measures suggested that reduced visual skills may be associated with impaired categorisation of facial emotions. Overall, the present study indicates greater difficulties for children and adolescents with 22q11.2DS to perceive an emotion in low-intensity expressive faces. This disability is subtended by emotional categories that are not sharply organised. It also suggests that these difficulties may be associated with impaired visual cognition, a hallmark of the cognitive deficits observed in the syndrome. These data yield promising tracks for future experimental and clinical investigations. PMID:26149605

  6. Social cognition in 22q11.2 microdeletion syndrome: relevance to psychosis?

    PubMed

    Jalbrzikowski, Maria; Carter, Chelsea; Senturk, Damla; Chow, Carolyn; Hopkins, Jessica M; Green, Michael F; Galván, Adriana; Cannon, Tyrone D; Bearden, Carrie E

    2012-12-01

    22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis. PMID:23122739

  7. Social cognition in 22q11.2 microdeletion syndrome: relevance to psychosis?

    PubMed

    Jalbrzikowski, Maria; Carter, Chelsea; Senturk, Damla; Chow, Carolyn; Hopkins, Jessica M; Green, Michael F; Galván, Adriana; Cannon, Tyrone D; Bearden, Carrie E

    2012-12-01

    22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis.

  8. [NEGATIVE IMPACT OF CHROMOSOME 22Q11 MICRODELETION ON RESULTS OF TREATMENT IN PATIENTS, SUFFERING CONONTRUNCAL FAILURES OF HEART AND MAIN AORTO-PULMONARY COLLATERAL ARTERIES].

    PubMed

    Bablyak, O D; Yalynska, T A; Skorokhod, I M

    2015-05-01

    Dependence of results of surgical treatment in 42 patients, suffering conotruncal failures and main aorto-pulmonary collateral arteries from presence of the chromosome 22q11 deletion syndrome, was analyzed. While presence of the chromosome 22q11 deletion syndrome duration of treatment of patients in intensive therapy unit and artificial pulmonary ventilation are longer, pressure in a pulmonary artery system after radical operative failures correction is higher, general lethality is bigger, than while the chromosome 22q11 deletion syndrome absence. The data obtained must be taken into account while determining tactics of treatment in patients with confirmed diagnosis of the chromosome 22q11 deletion syndrome.

  9. Ranbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation

    PubMed Central

    Paronett, Elizabeth M.; Meechan, Daniel W.; Karpinski, Beverly A.; LaMantia, Anthony-Samuel; Maynard, Thomas M.

    2015-01-01

    Ranbp1, a Ran GTPase-binding protein implicated in nuclear/cytoplasmic trafficking, is included within the DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS) critical region associated with behavioral impairments including autism and schizophrenia. Ranbp1 is highly expressed in the developing forebrain ventricular/subventricular zone but has no known obligate function during brain development. We assessed the role of Ranbp1 in a targeted mouse mutant. Ranbp1−/− mice are not recovered live at birth, and over 60% of Ranbp1−/− embryos are exencephalic. Non-exencephalic Ranbp1−/− embryos are microcephalic, and proliferation of cortical progenitors is altered. At E10.5, radial progenitors divide more slowly in the Ranpb1−/− dorsal pallium. At E14.5, basal, but not apical/radial glial progenitors, are compromised in the cortex. In both E10.5 apical and E14.5 basal progenitors, M phase of the cell cycle appears selectively retarded by loss of Ranpb1 function. Ranbp1−/−-dependent proliferative deficits substantially diminish the frequency of layer 2/3, but not layer 5/6 cortical projection neurons. Ranbp1−/− cortical phenotypes parallel less severe alterations in LgDel mice that carry a deletion parallel to many (but not all) 22q11.2 DS patients. Thus, Ranbp1 emerges as a microcephaly gene within the 22q11.2 deleted region that may contribute to altered cortical precursor proliferation and neurogenesis associated with broader 22q11.2 deletion. PMID:25452572

  10. 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

    PubMed Central

    Mariano, Margaret A.; Tang, Kerri; Kurtz, Matthew; Kates, Wendy R.

    2015-01-01

    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 8 month 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 7.96 months. 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. PMID:26044111

  11. Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

    PubMed Central

    Lindgren, Valerie; McRae, Anne; Dineen, Richard; Saulsberry, Alexandria; Hoganson, George; Schrift, Michael

    2015-01-01

    We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D–E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype–phenotype correlations which are still being generated for these chromosomal anomalies. PMID:26247050

  12. 3 generation pedigree with paternal transmission of the 22q11.2 deletion syndrome: Intrafamilial phenotypic variability.

    PubMed

    Vergaelen, Elfi; Swillen, Ann; Van Esch, Hilde; Claes, Stephan; Van Goethem, Gert; Devriendt, Koenraad

    2015-04-01

    In this case report, we present a paternal transmission of a classic 3 Mb 22q11.2 deletion syndrome (22q11.2 DS) in a 3 generation family. In this family a young girl, her father, her uncle and her grandfather were diagnosed with this disorder. All carriers showed phenotypic expression, there were no unaffected siblings in the second or third generation. Presenting symptoms in the patient in first generation (grandfather) were psoriatic arthritis, thrombocytopenia and a right aortic arch. There was no intellectual disability. The second generation uncle was known with a severe intellectual disability, mild facial characteristics, a septal defect and a clubfoot, whereas the second generation father had a tetralogy of Fallot, no intellectual disability and minimal facial characteristics. The third generation daughter had a moderate intellectual disability, hypernasal speech, triphalangeal thumb, severe speech and language development delay, pronounced facial characteristics and a diagnosis of ADHD. It was notable that the expression in the two brothers of the second generation gives two very different clinical phenotypes with a severe intellectual disability in the oldest brother. This report describes a pronounced clinical variability in a 3 generation familial 22q11.2 deletion with paternal transmission. We can assume that several mechanisms play an important role in the heterogeneity and part of the answer should be found in the genetic background underlying the 22q11.2 deletion. In addition in this family the neuropsychiatric phenotype and intellectual disability seem to be associated with a lower level of social and occupational functioning while a congenital heart disease does not. This clinical report illustrates that a detailed description of these patients can be very informative and still increase the knowledge on this heterogeneous syndrome. For the clinicians working with these patients it emphasizes the need for a multidisciplinary approach that takes

  13. Obstructive Sleep Apnea Syndrome in Children with 22q11.2 Deletion Syndrome after Operative Intervention for Velopharyngeal Insufficiency

    PubMed Central

    Crockett, David Jeffrey; Goudy, Steven L.; Chinnadurai, Sivakumar; Wootten, Christopher Todd

    2014-01-01

    Introduction: Surgical treatment of velopharyngeal insufficiency (VPI) in 22q11.2 deletion syndrome is often warranted. In this patient population, VPI is characterized by poor palatal elevation and muscular hypotonia with an intact palate. We hypothesize that 22q11.2 deletion patients are at greater risk of obstructive sleep apnea (OSA) after surgical correction of VPI, due, in part, to their functional hypotonia, large velopharyngeal gap size, and the need to surgically obstruct the velopharynx. Methods: We performed a retrospective analysis of patients with 22q11.2 deletion syndrome treated at a tertiary pediatric hospital between the years of 2002 and 2012. The incidence of VPI, need for surgery, post-operative polysomnogram, post-operative VPI assessment, and OSA treatments were evaluated. Results: Forty-three patients (18 males, 25 females, ages 1–14 years) fitting the inclusion criteria were identified. Twenty-eight patients were evaluated by speech pathology due to hypernasality. Twenty-one patients had insufficient velopharyngeal function and required surgery. Fifteen underwent pharyngeal flap surgery, three underwent sphincter pharyngoplasty, two underwent Furlow palatoplasty, and one underwent combined sphincter pharyngoplasty with Furlow palatoplasty. Of these, eight had post-operative snoring. Six of these underwent polysomnography (five underwent pharyngeal flap surgeries and one underwent sphincter pharyngoplasty). Four patients were found to have OSA based on the results of the polysomnography (average apnea/hypopnea index of 4.9 events/h, median = 5.1, SD = 2.1). Two required continuous positive airway pressure (CPAP) due to moderate OSA. Conclusion: Surgery is often necessary to correct VPI in patients with 22q11.2 deletion syndrome. Monitoring for OSA should be considered after surgical correction of VPI due to a high occurrence in this population. Furthermore, families should be counseled of the risk of OSA after surgery and the

  14. A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review

    PubMed Central

    Fernández, Luis; Nevado, Julián; Santos, Fernando; Heine-Suñer, Damià; Martinez-Glez, Victor; García-Miñaur, Sixto; Palomo, Rebeca; Delicado, Alicia; Pajares, Isidora López; Palomares, María; García-Guereta, Luis; Valverde, Eva; Hawkins, Federico; Lapunzina, Pablo

    2009-01-01

    Background Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. Methods We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Results Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. Conclusion The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors. PMID

  15. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    SciTech Connect

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L.

    1994-09-01

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

  16. Social Cognition Dysfunction in Adolescents with 22q11.2 Deletion Syndrome (Velo-Cardio-Facial Syndrome): Relationship with Executive Functioning and Social Competence/Functioning

    ERIC Educational Resources Information Center

    Campbell, L. E.; McCabe, K. L.; Melville, J. L.; Strutt, P. A.; Schall, U.

    2015-01-01

    Background: Social difficulties are often noted among people with intellectual disabilities. Children and adults with 22q.11.2 deletion syndrome (22q11DS) often have poorer social competence as well as poorer performance on measures of executive and social-cognitive skills compared with typically developing young people. However, the relationship…

  17. Intellectual Functioning in Relation to Autism and ADHD Symptomatology in Children and Adolescents with 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Hidding, E.; Swaab, H.; Sonneville, L. M. J.; Engeland, H.; Sijmens-Morcus, M. E. J.; Klaassen, P. W. J.; Duijff, S. N.; Vorstman, J. A. S.

    2015-01-01

    Background: The 22q11.2 deletion syndrome (22q11DS; velo-cardio-facial syndrome) is associated with an increased risk of various disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). With this study, we aimed to investigate the relation between intellectual functioning and severity of ASD and ADHD…

  18. Social Cognitive Training in Adolescents with Chromosome 22q11.2 Deletion Syndrome: Feasibility and Preliminary Effects of the Intervention

    ERIC Educational Resources Information Center

    Shashi, V.; Harrell, W.; Eack, S.; Sanders, C.; McConkie-Rosell, A.; Keshavan, M. S.; Bonner, M. J.; Schoch, K.; Hooper, S. R.

    2015-01-01

    Background: Children with chromosome 22q11.2 deletion syndrome (22q11DS) often have deficits in social cognition and social skills that contribute to poor adaptive functioning. These deficits may be of relevance to the later occurrence of serious psychiatric illnesses such as schizophrenia. Yet, there are no evidence-based interventions to improve…

  19. Comparing the neural bases of self-referential processing in typically developing and 22q11.2 adolescents.

    PubMed

    Schneider, Maude; Debbané, Martin; Lagioia, Annalaura; Salomon, Roy; d'Argembeau, Arnaud; Eliez, Stephan

    2012-04-01

    The investigation of self-reflective processing during adolescence is relevant, as this period is characterized by deep reorganization of the self-concept. It may be the case that an atypical development of brain regions underlying self-reflective processing increases the risk for psychological disorders and impaired social functioning. In this study, we investigated the neural bases of self- and other-related processing in typically developing adolescents and youths with 22q11.2 deletion syndrome (22q11DS), a rare neurogenetic condition associated with difficulties in social interactions and increased risk for schizophrenia. The fMRI paradigm consisted in judging if a series of adjectives applied to the participant himself/herself (self), to his/her best friend or to a fictional character (Harry Potter). In control adolescents, we observed that self- and other-related processing elicited strong activation in cortical midline structures (CMS) when contrasted with a semantic baseline condition. 22q11DS exhibited hypoactivation in the CMS and the striatum during the processing of self-related information when compared to the control group. Finally, the hypoactivation in the anterior cingulate cortex was associated with the severity of prodromal positive symptoms of schizophrenia. The findings are discussed in a developmental framework and in light of their implication for the development of schizophrenia in this at-risk population.

  20. The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

    PubMed Central

    Leite, Ana Julia Cunha; Pinto, Irene Plaza; Cunha, Damiana Mirian da Cruz e; Ribeiro, Cristiano Luiz; da Silva, Claudio Carlos; da Cruz, Aparecido Divino; Minasi, Lysa Bernardes

    2016-01-01

    The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications. PMID:27123452

  1. Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion

    PubMed Central

    Drew, Liam J; Stark, Kimberly L; Fénelon, Karine; Karayiorgou, Maria; MacDermott, Amy B; Gogos, Joseph A

    2011-01-01

    22q11.2 chromosomal deletions are recurrent copy number mutations that increase the risk of schizophrenia around thirty-fold. Deletion of the orthologous chromosomal region in mice offers an opportunity to characterize changes to neuronal structure and function that may account for the development of this disease. The hippocampus has been implicated in schizophrenia pathogenesis, is reduced in volume in 22q11.2 deletion carriers and displays altered neuronal structure in a mouse model of the mutation (Df(16)A+/− mice). Here we investigate hippocampal CA1 physiology, hippocampal-dependent spatial memory and novelty-induced hippocampal activation in Df(16) A+/− mice. We found normal spatial reference memory (as assayed by the Morris water maze test) as well as modest but potentially important deficits in physiology. In particular, a reduction in the level of inhibition of CA1 pyramidal neurons was observed, implying a decrease in interneuron activity. Additionally, deficits in LTP were observed using certain induction protocols. Induction of c-Fos expression by exploration of a novel environment suggested a relative sparing of CA1 and dentate gyrus function but showed a robust decrease in the number of activated CA3 pyramidal neurons in Df(16) A+/− mice. Overall, experiments performed in this 22q11.2 deletion model demonstrated deficits of various degrees across different regions of the hippocampus, which together may contribute to the increased risk of developing schizophrenia. PMID:21635953

  2. Comparing the neural bases of self-referential processing in typically developing and 22q11.2 adolescents.

    PubMed

    Schneider, Maude; Debbané, Martin; Lagioia, Annalaura; Salomon, Roy; d'Argembeau, Arnaud; Eliez, Stephan

    2012-04-01

    The investigation of self-reflective processing during adolescence is relevant, as this period is characterized by deep reorganization of the self-concept. It may be the case that an atypical development of brain regions underlying self-reflective processing increases the risk for psychological disorders and impaired social functioning. In this study, we investigated the neural bases of self- and other-related processing in typically developing adolescents and youths with 22q11.2 deletion syndrome (22q11DS), a rare neurogenetic condition associated with difficulties in social interactions and increased risk for schizophrenia. The fMRI paradigm consisted in judging if a series of adjectives applied to the participant himself/herself (self), to his/her best friend or to a fictional character (Harry Potter). In control adolescents, we observed that self- and other-related processing elicited strong activation in cortical midline structures (CMS) when contrasted with a semantic baseline condition. 22q11DS exhibited hypoactivation in the CMS and the striatum during the processing of self-related information when compared to the control group. Finally, the hypoactivation in the anterior cingulate cortex was associated with the severity of prodromal positive symptoms of schizophrenia. The findings are discussed in a developmental framework and in light of their implication for the development of schizophrenia in this at-risk population. PMID:22483077

  3. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  4. Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.

    PubMed

    Herman, Sean B; Guo, Tingwei; McGinn, Donna M McDonald; Blonska, Anna; Shanske, Alan L; Bassett, Anne S; Chow, Eva W C; Bowser, Mark; Sheridan, Molly; Beemer, Frits; Devriendt, Koen; Swillen, Ann; Breckpot, Jeroen; Digilio, M Cristina; Marino, Bruno; Dallapiccola, Bruno; Carpenter, Courtney; Zheng, Xin; Johnson, Jacob; Chung, Jonathan; Higgins, Anne Marie; Philip, Nicole; Simon, Tony; Coleman, Karlene; Heine-Suner, Damian; Rosell, Jordi; Kates, Wendy; Devoto, Marcella; Zackai, Elaine; Wang, Tao; Shprintzen, Robert; Emanuel, Beverly S; Morrow, Bernice E

    2012-11-01

    Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000-1/4,000 live births. Approximately 9-11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, we hypothesized that DNA variants in the remaining allele of TBX1 may confer risk to CP in patients with 22q11DS. To test the hypothesis, we evaluated TBX1 exon sequencing (n = 360) and genotyping data (n = 737) with respect to presence (n = 54) or absence (n = 683) of CP in patients with 22q11DS. Two upstream SNPs (rs4819835 and rs5748410) showed individual evidence for association but they were not significant after correction for multiple testing. Associations were not identified between DNA variants and haplotypes in 22q11DS patients with CP. Overall, this study indicates that common DNA variants in TBX1 may be nominally causative for CP in patients with 22q11DS. This raises the possibility that genes elsewhere on the remaining allele of 22q11.2 or in the genome could be relevant.

  5. The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

    PubMed Central

    Scott, Julia A.; Goodrich-Hunsaker, Naomi; Kalish, Kristopher; Lee, Aaron; Hunsaker, Michael R.; Schumann, Cynthia M.; Carmichael, Owen T.; Simon, Tony J.

    2016-01-01

    Background Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. Methods We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. Results We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. Limitations Shape alterations are not specific to hippocampal subfields. Conclusion Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection

  6. Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study

    PubMed Central

    Repetto, Gabriela M; Guzmán, M Luisa; Delgado, Iris; Loyola, Hugo; Palomares, Mirta; Lay-Son, Guillermo; Vial, Cecilia; Benavides, Felipe; Espinoza, Karena; Alvarez, Patricia

    2014-01-01

    Objective Chromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients. Design Demographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death. Setting Genetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion. Outcomes Fatality rate and associated factors. Results 59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects. Conclusions In this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival

  7. Association of the family environment with behavioural and cognitive outcomes in children with chromosome 22q11.2 deletion syndrome

    PubMed Central

    Allen, T. M.; Hersh, J.; Schoch, K.; Curtiss, K.; Hooper, S. R.; Shashi, V.

    2014-01-01

    Background Children with 22q11.2 deletion syndrome (22q11DS) are at risk for social-behavioural and neurocognitive sequelae throughout development. The current study examined the impact of family environmental characteristics on social-behavioural and cognitive outcomes in this pediatric population. Method Guardians of children with 22q11DS were recruited through two medical genetics clinics. Con senting guardians were asked to complete several questionnaires regarding their child's social, emotional and behavioural functioning, as well as family social environment and parenting styles. Children with 22q11DS were asked to undergo a cognitive assessment, including IQ and achievement testing, and measures of attention, executive function and memory. Results Modest associations were found between aspects of the family social environment and parenting styles with social-behavioural and cognitive/academic outcomes. Regression models indicated that physical punishment, socioeconomic status, parental control and family organisation significantly predicted social-behavioural and cognitive outcomes in children with 22q11DS. Conclusion Characteristics of the family social environment and parenting approaches appear to be associated with functional outcomes of children with 22q11DS. Understanding the impact of environmental variables on developmental outcomes can be useful in determining more effective targets for intervention. This will be important in order to improve the quality of life of individuals affected by 22q11DS. PMID:23742203

  8. Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

    PubMed

    Prodhan, P; Gossett, J M; Rycus, P T; Gupta, P

    2015-11-01

    The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children <18 years undergoing heart surgery for either common atrio-ventricular canal, tetralogy of Fallot, truncus arteriosus or transposition of the great vessels and interrupted aortic arch and requiring ECMO, from 1998-2011. The outcomes evaluated included mortality, ECMO duration and length of hospital stay in patients with del22q11 syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls.

  9. Extracorporeal membrane oxygenation in children with heart disease and del22q11 syndrome: a review of the Extracorporeal Life Support Organization Registry.

    PubMed

    Prodhan, P; Gossett, J M; Rycus, P T; Gupta, P

    2015-11-01

    The study objective was to evaluate outcomes among children with del22q11 (DiGeorge) syndrome supported on ECMO for heart disease. The ELSO registry database was queried to include all children <18 years undergoing heart surgery for either common atrio-ventricular canal, tetralogy of Fallot, truncus arteriosus or transposition of the great vessels and interrupted aortic arch and requiring ECMO, from 1998-2011. The outcomes evaluated included mortality, ECMO duration and length of hospital stay in patients with del22q11 syndrome and with no del22q11 syndrome. Eighty-eight ECMO runs occurred in children with del22q11 syndrome while 2694 ECMO runs occurred in children without del22q11 syndrome. For patients with heart defects receiving ECMO, del22q11 syndrome did not confer a significant mortality risk or an increased risk of infectious complications before or while on ECMO support. Neither the duration of ECMO nor mechanical ventilation prior to ECMO deployment were prolonged in patients with del22q11 syndrome compared to the controls. PMID:25795680

  10. Idiopathic thromobocytopenic purpura in two mothers of children with DiGeorge sequence: A new component manifestation of deletion 22q11?

    SciTech Connect

    Levy, A.; Philip, N.; Michel, G.

    1997-04-14

    The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS. 12 refs., 4 figs., 1 tab.

  11. A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH.

    PubMed

    Poirsier, Céline; Besseau-Ayasse, Justine; Schluth-Bolard, Caroline; Toutain, Jérôme; Missirian, Chantal; Le Caignec, Cédric; Bazin, Anne; de Blois, Marie Christine; Kuentz, Paul; Catty, Marie; Choiset, Agnès; Plessis, Ghislaine; Basinko, Audrey; Letard, Pascaline; Flori, Elisabeth; Jimenez, Mélanie; Valduga, Mylène; Landais, Emilie; Lallaoui, Hakima; Cartault, François; Lespinasse, James; Martin-Coignard, Dominique; Callier, Patrick; Pebrel-Richard, Céline; Portnoi, Marie-France; Busa, Tiffany; Receveur, Aline; Amblard, Florence; Yardin, Catherine; Harbuz, Radu; Prieur, Fabienne; Le Meur, Nathalie; Pipiras, Eva; Kleinfinger, Pascale; Vialard, François; Doco-Fenzy, Martine

    2016-06-01

    Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.

  12. Partial trisomy 22 (q11.2-q13.1) as a result of duplication and pericentric inversion.

    PubMed Central

    Prasher, V P; Roberts, E; Norman, A; Butler, A C; Krishnan, V H; McMullan, D J

    1995-01-01

    A case of a 27 year old male with a duplication of part of the long arm of chromosome 22 (22q11.2-q13.1) together with a pericentric inversion of the same chromosome is reported. Particular phenotypic features of note include absence of speech, persistent self-injury, lack of daily living skills, colobomata, and very poor vision. Similarities between this case and other case reports of duplications of the long arm of chromosome 22 are discussed. Images PMID:7643363

  13. [Catch-22? Wide variety of phenotypes associated with the chromosome 22q11 deletion syndrome in two patients].

    PubMed

    Till, Ágnes; Hadzsiev, Kinga; Lőcsei-Fekete, Anett; Czakó, Márta; Duga, Balázs; Melegh, Béla

    2015-11-01

    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.

  14. Microduplication 22q11.2: a description of the clinical, developmental and behavioral characteristics during childhood.

    PubMed

    Van Campenhout, S; Devriendt, K; Breckpot, J; Frijns, J-P; Peeters, H; Van Buggenhout, G; Van Esch, H; Maes, B; Swillen, A

    2012-01-01

    Microduplication 22q11.2 is a recently discovered genomic disorder. So far, targeted research on the cognitive and behavioral characteristics of individuals with this microduplication is limited. Therefore, 11 Flemish children (3-13 years old) with a microduplication 22q 1.2 were investigated in order to describe their clinical, developmental and behavioral characteristics. We measured their general intelligence, visual-motor capacities, attention, behavioral problems and characteristics of autism. In addition, there was an interview with the parents on developmental history and we reviewed available information from other specialists. The results show that the cognitive and behavioral phenotype of the children with microduplication 22q.11.2 is very wide and heterogeneous. Some of the children have a cognitively nearly normal development whereas others are more severely affected. All children had some degree of developmental delay and some of them have an intellectual disability. The most common clinical features include congenital malformations such as heart defects and cleft lip, feeding problems, hearing impairment and facial dysmorphism. The most common non-medical problems are learning difficulties, motor impairment, attention deficits, social problems and behavioral problems. There is no correlation between the size of the duplication and the phenotype. PMID:22876571

  15. Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder

    PubMed Central

    Jalbrzikowski, Maria; Lazaro, Maria T.; Gao, Fuying; Huang, Alden; Chow, Carolyn; Geschwind, Daniel H.

    2015-01-01

    Background 22q11.2 Deletion Syndrome (22q11DS) represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD) in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes. Methods We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential expression (DE) and networks of co-expressed genes related to phenotypic variation within 22q11DS patients. Whole-genome transcriptional profiling was performed using Illumina Human HT-12 microarrays. Data mining techniques were used to validate our results against independent samples of both peripheral blood and brain tissue from idiopathic psychosis and ASD cases. Results Eighty-five percent of 22q11DS individuals (N = 39) carried the typical 3 Mb deletion, with significant variability in deletion characteristics in the remainder of the sample (N = 7). DE analysis and weighted gene co-expression network analysis (WGCNA) identified expression changes related to psychotic symptoms in patients, including a module of co-expressed genes which was associated with psychosis in 22q11DS and involved in pathways associated with transcriptional regulation. This module was enriched for brain-expressed genes, was not related to antipsychotic medication use, and significantly overlapped with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE and WGCNA analyses implicated dysregulation of immune response pathways. The ASD-associated module showed significant overlap with genes previously associated with idiopathic ASD. Conclusion These findings further support the use of peripheral tissue in the study of major mutational models of diseases affecting the brain, and point towards specific pathways dysregulated in 22q11DS carriers with psychosis and ASD. PMID:26201030

  16. Brain and Behavior in Children with 22Q11.2 Deletion Syndrome: A Volumetric and Voxel-Based Morphometry MRI Study

    ERIC Educational Resources Information Center

    Campbell, Linda E.; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Catani, Marco; Ng, Virginia; Van Amelsvoort, Therese; Chitnis, Xavier; Cutter, William; Murphy, Declan G. M.; Murphy, Kieran C.

    2006-01-01

    In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit hyperactivity disorder…

  17. Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

    PubMed Central

    Uddin, Raihan K; Zhang, Yang; Siu, Victoria Mok; Fan, Yao-Shan; O'Reilly, Richard L; Rao, Jay; Singh, Shiva M

    2006-01-01

    Background Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. Methods Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. Results This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. Conclusion This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion. PMID:16512914

  18. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia

    PubMed Central

    Liu, Hui; Heath, Simon C.; Sobin, Christina; Roos, J. Louw; Galke, Brandi L.; Blundell, Maude L.; Lenane, Marge; Robertson, Brian; Wijsman, Ellen M.; Rapoport, Judith L.; Gogos, Joseph A.; Karayiorgou, Maria

    2002-01-01

    The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that ≈20–30% of individuals with 22q11 microdeletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood. Analysis of the extent of these microdeletions by using polymorphic markers afforded further refinement of this locus to a region of ≈1.5 Mb. Recently, a high rate of 22q11 microdeletions was also reported for a cohort of 47 patients with Childhood Onset Schizophrenia, a rare and severe form of schizophrenia with onset by age 13. It is therefore likely that this 1.5-Mb region contains one or more genes that predispose to schizophrenia. In three independent samples, we provide evidence for a contribution of the PRODH2/DGCR6 locus in 22q11-associated schizophrenia. We also uncover an unusual pattern of PRODH2 gene variation that mimics the sequence of a linked pseudogene. Several of the pseudogene-like variants we identified result in missense changes at conserved residues and may prevent synthesis of a fully functional enzyme. Our results have implications for understanding the genetic basis of the 22q11-associated psychiatric phenotypes and provide further insights into the genomic instability of this region. PMID:11891283

  19. Is theory of mind related to social dysfunction and emotional problems in 22q11.2 deletion syndrome (velo-cardio-facial syndrome)?

    PubMed

    Campbell, Linda E; Stevens, Angela F; McCabe, Kathryn; Cruickshank, Lynne; Morris, Robin G; Murphy, Declan G M; Murphy, Kieran C

    2011-06-01

    Social dysfunction is intrinsically involved in severe psychiatric disorders such as depression and psychosis and linked with poor theory of mind. Children with 22q11.2 deletion syndrome (22q11DS, or velo-cardio-facial syndrome) have poor social competence and are also at a particularly high risk of developing mood (40%) and psychotic (up to 30%) disorders in adolescence and young adulthood. However, it is unknown if these problems are associated with theory of mind skills, including underlying social-cognitive and social-perceptual mechanisms. The present cross-sectional study included classic social-cognitive false-belief and mentalising tasks and social-perceptual face processing tasks. The performance of 50 children with 22q11DS was compared with 31 age-matched typically developing sibling controls. Key findings indicated that, while younger children with 22q11DS showed impaired acquisition of social-cognitive skills, older children with 22q11DS were not significantly impaired compared with sibling controls. However, children with 22q11DS were found to have social-perceptual deficits, as demonstrated by difficulties in matching faces on the basis of identity, emotion, facial speech and gaze compared with sibling controls. Furthermore, performance on the tasks was associated with age, language ability and parentally rated social competence and emotional problems. These results are discussed in relation to the importance of a better delineation of social competence in this population.

  20. De novo tandem duplication of chromosome segement 22q11-q12: Clinical, cytogenetic, and molecular characterization

    SciTech Connect

    Lindsay, E.A.; Shaffer, L.G.; Carrozzo, R.

    1995-04-10

    We report on a case of duplication of the segment 22q11-q12 due to a de novo duplication. Molecular cytogenetics studies demonstrated this to be a tandem duplication, flanked proximally by the marker D22Z4, a centromeric alpha satellite DNA repeat, and distally by D22S260, an anonymous DNA marker proximal to the Ewing sarcoma breakpoint. The segment includes the regions responsible for the {open_quotes}cat-eye{close_quotes}, Di George, and velo-cardio-facial syndromes and extends distal to the breakpoint cluster region (BCR). The clinical picture is dominated by the cardiac defects and includes findings reminiscent of {open_quotes}cat-eye{close_quotes} syndrome. These findings reinforce the hypothesis that the proximal 22q region contains dosage-sensitive genes involved in development. 20 refs., 3 figs.

  1. Prevalence of microdeletion 22q11 in patients with hypernasal speech due to velopharyngeal insufficiency: Expanded phenotype and clinical comparison to nondeletion

    SciTech Connect

    Siegel-Bartelt, J.; Cytrynbaum, C.; Witzel, M.A.; Teshima, I.E.

    1994-09-01

    Microdeletion 22q11.2 has been reported as a frequent ethiology of both velocardiofacial (VCF) and DiGeorge syndromes. We have studied the prevalence of microdeletion 22q11 in a group of patients ascertained through a Speech and Language clinic presenting with (1) velopharyngeal insufficiency (VPI) and (2) difficultly in school. Growth parameters were measured, and facies were scored for features of VCF. Microdeletions were detected at locus D22S75 by FISH with probe N25 (Oncor), and at 22q11.2 with high resolution banding analysis (HRB). One child with typical VCF facies was considered to have a deletion at 22q11 with HRB, but is not deleted with N25, indicating that N25 may not detect all deletion patients. An additional 8/30 children tested to date were deleted with the N25 probe. Heart defects were present in only 2/8 deletion patients: VSD/ASD and PS/AS. One N25 deletion patient was atypica; he has a tall, lanky habitus (height = 90%), and facies not characteristic of CVF. As expected, there is a trend to lower head size, smaller ear size, and more typical facies in deletion patients; however, four of the nondeletion patients also had a clinical diagnosis of VCF. Medially displaced carotid arteries were present in both groups, which is therefore not a diagnostic feature of microdeletion 22q11. Our findings indicate that the microdeletion 22q11 is frequent (26% in this series) in a population with VPI, even when not selected for typical facies. We believe this series supports the view that microdeletion 22q11 has a broader clinical phenotype than previously recognized.

  2. Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

    PubMed

    Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

    2014-09-01

    The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. PMID:24853458

  3. Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

    PubMed

    Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

    2014-09-01

    The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.

  4. Common and specific impairments in attention functioning in girls with chromosome 22q11.2 deletion, fragile X or Turner syndromes

    PubMed Central

    2014-01-01

    Background Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention. Methods Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices. Results Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system. Conclusions These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory. PMID:24628892

  5. Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts.

    PubMed

    Yi, James J; Weinberger, Ronnie; Moore, Tyler M; Calkins, Monica E; Guri, Yael; McDonald-McGinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Raquel E; Gothelf, Doron; Gur, Ruben C

    2016-07-01

    Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12-36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations. PMID:27200494

  6. Whole genome sequencing and integrative genomic analysis approach on two 22q11.2 deletion syndrome family trios for genotype to phenotype correlations

    PubMed Central

    Chung, Jonathan H.; Cai, Jinlu; Suskin, Barrie G.; Zhang, Zhengdong; Coleman, Karlene

    2015-01-01

    The 22q11.2 deletion syndrome (22q11DS) affects 1:4000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole genome sequencing and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order to prioritize rare, predicted deleterious, coding and non-coding single nucleotide variants (SNVs) and insertion/deletions (INDELs) from whole genome sequencing (WGS). We sequenced two unrelated probands with 22q11DS, with contrasting clinical findings, and their unaffected parents. Proband P1 had cognitive impairment, psychotic episodes, anxiety, and tetralogy of Fallot (TOF); while proband P2 had juvenile rheumatoid arthritis but no other major clinical findings. In P1, we identified common variants in COMT and PRODH on 22q11.2 as well as rare potentially deleterious DNA variants in other behavioral/neurocognitive genes. We also identified a de novo SNV in ADNP2 (NM_014913.3:c.2243G>C), encoding a neuroprotective protein that may be involved in behavioral disorders. In P2, we identified a novel non-synonymous SNV in ZFPM2 (NM_012082.3:c.1576C>T), a known causative gene for TOF, which may act as a protective variant downstream of TBX1, haploinsufficiency of which is responsible for congenital heart disease in individuals with 22q11DS. PMID:25981510

  7. 8p23.1 Interstitial Deletion in a Patient with Congenital Cardiopathy, Neurobehavioral Disorders, and Minor Signs Suggesting 22q11.2 Deletion Syndrome.

    PubMed

    Molck, Miriam C; Monteiro, Fabíola P; Simioni, Milena; Gil-da-Silva-Lopes, Vera L

    2015-09-01

    Copy number variation studies of known disorders have the potential to improve the characterization of clinical phenotypes and may help identifying candidate genes and their pathways. The authors described a child with congenital heart disease, microcephaly, facial dysmorphisms, developmental delay, learning difficulties, and behavioral problems. There was initially a clinical suspicion of 22q11.2 deletion syndrome (22q11.2 DS), but molecular cytogenetic analysis (array genomic hybridization [aGH]) showed the presence of a de novo 3.6-Mb interstitial microdeletion in 8p23.1. The main features of 8p23.1 DS include congenital heart disease and behavioral problems, in addition to minor dysmorphisms and mental delay. Therefore, this article highlights the application of aGH to investigate 8p23.1 deletion in nonconfirmed 22q11.2 DS patients presenting neurobehavioral disorders, congenital cardiopathy, and minor dysmorphisms.

  8. Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome

    PubMed Central

    Mlynarski, Elisabeth E.; Sheridan, Molly B.; Xie, Michael; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Gai, Xiaowu; Chow, Eva W.C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Shaikh, Tamim H.; Bassett, Anne S.; Goldmuntz, Elizabeth; Morrow, Bernice E.; Emanuel, Beverly S.

    2015-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10−3, two-tailed Fisher’s exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10−2, two-tailed Fisher’s exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10−4, two-tailed Fisher’s exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS. PMID:25892112

  9. MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del

    PubMed Central

    Zhao, Dejian; Lin, Mingyan; Chen, Jian; Pedrosa, Erika; Hrabovsky, Anastasia; Fourcade, H. Matthew; Zheng, Deyou; Lachman, Herbert M.

    2015-01-01

    We are using induced pluripotent stem cell (iPSC) technology to study neuropsychiatric disorders associated with 22q11.2 microdeletions (del), the most common known schizophrenia (SZ)-associated genetic factor. Several genes in the region have been implicated; a promising candidate is DGCR8, which codes for a protein involved in microRNA (miRNA) biogenesis. We carried out miRNA expression profiling (miRNA-seq) on neurons generated from iPSCs derived from controls and SZ patients with 22q11.2 del. Using thresholds of p<0.01 for nominal significance and 1.5-fold differences in expression, 45 differentially expressed miRNAs were detected (13 lower in SZ and 32 higher). Of these, 6 were significantly down-regulated in patients after correcting for genome wide significance (FDR<0.05), including 4 miRNAs that map to the 22q11.2 del region. In addition, a nominally significant increase in the expression of several miRNAs was found in the 22q11.2 neurons that were previously found to be differentially expressed in autopsy samples and peripheral blood in SZ and autism spectrum disorders (e.g., miR-34, miR-4449, miR-146b-3p, and miR-23a-5p). Pathway and function analysis of predicted mRNA targets of the differentially expressed miRNAs showed enrichment for genes involved in neurological disease and psychological disorders for both up and down regulated miRNAs. Our findings suggest that: i. neurons with 22q11.2 del recapitulate the miRNA expression patterns expected of 22q11.2 haploinsufficiency, ii. differentially expressed miRNAs previously identified using autopsy samples and peripheral cells, both of which have significant methodological problems, are indeed disrupted in neuropsychiatric disorders and likely have an underlying genetic basis. PMID:26173148

  10. A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

    PubMed Central

    SIMON, TONY J.; BISH, JOEL P.; BEARDEN, CARRIE E.; DING, LIJUN; FERRANTE, SAMANTHA; NGUYEN, VY; GEE, JAMES C.; McDONALD–McGINN, DONNA M.; ZACKAI, ELAINE H.; EMANUEL, BEVERLY S.

    2006-01-01

    We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. PMID:16262991

  11. Mapping of a Gene Determining Familial Partial Epilepsy with Variable Foci to Chromosome 22q11-q12

    PubMed Central

    Xiong, Lan; Labuda, Malgorzata; Li, Dong-Sheng; Hudson, Thomas J.; Desbiens, Richard; Patry, Georges; Verret, Simon; Langevin, Pierre; Mercho, Suha; Seni, Marie-Hélène; Scheffer, Ingrid; Dubeau, François; Berkovic, Samuel F.; Andermann, Frederick; Andermann, Eva; Pandolfo, Massimo

    1999-01-01

    Summary We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3.8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (θ) 0 with D22S689. The LOD score in the larger family was 5.34 at θ=0 with the same marker. The two families share an identical linked haplotype for ⩾10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF. PMID:10577924

  12. Overlapping Numerical Cognition Impairments In Children With Chromosome 22q11.2 Deletion Or Turner Syndromes

    PubMed Central

    Simon, T.J.; Takarae, Y.; DeBoer, T.; McDonald-McGinn; Zackai, E.H.; Ross, J.L.

    2008-01-01

    Children with one of two genetic disorders (chromosome 22q11.2 deletion syndrome and Turner syndrome) as well typically developing controls, participated in three cognitive processing experiments. Two experiments were designed to test cognitive processes involved in basic aspects numerical cognition. The third was a test of simple manual motor reaction time. Despite significant differences in global intellectual abilities, as measured by IQ tests, performance on the two numerical cognition tasks differed little between the two groups of children with genetic disorders. However, both performed significantly more poorly than did controls. The pattern of results are consistent with the hypothesis that impairments were not due to global intellectual ability but arose in specific cognitive functions required by different conditions within the tasks. The fact that no group differences were found in the reaction time task, despite significant differences in the standardized processing speed measure, further supports the interpretation that specific cognitive processing impairments and not global intellectual or processing speed impairments explain the pattern of results. The similarity in performance on these tasks of children with unrelated genetic disorders counters the view that numerical cognition is under any direct genetic control. Instead, our findings are consistent with the view that disturbances in foundational spatiotemporal cognitive functions contribute to the development of atypical representations and processes in the domains of basic magnitude comparison and simple numerical enumeration. PMID:17920087

  13. Familial DiGeorge/velocardiofacial syndrome with deletions of chromosome area 22q11.2: Report of five families with a review of the literature

    SciTech Connect

    Leana-Cox, J.; Pangkanon, Suthipong; Eanet, K.R.

    1996-11-11

    The DiGeorge (DG), velocardiofacial (VCF), and conotruncal anomaly-face (CTAF) syndromes were originally described as distinct disorders, although overlapping phenotypes have been recognized. It is now clear that all three syndromes result from apparently similar or identical 22q11.2 deletions, suggesting that they represent phenotypic variability of a single genetic syndrome. We report on 12 individuals in five families with del(22)(q11.2) by fluorescent in situ hybridization, and define the frequency of phenotypic abnormalities in those cases and in 70 individuals from 27 del(22)(q11.2) families from the literature. Common manifestations include mental impairment (97%), abnormal face (93%), cardiac malformations (681%), thymic (64%) and parathyroid (63%) abnormalities, and cleft palate or velopharyngeal insufficiency (48%). Familial DG, VCF, and CTAF syndromes due to del(22)(q11.2) show significant inter- and intrafamilial clinical variability consistent with the hypothesis that a single gene or group of tightly linked genes is the common cause of these syndromes. Up to 25% of 22q deletions are inherited, indicating that parents of affected children warrant molecular cytogenetic evaluation. We propose use of the compound term {open_quotes}DiGeorge/velocardiofacial (DGNCF) syndrome{close_quotes} in referring to this condition, as it calls attention to the phenotypic spectrum using historically familiar names. 41 refs., 2 figs., 2 tabs.

  14. Hemifacial microsomia in cat-eye syndrome: 22q11.1-q11.21 as candidate loci for facial symmetry.

    PubMed

    Quintero-Rivera, Fabiola; Martinez-Agosto, Julian A

    2013-08-01

    Cat-Eye syndrome (CES), (OMIM 115470) also known as chromosome 22 partial tetrasomy or inverted duplicated 22q11, was first reported by Haab [1879] based on the primary features of eye coloboma and anal atresia. However, >60% of the patients lack these primary features. Here, we present a 9-month-old female who at birth was noted to have multiple defects, including facial asymmetry with asymmetric retrognathia, bilateral mandibular hypoplasia, branchial cleft sinus, right-sided muscular torticollis, esotropia, and an atretic right ear canal with low-to-moderate sensorineural hearing loss, bilateral preauricular ear tag/pits, and two skin tags on her left cheek. There were no signs of any colobomas or anal atresia. Hemifacial microsomia (HFM) was suspected clinically. Chromosome studies and FISH identified an extra marker originated from 22q11 consistent with CES, and this was confirmed by aCGH. This report expands the phenotypic variability of CES and includes partial tetrasomy of 22q11.1-q11.21 in the differential diagnosis of HFM. In addition, our case as well as the previous association of 22q11.2 deletions and duplications with facial asymmetry and features of HFM, supports the hypothesis that this chromosome region harbors genes important in the regulation of body plan symmetry, and in particular facial harmony. PMID:23794175

  15. Investigation of TBX1 gene deletion in Iranian children with 22q11.2 deletion syndrome: correlation with conotruncal heart defects

    PubMed Central

    Ganji, Hamid; Salehi, Mansoor; Sedghi, Maryam; Abdali, Hossein; Nouri, Nayereh; Sadri, Leyli; Hosseinzadeh, Majid; Vakili, Bahareh; Lotfi, Mahdi

    2013-01-01

    Background DiGeorge syndrome (DGS) is the result of a microdeletion in chromosome 22q11.2 in over 90% of cases. DGS is the second most frequent syndrome after Down syndrome and has an incidence of 1/4000 births. Unequal crossover between low-copy repeats, on the proximal part of the long arm of chromosome 22, usually results in a 3 Mb deletion in one of the chromosome 22 and a reciprocal and similarly sized duplication on the other one. Several studies have indicated that TBX1 (T-box 1) haploinsufficiency is responsible for many of the phenotypic traits of 22q11.2 deletion syndrome. Conotruncal heart defects (CTDs) are present in 75–85% of patients with 22q11.2 deletion syndrome in Western countries. Methods Among 78 patients fulfilling the criteria for DGS diagnosed by the fluorescence in situ hybridisation test, 24 had 22q11.2 deletion. Screening for TBX1 gene deletion was performed by multiplex ligation-dependent probe amplification (MLPA). Results Our results revealed that of 24 patients with TBX1 gene deletion, 12 had CTDs while 12 did not show any heart defects. Conclusions Our findings indicate that other genes or gene interactions may play a role in penetrance or the severity of heart disease among patients with DGS. PMID:27326128

  16. A New Account of the Neurocognitive Foundations of Impairments in Space, Time, and Number Processing in Children with Chromosome 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Simon, Tony J.

    2008-01-01

    In this article, I present an updated account that attempts to explain, in cognitive processing and neural terms, the nonverbal intellectual impairments experienced by most children with deletions of chromosome 22q11.2. Specifically, I propose that this genetic syndrome leads to early developmental changes in the structure and function of clearly…

  17. The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome

    PubMed Central

    Muldoon, Meghan; Ousley, Opal Y.; Kobrynski, Lisa J.; Patel, Sheena; Oster, Matthew E.; Fernandez-Carriba, Samuel; Cubells, Joseph F.; Coleman, Karlene; Pearce, Bradley D.

    2014-01-01

    22q11 deletion syndrome (22qDS), also known as DiGeorge Syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p<0.05), Speech (p<0.01), and Symbolic domains (p<0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes. PMID:25267002

  18. Two Functional Copies of the DGCR6 Gene Are Present on Human Chromosome 22q11 Due to a Duplication of an Ancestral Locus

    PubMed Central

    Edelmann, Lisa; Stankiewicz, Pavel; Spiteri, Elizabeth; Pandita, Raj K.; Shaffer, Lisa; Lupski, James; Morrow, Bernice E.

    2001-01-01

    The DGCR6 (DiGeorge critical region) gene encodes a putative protein with sequence similarity to gonadal (gdl), a Drosophila melanogaster gene of unknown function. We mapped the DGCR6 gene to chromosome 22q11 within a low copy repeat, termed sc11.1a, and identified a second copy of the gene, DGCR6L, within the duplicate locus, termed sc11.1b. Both sc11.1 repeats are deleted in most persons with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), and they map immediately adjacent and internal to the low copy repeats, termed LCR22, that mediate the deletions associated with VCFS/DGS. We sequenced genomic clones from both loci and determined that the putative initiator methionine is located further upstream than originally described, but in a position similar to the mouse and chicken orthologs. DGCR6L encodes a highly homologous, functional copy of DGCR6, with some base changes rendering amino acid differences. Expression studies of the two genes indicate that both genes are widely expressed in fetal and adult tissues. Evolutionary studies using FISH mapping in several different species of ape combined with sequence analysis of DGCR6 in a number of different primate species indicate that the duplication is at least 12 million years old and may date back to before the divergence of Catarrhines from Platyrrhines, 35 mya. These data suggest that there has been selective evolutionary pressure toward the functional maintenance of both paralogs. Interestingly, a full-length HERV-K provirus integrated into the sc11.1a locus after the divergence of chimpanzees and humans. PMID:11157784

  19. Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: Comorbidity predicts behavioural difficulties and impaired functional communications

    PubMed Central

    Stephenson, David D.; Beaton, Elliott A.; Weems, Carl F.; Angkustsiri, Kathleen; Simon, Tony J.

    2014-01-01

    Background Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex genetic disorder with a variable clinical presentation that can include cardiac, neural, immunological, and psychological issues. Previous studies have measured elevated anxiety and depression in children with 22q11.2DS. Comorbity of anxiety and depression is well established in the pediatric literature but the nature of comorbidity patterns has not been empirically established in children with 22q11.2DS. Comorbidity of anxiety and depression has important implications for treatment and prognosis, and may be a marker of risk in this population of children at high-risk for developing schizophrenia. Method Participants were 131 boys and girls ages 8 to 14 with (n = 76) and without (n = 55) 22q11.2DS and their mothers. Children and mothers independently completed self- and parent-report measures of anxiety and depression. Mothers also completed measures of behavioural functioning including the Behavioral Assessment for Children, 2nd ed. (BASC-2). Cluster analyses were conducted to test if theoretically based groupings of anxiety and depression could be identified. We hypothesized four psychological profiles based on child- and mother-reports: low/no anxiety and low/no depression, higher depression and low/no anxiety, higher anxiety and no/low depression, and a comorbid profile of higher anxiety and higher depression. BASC-2 subscale scores were then compared across subgroups of children to determine if a comorbid profile would predict greater behavioural difficulties. Results In the full sample of children both with and without 22q11.2DS, cluster analyses of self and maternal reported anxiety and depression revealed the expected subgroups: 1) a group of children with higher anxiety/lower depression (anxious); 2) a group with primary depression (lower anxiety/higher depression (depressed); 3) a comorbid group with higher anxiety/higher depression (comorbid); and, 4) a lowest anxiety

  20. Clinical experience with single‐nucleotide polymorphism‐based non‐invasive prenatal screening for 22q11.2 deletion syndrome

    PubMed Central

    Gross, S. J.; Stosic, M.; McDonald‐McGinn, D. M.; Bassett, A. S.; Norvez, A.; Dhamankar, R.; Kobara, K.; Kirkizlar, E.; Zimmermann, B.; Wayham, N.; Babiarz, J. E.; Ryan, A.; Jinnett, K. N.; Demko, Z.

    2016-01-01

    ABSTRACT Objectives To evaluate the performance of a single‐nucleotide polymorphism (SNP)‐based non‐invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow‐up and review patient choices for women with high‐risk results. Methods In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP‐based NIPT and subsequently evaluated. Follow‐up was conducted for all cases with a high‐risk result. Results Ninety‐five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high‐risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true‐positive and 18.0% of false‐positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing. Conclusions Clinical experience with this SNP‐based non‐invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high‐risk pregnancies. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. PMID:26396068

  1. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    PubMed

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period.

  2. 22q11.2 Deletion Syndrome due to a Translocation t(6;22) in a Patient Conceived via in vitro Fertilization

    PubMed Central

    Gollo Dantas, Anelisa; Bortolai, Adriana; Moysés-Oliveira, Mariana; Takeno Herrero, Sylvia; Azoubel Antunes, Adriana; Tavares Costa-Carvalho, Beatriz; Ayres Meloni, Vera; Melaragno, Maria Isabel

    2016-01-01

    We report on a patient conceived via in vitro fertilization (IVF) with a 22q11.2 deletion due to an unusual unbalanced translocation involving chromosomes 6 and 22 in a karyotype with 45 chromosomes. Cytogenomic studies showed that the patient has a 3.3-Mb deletion of chromosome 22q and a 0.4-Mb deletion of chromosome 6p, which resulted in haploinsufficiency of the genes responsible for the 22q11.2 deletion syndrome and also of the IRF4 gene, a member of the interferon regulatory factor family of transcription factors, which is expressed in the immune system cells. The rearrangement could be due to the manipulation of the embryo or as a sporadic event unrelated to IVF. Translocation involving chromosome 22 in a karyotype with 45 chromosomes is a rare event, with no previous reports involving chromosomes 6p and 22q. PMID:26997945

  3. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    PubMed

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period. PMID:27617133

  4. Hypoparathyroidism associated with aneurysm of the left subclavian artery (Kommerell's diverticulum) in an adult patient with a chromosome 22q11.2 deletion.

    PubMed

    Trombetti, A; Bottani, A; George, F; Rizzoli, R

    2001-10-01

    Hypoparathyroidism may either be acquired or of congenital origin. From the latter group, which represents a minority of cases, agenesis or hypoplasia of the parathyroid glands resulting in symptomatic hypocalcemia in the newborn or infant frequently is caused by a microdeletion of chromosome 22q11.2. We describe a man in whom hypoparathyroidism was first diagnosed at the age of 59 years. The endocrine disorder was found to be associated with this chromosome imbalance and also with an aneurysm of the left subclavian artery (Kommerell's diverticulum) compressing the esophagus and trachea. Given the potential implication for genetic counseling, a 22q11.2 deletion should be considered in the differential diagnosis of adult patients with hypoparathyroidism of unknown origin and should be searched for by appropriate molecular cytogenetic technique.

  5. Kinematic Movement Strategies in Primary School Children with 22q11.2 Deletion Syndrome Compared to Age- and IQ-Matched Controls during Visuo-Manual Tracking

    ERIC Educational Resources Information Center

    Van Aken, Katrijn; Swillen, Ann; Beirinckx, Marc; Janssens, Luc; Caeyenberghs, Karen; Smits-Engelsman, Bouwien

    2010-01-01

    The present study focused on the mechanism subserving the production of kinematic patterns in 21 children with 22q11.2DS (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.05 [plus or minus] 10.2) and 21 age- and IQ-matched control children (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.38 [plus or minus] 12.0) when performing a visuo-manual…

  6. White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging

    PubMed Central

    Villalon, Julio; Jahanshad, Neda; Beaton, Elliott; Toga, Arthur W.; Thompson, Paul M.; Simon, Tony J.

    2014-01-01

    Children with chromosome 22q11.2 Deletion Syndrome (22q11.2DS), Fragile X Syndrome (FXS), or Turner Syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14 years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders. PMID:23602925

  7. Explaining the variable penetrance of CNVs: Parental intelligence modulates expression of intellectual impairment caused by the 22q11.2 deletion.

    PubMed

    Klaassen, Petra; Duijff, Sasja; Swanenburg de Veye, Henriëtte; Beemer, Frits; Sinnema, Gerben; Breetvelt, Elemi; Schappin, Renske; Vorstman, Jacob

    2016-09-01

    The role of rare genetic variants, in particular copy number variants (CNVs), in the etiology of neurodevelopmental disorders is becoming increasingly clear. While the list of these disorder-related CNVs continues to lengthen, it has also become clear that in nearly all genetic variants the proportion of carriers who express the associated phenotype is far from 100%. To understand this variable penetrance of CNVs it is important to realize that even the largest CNVs represent only a tiny fraction of the entire genome. Therefore, part of the mechanism underlying the variable penetrance of CNVs is likely the modulatory impact of the rest of the genome. In the present study we used the 22q11DS as a model to examine whether the observed penetrance of intellectual impairment-one of the main phenotypes associated with 22q11DS-is modulated by the intellectual level of their parents, for which we used the parents' highest level of education as a proxy. Our results, based on data observed in 171 children with 22q11DS in the age range of 5-15 years, showed a significant association between estimated parental cognitive level and intelligence in offspring (full scale, verbal and performance IQ), with the largest effect size for verbal IQ. These results suggest that possible mechanisms involved in the variable penetrance observed in CNVs include the impact of genetic background and/or environmental influences. © 2016 Wiley Periodicals, Inc.

  8. Explaining the variable penetrance of CNVs: Parental intelligence modulates expression of intellectual impairment caused by the 22q11.2 deletion.

    PubMed

    Klaassen, Petra; Duijff, Sasja; Swanenburg de Veye, Henriëtte; Beemer, Frits; Sinnema, Gerben; Breetvelt, Elemi; Schappin, Renske; Vorstman, Jacob

    2016-09-01

    The role of rare genetic variants, in particular copy number variants (CNVs), in the etiology of neurodevelopmental disorders is becoming increasingly clear. While the list of these disorder-related CNVs continues to lengthen, it has also become clear that in nearly all genetic variants the proportion of carriers who express the associated phenotype is far from 100%. To understand this variable penetrance of CNVs it is important to realize that even the largest CNVs represent only a tiny fraction of the entire genome. Therefore, part of the mechanism underlying the variable penetrance of CNVs is likely the modulatory impact of the rest of the genome. In the present study we used the 22q11DS as a model to examine whether the observed penetrance of intellectual impairment-one of the main phenotypes associated with 22q11DS-is modulated by the intellectual level of their parents, for which we used the parents' highest level of education as a proxy. Our results, based on data observed in 171 children with 22q11DS in the age range of 5-15 years, showed a significant association between estimated parental cognitive level and intelligence in offspring (full scale, verbal and performance IQ), with the largest effect size for verbal IQ. These results suggest that possible mechanisms involved in the variable penetrance observed in CNVs include the impact of genetic background and/or environmental influences. © 2016 Wiley Periodicals, Inc. PMID:26953189

  9. Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome

    PubMed Central

    Bedeschi, M.F.; Colombo, L.; Mari, F.; Hofmann, K.; Rauch, A.; Gentilin, B.; Renieri, A.; Clerici, D.

    2011-01-01

    Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation. PMID:22140376

  10. Histology of the Pharyngeal Constrictor Muscle in 22q11.2 Deletion Syndrome and Non-Syndromic Children with Velopharyngeal Insufficiency

    PubMed Central

    Widdershoven, Josine C. C.; Spruijt, Nicole E.; Spliet, Wim G. M.; Breugem, Corstiaan C.; Kon, Moshe; Mink van der Molen, Aebele B.

    2011-01-01

    Plastic surgeons aim to correct velopharyngeal insufficiency manifest by hypernasal speech with a velopharyngoplasty. The functional outcome has been reported to be worse in patients with 22q11.2 deletion syndrome than in patients without the syndrome. A possible explanation is the hypotonia that is often present as part of the syndrome. To confirm a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome, specimens of the pharyngeal constrictor muscle were taken from children with and without the syndrome. Histologic properties were compared between the groups. Specimens from the two groups did not differ regarding the presence of increased perimysial or endomysial space, fiber grouping by size or type, internalized nuclei, the percentage type I fibers, or the diameters of type I and type II fibers. In conclusion, a myogenic component of the etiology of velopharyngeal insufficiency in children with 22q11.2 deletion syndrome could not be confirmed. PMID:21738760

  11. Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old man: a case report

    PubMed Central

    Tonelli, Adriano R; Kosuri, Kalyan; Wei, Sainan; Chick, Davoren

    2007-01-01

    Background The microdeletion of chromosome 22q11.2 is the most common human deletion syndrome. It typically presents early in life and is rarely considered in adult patients. As part of the manifestations of this condition, patients can have parathyroid glandular involvement ranging from hypocalcemic hypoparathyroidism to normocalcemia with normal parathryroid hormone levels. The first manifestation of the syndrome might be seizures due to profound hypocalcemia. Case presentation A 40-year-old man without significant past medical history presented with a new-onset generalized tonic-clonic seizure. He had no personal history of hypocalcemia or seizures. Physical examination was remarkable for short stature, hypertelorism, prominent forehead and nasal voice. His initial laboratory examination showed hypocalcemia (Calcium 5.2 mg/dl and Calcium ionized 0.69 mmol/l) with hypoparathyroidism (Parathyroid hormone intact < 2.5 pg/ml. NV: 14–72 pg/ml). Urine Calcium was 3 mg/dl on a spot and 88 mg in a 24-hour urine collection (NV: 100–300 mg/24 hs). The electrocardiogram showed a prolonged corrected QT interval. Echocardiogram, abdominal ultrasound and electroencephalogram were normal. A computer tomography of the brain showed basal ganglia calcification. The subtle physical findings and the presence of idiopathic hypoparathyroidism motivated the performance of fluorescent in situ hybridization which demonstrated a microdeletion on one of the homologs 22q11.2. The patient was treated with calcium citrate and calcitriol with good response. Conclusion Microdeletion of chromosome 22q11.2 is among the most clinically variable syndromes, with more than 180 features associated with the deletion. It has a variable phenotypical expression, requiring a high level of awareness for its early diagnosis. Seizures, related to marked hypocalcemia due to idiopathic hypoparathyroidism, might be the presenting feature in an adult patient with this syndrome. PMID:18053182

  12. Self-Reported Speech Problems in Adolescents and Young Adults with 22q11.2 Deletion Syndrome: A Cross-Sectional Cohort Study

    PubMed Central

    Vorstman, Jacob AS; Kon, Moshe; Mink van der Molen, Aebele B

    2014-01-01

    Background Speech problems are a common clinical feature of the 22q11.2 deletion syndrome. The objectives of this study were to inventory the speech history and current self-reported speech rating of adolescents and young adults, and examine the possible variables influencing the current speech ratings, including cleft palate, surgery, speech and language therapy, intelligence quotient, and age at assessment. Methods In this cross-sectional cohort study, 50 adolescents and young adults with the 22q11.2 deletion syndrome (ages, 12-26 years, 67% female) filled out questionnaires. A neuropsychologist administered an age-appropriate intelligence quotient test. The demographics, histories, and intelligence of patients with normal speech (speech rating=1) were compared to those of patients with different speech (speech rating>1). Results Of the 50 patients, a minority (26%) had a cleft palate, nearly half (46%) underwent a pharyngoplasty, and all (100%) had speech and language therapy. Poorer speech ratings were correlated with more years of speech and language therapy (Spearman's correlation= 0.418, P=0.004; 95% confidence interval, 0.145-0.632). Only 34% had normal speech ratings. The groups with normal and different speech were not significantly different with respect to the demographic variables; a history of cleft palate, surgery, or speech and language therapy; and the intelligence quotient. Conclusions All adolescents and young adults with the 22q11.2 deletion syndrome had undergone speech and language therapy, and nearly half of them underwent pharyngoplasty. Only 34% attained normal speech ratings. Those with poorer speech ratings had speech and language therapy for more years. PMID:25276637

  13. Unmasking an autosomal recessive disorder by a deletion in the DiGeorge/Velo-cardio-facial chromosome region (DGCR) in 22q11.2

    SciTech Connect

    Budarf, M.L.; Michaud, D.; Emanuel, B.

    1994-09-01

    Unmasking an autosomal recessive disorder by constitutional hemizygosity is well documented for the embryonal tumors RB and WAGR, where the second hit is a somatic event. Few deletion-mediated recessive conditions have been reported in patients with germline mutations. The major platelet receptor for von Willebrand factor, Glycoprotein Ib (GpIb), is a complex of two plasma membrane glycoproteins, Ib{alpha} and Ib{beta}, covalently linked by disulfide bonds. Defects in this receptor have been associated with the rare congenital autosomal recessive bleeding disorder, Bernard-Soulier syndrome (BSS). BSS is characterized by prolonged bleeding times, thrombocytopenia and very large platelets. The GpIb{beta} gene has been cloned and we have mapped it within the DGCR. We have identified a patient with phenotypic features of both BSS and VCFS. The patient was referred for 22q11-deletion FISH studies because of a conventricular VSD and mild dysmorphia. FISH with the N25 DiGeorge cosmid demonstrated a deletion in 22q11.2. Western blot analysis of the patient`s platelet proteins demonstrates a complete absence of GpIb{beta}. We suggest that haploinsufficiency for the DGCR in this patient unmasks a mutation in the remaining GpIb{beta} allele, resulting in manifestations of BSS. This mechanism, haploinsufficiency coupled with a mutation of the {open_quotes}normal{close_quotes} chromosome, might explain some of the phenotypic variability seen amongst patients with 22q11.2 microdeletions. These results further suggest that patients with contiguous gene deletion syndromes are at increased risk for autosomal recessive disorders and that they provide the opportunity to {open_quotes}map{close_quotes}disease loci.

  14. Inherited and de novo 22q11.2 distal duplications in two patients with autistic features, speech delay and no dysmorphology

    PubMed Central

    Hantash, Feras M.; Wang, Boris T.; Owen, Renius; Ross, Leslie P.; Mahon, Loretta W.; Boyar, Fatih Z.; Anguiano, Arturo; Strom, Charles M.

    2012-01-01

    In a screen of patients by fluorescence in-situ hybridization and array comparative genomic hybridization in the past two years (July 2007--July 2009), we identified two patients with duplications in the 22q11.22-23, occurring outside the common DiGeorge syndrome/valocardiofacial syndrome region. Fluorescent in-situ hybridization, multiplex ligation-dependent probe amplification and high density bacterial artificial chromosomes and oligo arrays were used to identify the extent of the duplications. In one patient the duplication extended from LCR22-E/5 to LCR22-H/8, which is similar to recently described 22q11.2 distal duplications, while in the second patient, a de novo duplication was identified extending between LCR22-E/5 to LCR22-F/6. The second proband also harbored a de novo 15q14 duplication, complicating phenotype interpretation. The patients were affected with speech delay and autistic features, but neither reported cardiac concern or dysmorphic features.

  15. Uveitis in DiGeorge syndrome: a case of autoimmune ocular inflammation in a patient with deletion 22q11.2

    PubMed Central

    Gottlieb, Chloe; Li, Zhuqing; Uzel, Gulbu; Nussenblatt, Robert B; Sen, H Nida

    2010-01-01

    Purpose Del22q11.2, also known as DiGeorge syndrome, has a spectrum of ocular, facial and systemic features. Despite features of T cell dysfunction, infection and autoimmunity (including juvenile idiopathic arthritis), uveitis has not been described in patients with DiGeorge syndrome. Methods We describe a case of a 25-year-old male with bilateral granulomatous panuveitis who after initial investigation and treatment for an infectious cause was determined to have autoimmune-related uveitis with evidence on clinical, laboratory and imaging assessments suggestive of ocular sarcoidosis. Results The patient was found to have a normal T cell count and T cell proliferative response that was compared to a control patient, and phenotypes determined by flow cytometry were normal. However, the CD4/CD8 ratio in this patient was slightly lower than normal and the number of CD28 negative T cells, in both CD4 and CD8 populations, were significantly higher than a control. Conclusions The significance of these T cell abnormalities is unknown in the context of this patient’s uveitis but is suggestive of a role in autoimmunity, which is a known phenomenon in del22q11.2 syndrome, although autoimmune-related uveitis is not a previously described feature. PMID:20141355

  16. Inherited and de novo 22q11.2 distal duplications in two patients with autistic features, speech delay and no dysmorphology.

    PubMed

    Hantash, Feras M; Wang, Boris T; Owen, Renius; Ross, Leslie P; Mahon, Loretta W; Boyar, Fatih Z; Anguiano, Arturo; Strom, Charles M

    2012-06-01

    In a screen of patients by fluorescence in-situ hybridization and array comparative genomic hybridization in the past two years (July 2007--July 2009), we identified two patients with duplications in the 22q11.22-23, occurring outside the common DiGeorge syndrome/valocardiofacial syndrome region. Fluorescent in-situ hybridization, multiplex ligation-dependent probe amplification and high density bacterial artificial chromosomes and oligo arrays were used to identify the extent of the duplications. In one patient the duplication extended from LCR22-E/5 to LCR22-H/8, which is similar to recently described 22q11.2 distal duplications, while in the second patient, a de novo duplication was identified extending between LCR22-E/5 to LCR22-F/6. The second proband also harbored a de novo 15q14 duplication, complicating phenotype interpretation. The patients were affected with speech delay and autistic features, but neither reported cardiac concern or dysmorphic features. PMID:27625811

  17. The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD.

    PubMed

    Richard, Anne Claire; Rovelet-Lecrux, Anne; Delaby, Elsa; Charbonnier, Camille; Thiruvahindrapuram, Bhooma; Hatchwell, Eli; Eis, Peggy S; Afenjar, Alexandra; Dussardier, Brigitte Gilbert; Scherer, Stephen W; Betancur, Catalina; Campion, Dominique

    2016-04-01

    The proline dehydrogenase (PRODH) gene maps to 22q11.2 in the region deleted in the velo-cardio-facial syndrome (VCFS). A moderate to severe reduction (>50%) in PRODH activity resulting from recessive deletions and/or missense mutations has been shown to cause type 1 hyperprolinemia (HPI). Autistic features have been reported as a common clinical manifestation of HPI. Here we studied the frequency of a recurrent small 22q11.2 deletion encompassing PRODH and the neighboring DGCR6 gene in three case-control studies, one comprising HPI patients (n = 83), and the other two comprising autism spectrum disorder (ASD) patients (total of n = 2800), analyzed with high-resolution microarrays. We found that the PRODH deletion is a strong risk factor for HPI (OR = 50.7; 95%CI = 7.5-2147) but not for ASD (P = 0.4, OR = 0.6-3.3). This result indicates either that the suggested association between ASD and HPI is spurious and results from a bias leading to the preferential inclusion of patients with autistic features in HPI series, or that HPI is present in only a very small subset of ASD patients. In this latter case, a very large sample size would be required to detect an association between the PRODH deletion and ASD in a case-control study.

  18. Velopharyngeal incompetence diagnosed in a series of cardiac patients prompted by the finding of a 22q11.2 deletion

    SciTech Connect

    Driscoll, D.A.; Emanuel, B.S.; Goldmuntz, E.

    1994-09-01

    Congenital heart disease is very common and may occur as an isolated malformation or as part of a well-defined syndrome. In some syndromes, specific types are overrepresented as compared to their incidence in the general population. Conotruncal anomalies are one such example where they are seen as part of DiGeorge syndrome (DGS) and Velo-Cardio-Facial syndrome (VCFS). Often, the diagnosis of VCFS is not suspected because mild facial dysmorphia is frequently not appreciated in the newborn period. While overt cleft palate, a characteristic finding in VCFS, would be detected early, a submucousal cleft palate or velopharyngeal incompetence (VPI) may go unrecognized in the pre-verbal child and may remain undiagnosed in the older patient who is not referred for a palatal evaluation. In patients with either DGS or VCFS, microdeletions of chromosome 22q11.2 have been demonstrated in almost 90% of patients. As part of our ongoing study, twenty patients with a conotruncal cardiac anomaly, without an overt cleft palate, were referred for 22q11.2 deletion analysis. 13/20 patients were found to have a deletion. All 13 deleted patients underwent palatal evaluations by a plastic surgeon and speech pathologist. 7 patients were noted to have VPI. Intervention including speech therapy and/or posterior pharyngeal flap surgery for these previously undiagnosed abnormalities is underway. These results suggest that palatal abnormalities are underdiagnosed in a significant proportion of patients with conotruncal cardiac defects. We therefore propose deletion studies in these patients followed by prompt palatal evaluations when the deletion is present. Early diagnosis of VPI and submucousal cleft palate should lead to early intervention and appropriate management of the speech difficulties encountered by these individuals.

  19. Dopamine metabolism in adults with 22q11 deletion syndrome, with and without schizophrenia--relationship with COMT Val¹⁰⁸/¹⁵⁸Met polymorphism, gender and symptomatology.

    PubMed

    Boot, Erik; Booij, Jan; Abeling, Nico; Meijer, Julia; da Silva Alves, Fabiana; Zinkstok, Janneke; Baas, Frank; Linszen, Don; van Amelsvoort, Thérèse

    2011-07-01

    22q11 Deletion syndrome (22q11DS) is a major risk factor for schizophrenia. In addition, both conditions are associated with alterations of the dopaminergic system. The catechol-O-methyltransferase (COMT) gene, located within the deleted region, encodes for the enzyme COMT that is important for degradation of catecholamines, including dopamine (DA). COMT activity is sexually dimorphic and its gene contains a functional polymorphism, Val¹⁰⁸/¹⁵⁸ Met; the Met allele is associated with lower enzyme activity. We report the first controlled catecholamine study in 22q11DS-related schizophrenia. Twelve adults with 22q11DS with schizophrenia (SCZ+) and 22 adults with 22q11DS without schizophrenia (SCZ-) were genotyped for the COMT Val¹⁰⁸/¹⁵⁸ Met genotype. We assessed dopaminergic markers in urine and plasma. We also correlated these markers with scores on the Positive and Negative Symptom Scale (PANSS). Contrary to our expectations, we found SCZ+ subjects to be more often Val hemizygous and SCZ- subjects more often Met hemizygous. Significant COMT cross gender interactions were found on dopaminergic markers. In SCZ+ subjects there was a negative correlation between prolactin levels and scores on the general psychopathology subscale of the PANSS scores. These findings suggest intriguing, but complex, interactions of the COMT Val¹⁰⁸/¹⁵⁸ Met polymorphism, gender and additional factors on DA metabolism, and its relationship with schizophrenia.

  20. Identification of Proximal and Distal 22q11.2 Microduplications among Patients with Cleft Lip and/or Palate: A Novel Inherited Atypical 0.6 Mb Duplication

    PubMed Central

    Sedghi, Maryam; Abdali, Hossein; Memarzadeh, Mehrdad; Salehi, Mansoor; Nouri, Narges; Hosseinzadeh, Majid; Nouri, Nayereh

    2015-01-01

    Misalignments of low-copy repeats (LCRs) located in chromosome 22, particularly band 22q11.2, predispose to rearrangements. A variety of phenotypic features are associated with 22q11.2 microduplication syndrome which makes it challenging for the genetic counselors to recommend appropriate genetic assessment and counseling for the patients. In this study, multiplex ligation probe dependent amplification (MLPA) analysis was performed on 378 patients with cleft lip and/or palate to characterize rearrangements in patients suspected of 22q11.2 microduplication and microdeletion syndromes. Of 378 cases, 15 were diagnosed with a microdeletion with various sizes and 3 with duplications. For the first time in this study an atypical 0.6 Mb duplication is reported. Illustration of the phenotypes associated with the microduplications increases the knowledge of phenotypes reported in the literature. PMID:26640714

  1. Congenital stridor and wheezing as harbingers of the del22q11.2 syndrome presenting cardiovascular malformations of right aortic arch, aberrant left subclavian artery, Kommerell's diverticulum, and left ligamentum arteriosum.

    PubMed

    Lee, Meng-Luen; Chen, Ming; Tsao, Lon-Yen; Chiu, Han-Yao; Chiu, Ing-Sh; Yang, Albert D; Tsai, Pei-Ling

    2011-01-01

    A complete vascular ring composed of right aortic arch, aberrant left subclavian artery with Kommerell's diverticulum, and left ligamentum arteriosum was diagnosed by barium esophagography, echocardiography, angiography, and multidetector computed tomography of chest in an 18-day-old male neonate who presented with remarkable inspiratory stridor, expiratory wheezing, postprandial vomiting, and dysphagia since birth, and survived surgical division of the left ligamentum arteriosum, resection of the Kommerell's diverticulum, and reimplanation of the left subclavian artery to the left common carotid artery. Cytogenetic analysis and fluorescence in situ hybridization study of his blood revealed chromosome 22q11.2 deletion, with a karyotype of 46,XY.ish del(22)(q11.2 q11.2). A constellation of right aortic arch, aberrant left subclavian artery with Kommerell's diverticulum, and left ligamentum arteriosum in neonates may cause refractory stridor, wheezing, vomiting, and dysphagia, which can serve as harbingers of the del22q11.2 syndrome.

  2. Case history and genome-wide scans for copy number variants in a family with patient having 15q11.1-q11.2 duplication and 22q11.2 deletion, and schizophrenia.

    PubMed

    Takahashi, Sakae; Suzuki, Takahiro; Nakamura-Tomizuka, Sakura; Osaki, Koichi; Sotome, Yuta; Sagawa, Tomoaki; Uchiyama, Makoto

    2015-06-01

    Many studies have indicated that chromosomes 15q11 and 22q11 may be associated with the genetic etiologies of schizophrenia. We have followed an adult schizophrenia case with 15q11.1-q11.2 duplication and 22q11.2 deletion. Here we report his clinical history, and copy number variants (CNVs) identified by microarray and real-time PCR in the patient and his parents. This is the first report describing a detailed phenotype of an adult schizophrenic case with both 15q11 and 22q11 CNVs as revealed by novel and trustworthy technologies. Subjects were a 33-year-old male patient with 15q11 and 22q11 CNVs, and his normal parents. He fulfilled the DSM-IV criteria for schizophrenia at age 18 years. He was also diagnosed with 22q11.2 deletion syndrome by fluorescence in situ hybridization (FISH) at age 18 years. To search for CNVs in more detail, whole-genome array-CGH analyses including ∼ 420,000 probes were carried out in the patient and his parents. For validations of the CNVs detected by array-CGH, real-time PCR analyses of these CNVs were performed. The patient had two disease-specific CNVs, 15q11.1-q11.2 duplication (∼ 2.7 Mb) and 22q11.21 deletion (∼ 2.9 Mb). These two regions are important for the development of schizophrenia, and this patient had shown symptoms of schizophrenia. Thus, the two areas may contain causal genes for schizophrenia.

  3. Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study.

    PubMed

    Campbell, Linda E; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Catani, Marco; Ng, Virginia; van Amelsvoort, Therese; Chitnis, Xavier; Cutter, William; Murphy, Declan G M; Murphy, Kieran C

    2006-05-01

    In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly

  4. Pericentric inversion of chromosome 7 (inv(7) (p22q11.2)) and ring chromosome 8 (r(8) (p23q24.3)) in a girl with minor anomalies.

    PubMed Central

    Verma, R S; Conte, R A; Pitter, J H; Luke, S

    1992-01-01

    A 13 year old girl was referred with congenital microcephaly, developmental delay, a prominent nose, highly arched palate, and an apparently low set left ear. She was found to have a pericentric inversion of one chromosome 7 and a ring chromosome 8, 46,XX,inv(7) (pter----p22::q11.23----p22::q11.23----qter), r(8) (p23q24.3). The concurrence of these two abnormalities is a rare event and has not been reported previously. Images PMID:1552550

  5. Secondary EWSR1 Gene Abnormalities in SMARCB1-Deficient Tumors with 22q11-12 Regional Deletions: Potential Pitfalls in Interpreting EWSR1 FISH Results

    PubMed Central

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Kao, Yu-Chien; Agaram, Narasimhan P.; Antonescu, Cristina R.

    2016-01-01

    SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. PMID:27218413

  6. Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.

    PubMed

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Kao, Yu-Chien; Agaram, Narasimhan P; Antonescu, Cristina R

    2016-10-01

    SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc. PMID:27218413

  7. Definition of 5q11.2 microdeletion syndrome reveals overlap with CHARGE syndrome and 22q11 deletion syndrome phenotypes.

    PubMed

    Snijders Blok, Charlotte; Corsten-Janssen, Nicole; FitzPatrick, David R; Romano, Corrado; Fichera, Marco; Vitello, Girolamo Aurelio; Willemsen, Marjolein H; Schoots, Jeroen; Pfundt, Rolph; van Ravenswaaij-Arts, Conny M A; Hoefsloot, Lies; Kleefstra, Tjitske

    2014-11-01

    Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six patients with overlapping 5q11.2 deletions showed a phenotypic spectrum that overlaps with CHARGE syndrome and 22q11.2 deletion syndrome including choanal atresia, developmental delay, heart defects, external ear abnormalities, and short stature. No colobomas or abnormalities of semicircular canals and olfactory nerves were reported. Two male patients had genital abnormalities. We estimated a 2.0 Mb (53.0-55.0 Mb) Shortest Region of Overlap (SRO) for the main clinical characteristics of the syndrome. This region contains nine genes and two non-coding microRNAs. In this region DHX29 serves as the candidate gene as it encodes an ATP-dependent RNA-helicase that is involved in the initiation of RNA translation. Screening a small cohort of 14 patients who presented the main features, however, did not reveal any pathogenic abnormalities of DHX29.

  8. Anxiety Disorders and Perceptual Disturbances in Adolescents with 22q11.2 Deletion Syndrome Treated with SSRI: A Case Series

    PubMed Central

    Stachon, Andrea C.; De Souza, Claire

    2011-01-01

    Introduction: Psychotic symptoms are highly prevalent in adolescents with 22q11.2 Deletion Syndrome (22qDS), with as many as half reporting transient psychotic symptoms. Anxiety is also commonly seen in this population, and patients frequently report both psychotic symptoms and anxiety. Objective: To describe the psychiatric presentation, course and management of primary anxiety disorders in patients with 22qDS who also presented with isolated perceptual disturbances. Method: This report describes a 24-month clinical follow-up of three patients with 22qDS who were seen in the Medical Psychiatry clinic at the Hospital for Sick Children (Toronto, Canada). Results: Patients presented with primary anxiety disorders and perceptual disturbances. Patients were placed on selective serotonin reuptake inhibitor only, with improvement of both anxiety and perceptual disturbances being noted. Conclusions: Some patients with 22qDS who present with psychotic symptoms do not develop a psychotic disorder; therefore, the use of antipsychotics for every child or adolescent with 22qDS who experience psychotic symptoms is debatable. Long-term follow-up, phenomenological and treatment efficacy studies in larger samples are needed to determine optimal treatment of psychotic symptoms in children and adolescents with 22qDS. PMID:22114612

  9. Disclosure of psychiatric manifestations of 22q11.2 deletion syndrome in medical genetics: A 12-year retrospective chart review.

    PubMed

    Baughman, Serena Talcott; Morris, Emily; Jensen, Kimberly; Austin, Jehannine

    2015-10-01

    Individuals with 22q11.2 deletion syndrome (22qDS) have increased risk for psychiatric disorders. However, while medical geneticists self-report discussing psychiatric features of 22qDS with families (though often only when the child is older), most parents of children with 22qDS report receiving information about the psychiatric manifestations of 22qDS from non-medical sources. In an attempt to reconcile these previous findings, we sought to objectively determine the frequency with which medical geneticists discuss the potential psychiatric manifestations of 22qDS: (i) in letters to referring physicians and (ii) with families, and to explore plans for follow-up. We abstracted data from charts of patients with 22qDS who were referred to a single medical genetics center between January 1, 2000 and December 31, 2012. Psychiatric disorders were discussed in consult letters to referring physicians for n = 57 (46%) of the 125 patients who met inclusion criteria-making them less frequently discussed than all other features of 22qDS. Despite exhaustive review of charts, the content of discussions with families was typically unclear. Follow-up in medical genetics was suggested for 50 people but only 18 (36%) of these patients returned. Disclosure of psychiatric features of 22qDS to families is necessary so that psychiatric disorders can be identified in time for early intervention to be implemented to achieve better prognosis for those affected. These empiric data offer some explanation as to why psychiatric services are underused by individuals with 22qDS.

  10. Comparison of facial features of DiGeorge syndrome (DGS) due to deletion 10p13-10pter with DGS due to 22q11 deletion

    SciTech Connect

    Goodship, J.; Lynch, S.; Brown, J.

    1994-09-01

    DiGeorge syndrome (DGS) is a congenital anomaly consisting of cardiac defects, aplasia or hypoplasia of the thymus and parathroid glands, and dysmorphic facial features. The majority of DGS cases have a submicroscopic deletion within chromosome 22q11. However there have been a number of reports of DGS in association with other chromosomal abnormalities including four cases with chromosome 10p deletions. We describe a further 10p deletion case and suggest that the facial features in children with DGS due to deletions of 10p are different from those associated with chromosome 22 deletions. The propositus was born at 39 weeks gestation to unrelated caucasian parents, birth weight 2580g (10th centile) and was noted to be dysmorphic and cyanosed shortly after birth. The main dysmorphic facial features were a broad nasal bridge with very short palpebral fissures. Echocardiography revealed a large subsortic VSD and overriding aorta. She had a low ionised calcium and low parathroid hormone level. T cell subsets and PHA response were normal. Abdominal ultrasound showed duplex kidneys and on further investigation she was found to have reflux and raised plasma creatinine. She had an anteriorly placed anus. Her karyotype was 46,XX,-10,+der(10)t(3;10)(p23;p13)mat. The dysmorphic facial features in this baby are strikingly similar to those noted by Bridgeman and Butler in child with DGS as the result of a 10p deletion and distinct from the face seen in children with DiGeorge syndrome resulting from interstitial chromosome 22 deletions.

  11. In Search of the Optimal Surgical Treatment for Velopharyngeal Dysfunction in 22q11.2 Deletion Syndrome: A Systematic Review

    PubMed Central

    Spruijt, Nicole E.; ReijmanHinze, Judith; Hens, Greet; Vander Poorten, Vincent; Mink van der Molen, Aebele B.

    2012-01-01

    Background Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity. Methodology/ Principal Findings A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11–18% versus 44–62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7–13%, p = 0.03). Conclusions/ Significance In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to

  12. Clinical, cytogenetic, and molecular outcomes in a series of 66 patients with Pierre Robin sequence and literature review: 22q11.2 deletion is less common than other chromosomal anomalies.

    PubMed

    Gomez-Ospina, Natalia; Bernstein, Jonathan A

    2016-04-01

    Pierre Robin sequence (PRS) is an important craniofacial anomaly that can be seen as an isolated finding or manifestation of multiple syndromes. 22q11.2 deletion and Stickler syndrome are cited as the two most common conditions associated with PRS, but their frequencies are debated. We performed a retrospective study of 66 patients with PRS and reviewed their genetic testing, diagnoses, and clinical findings. The case series is complemented by a comprehensive literature review of the nature and frequency of genetic diagnosis in PRS. In our cohort 65% of patients had associated anomalies; of these, a genetic diagnosis was established in 56%. Stickler syndrome was the most common diagnosis, comprising approximately 11% of all cases, followed by Treacher Collins syndrome (9%). The frequency of 22q11.2 deletion was 1.5%. Chromosome arrays, performed for 72% of idiopathic PRS with associated anomalies, revealed two cases of 18q22→qter deletion, a region not previously reported in association with PRS. A review of the cytogenetic anomalies identified in this population supports an association between the 4q33-qter, 17q24.3, 2q33.1, and 11q23 chromosomal loci and PRS. We found a low frequency of 22q11.2 deletion in PRS, suggesting it is less commonly implicated in this malformation. Our data also indicate a higher frequency of cytogenetic anomalies in PRS patients with associated anomalies, and a potential new link with the 18q22→qter locus. The present findings underscore the utility of chromosomal microarrays in cases of PRS with associated anomalies and suggest that delaying testing for apparently isolated cases should be considered.

  13. Syndromes microdélétionnels (syndrome de Williams et syndrome de la délétion 22q11) au CHU Hassan II de Fès: à propos de 3 observations

    PubMed Central

    Ouldim, Karim; Bouguenouch, Laila; Samri, Imane; El Otmani, Ihsan; Hamdaoui, Hasna; Bennis, Sanae; Lakhdar, Mounia Idrissi; Chaouki, Sana; Atmani, Samir; Hida, Moustapha

    2012-01-01

    Les syndromes microdélétionnels sont définis par la présence d’une anomalie chromosomique de taille mineure (inférieure à 5 mégabases) ou aneusomie segmentaire, décelable par cytogénétique moléculaire (FISH : Fluorescent in Situ Hybridization). Les syndromes microdélétionnels représentent des syndromes cliniques avec des phénotypes suffisamment caractéristiques pour être reconnus cliniquement. Actuellement la FISH est la technique de choix pour rechercher ces syndromes. Plusieurs syndromes microdélétionnels peuvent être confirmés aisément, les plus recherchés sont Le syndrome de Williams (microdélétion en 7q11.23) et le syndrome de la délétion 22q11 (microdélétion en 22q11.2). Le syndrome de Williams est caractérisé par une anomalie du développement qui associe un retard psycho-moteur, une dysmorphie du visage évocatrice et un profil cognitif et comportemental spécifique, une sténose aortique supravalvulaire -SASV- le plus souvent. Le Syndrome de la délétion 22q11 se caractérise par l’association de plusieurs malformations d’expression variable: une cardiopathie congénitale de type conotroncal, une dysmorphie faciale discrète mais caractéristique et une hypoplasie du thymus et des parathyroïdes. Nous rapportons nos premières observations au CHU Hassan II confirmées par FISH : Syndrome de la délétion 22q11 (n:2) et un syndrome de Williams. Le but de cet article est la mise à jour de nos connaissances sur ces deux syndromes et la mise en valeur du rôle de la cytogénétique moléculaire dans le diagnostic et le conseil génétique des syndromes microdélétionnels. PMID:22368746

  14. TBX1 protein interactions and microRNA-96-5p regulation controls cell proliferation during craniofacial and dental development: implications for 22q11.2 deletion syndrome

    PubMed Central

    Gao, Shan; Moreno, Myriam; Eliason, Steven; Cao, Huojun; Li, Xiao; Yu, Wenjie; Bidlack, Felicitas B.; Margolis, Henry C.; Baldini, Antonio; Amendt, Brad A.

    2015-01-01

    T-box transcription factor TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS, DiGeorge syndrome/Velo-cardio-facial syndrome), whose phenotypes include craniofacial malformations such as dental defects and cleft palate. In this study, Tbx1 was conditionally deleted or over-expressed in the oral and dental epithelium to establish its role in odontogenesis and craniofacial developmental. Tbx1 lineage tracing experiments demonstrated a specific region of Tbx1-positive cells in the labial cervical loop (LaCL, stem cell niche). We found that Tbx1 conditional knockout (Tbx1cKO) mice featured microdontia, which coincides with decreased stem cell proliferation in the LaCL of Tbx1cKO mice. In contrast, Tbx1 over-expression increased dental epithelial progenitor cells in the LaCL. Furthermore, microRNA-96 (miR-96) repressed Tbx1 expression and Tbx1 repressed miR-96 expression, suggesting that miR-96 and Tbx1 work in a regulatory loop to maintain the correct levels of Tbx1. Cleft palate was observed in both conditional knockout and over-expression mice, consistent with the craniofacial/tooth defects associated with TBX1 deletion and the gene duplication that leads to 22q11.2DS. The biochemical analyses of TBX1 human mutations demonstrate functional differences in their transcriptional regulation of miR-96 and co-regulation of PITX2 activity. TBX1 interacts with PITX2 to negatively regulate PITX2 transcriptional activity and the TBX1 N-terminus is required for its repressive activity. Overall, our results indicate that Tbx1 regulates the proliferation of dental progenitor cells and craniofacial development through miR-96-5p and PITX2. Together, these data suggest a new molecular mechanism controlling pathogenesis of dental anomalies in human 22q11.2DS. PMID:25556186

  15. A rare case of trisomy 11q23.3-11q25 and trisomy 22q11.1-22q11.21.

    PubMed

    Zou, P-S; Li, H-F; Chen, L-S; Ma, M; Chen, X-H; Xue, D; Cao, D-H

    2016-01-01

    Partial duplication of the long arm of chromosome 11 and the partial trisomy of 22q are uncommon karyotypic abnormalities. Here, we report the case of a 6-year-old girl who showed partial trisomy of 11q and 22q, as a result of a maternal balanced reciprocal translocation (11;22), and exhibited dysmorphic features, severe intellectual disability, brain malformations, and speech delay related to this unique chromosomal abnormality. Array comparative genomic hybridization (array CGH) revealed a gain in copy number on the long arm of chromosome 11, spanning at least 18.22 Mb. Additionally, there was a gain in copy number on the long arm of chromosome 22, spanning at least 3.46 Mb. FISH analysis using a chromosome 11 short arm telomere probe (11p14.2), a chromosome 11 long arm telomere probe (11q24.3), and a chromosome 22 long arm telomere probe (22q13.33) confirmed the origin of the marker chromosome. It has been confirmed by the State Key Laboratory of Medical Genetics of China that this is the first reported instance of the karyotype 47,XX, +der(22)t(11;22)(q23.3;q11.1)mat in the world. Our study reports an additional case that can be used to further characterize and delineate the clinical ramifications of partial trisomy of 11q and 22q. PMID:27173335

  16. Autistic Spectrum Disorders in Velo-Cardio Facial Syndrome (22q11.2 Deletion)

    ERIC Educational Resources Information Center

    Antshel, Kevin M.; Aneja, Alka; Strunge, Leslie; Peebles, Jena; Fremont, Wanda P.; Stallone, Kimberly; AbdulSabur, Nuria; Higgins, Anne Marie; Shprintzen, Robert J.; Kates, Wendy R.

    2007-01-01

    The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria…

  17. Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome.

    PubMed

    Giardino, Giuliana; Cirillo, Emilia; Maio, Filomena; Gallo, Vera; Esposito, Tiziana; Naddei, Roberta; Grasso, Fiorentino; Pignata, Claudio

    2014-03-01

    OBJECTIVE. Enteropathy is a very common feature in patients with primary immunodeficiencies. In patients with Del22 gastrointestinal (GI) alterations, including feeding disorders and congenital abnormalities have been often reported, mostly in the first year of life. MATERIAL AND METHODS. Aim of this monocentric study is to better define the GI involvement in a cohort of 26 patients affected with Del22 syndrome. Anamnestic information was retrospectively collected for each patient. Weight and height parameters at the time of the screening were recorded. Plasma levels of hemoglobin, iron, ferritin, albumin, total protein, calcium, phosphorus, transaminase levels, antigliadin (AGA) IgA and IgG, and antitissue transglutaminase (anti-TGase) titers were measured. RESULTS. A GI involvement was identified in the 58% of patients. The prominent problems were abdominal pain, vomiting, gastroesophageal reflux and chronic constipation. Weight deficiency, short stature and failure to thrive were reported in 54, 42, and 30% of the patients, respectively. The evidence of sideropenic anemia, in keeping with hypoproteinemia, impaired acid steatocrit or cellobiose/mannitol test suggested an abnormal intestinal permeability. In this cohort, a high prevalence of AGA IgA and IgG positivity was observed. Celiac disease (CD) was suspected in three patients, and in one of them confirmed by histology. In this patient, a long-lasting gluten-free diet failed to restore the intestinal architecture. CONCLUSIONS. In conclusion, GI involvement is a very common feature in Del22 patients. A better characterization of GI involvement would be very useful to improve the management of these patients.

  18. How many breaks do we need to CATCH on 22q11?

    SciTech Connect

    Dallapiccola, B.; Pizzuti, A.; Novelli, G. ||

    1996-07-01

    The major clinical manifestations of DiGeorge syndrome (DGS; MIM 188400), which reflect developmental abnormalities of the 3d and 4th pharyngeal pouch derivatives, include thymus- and parathyroid-gland aplasia or hypoplasia and conotruncal cardiac malformations. The additional dysmorphic facial features, such as hypertelorism, cleft lip and palate, bifid uvula, and small/low-set ears, which are also common, presumably reflect the same defect. The DGS phenotype has been associated with chromosome abnormalities and, sometimes, is the effect of teratogenic agents such as retinoic acid and alcohol. 53 refs., 1 fig.

  19. Temporal Lobe Anatomy and Psychiatric Symptoms in Velocardiofacial Syndrome (22Q11.2 Deletion Syndrome)

    ERIC Educational Resources Information Center

    Kates, Wendy R.; Miller, Adam M.; Abdulsabur, Nuria; Antshel, Kevin M.; Conchelos, Jena; Fremont, Wanda; Roizen, Nancy

    2006-01-01

    Objective: To investigate the association between mesial temporal lobe morphology, ratios of prefrontal cortex to amygdala and hippocampus volumes, and psychiatric symptomatology in children and adolescents with velocardiofacial syndrome (VCFS). Method: Scores on behavioral rating scales and volumetric measures of the amygdala, hippocampus, and…

  20. Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

    ERIC Educational Resources Information Center

    Emanuel, Beverly S.

    2008-01-01

    Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

  1. Minute supernumerary ring chromosome 22 associated with cat eye syndrome: Further delineation of the critical region

    SciTech Connect

    Mears, A.J.; McDermid, H.E.; El-Shanti, H.

    1995-09-01

    Cat eye syndrome (CES) is typically associated with a supernumerary bisatellited marker chromosome (inv dup 22pter-22q11.2) resulting in four copies of this region. We describe an individual showing the inheritance of a minute supernumerary double ring chromosome 22, which resulted in expression of all cardinal features of CES. The size of the ring was determined by DNA dosage analysis and FISH analysis for five loci mapping to 22q11.2. The probes to the loci D22S9, D22S43, and ATP6E were present in four copies, whereas D22S57 and D22S181 were present in two copies. This finding further delineates the distal boundary of the critical region of CES, with ATP6E being the most distal duplicated locus identified. The phenotypically normal father and grandfather of the patient each had a small supernumerary ring chromosome and demonstrated three copies for the loci D22S9, D22S43, and ATP6E. Although three copies of this region have been reported in other cases with CES features, it is possible that the presence of four copies leads to greater susceptibility. 35 refs., 4 figs., 2 tabs.

  2. Long-range mapping and construction of a YAC contig within the cat eye syndrome critical region

    SciTech Connect

    Riazi, M.A.; Mears, A.J.; McDermid, H.E.

    1994-09-01

    Cat eye syndrome is characterized cytogenetically by the presence of a supernumerary marker chromosome derived from duplicated regions of 22pter-22q11.2. In order to study this syndrome, we have mapped and cloned within the CES critical region (CESCR) in 22q11.2. A long-range map was constructed using probes previously mapped to the CESCR by somatic cell hybrids. The map spans from probes LN63 to D22S36 and covers approximately 3 Mb. Probes within the region were used to isolate YACs, producing a contig of approximately 1.5 Mb (cLN63-D22S57). DNA studies of a cat eye patient with an unusual marker chromosome refined the minimal critical region proximal to D22S57, indicating that most of the CESCR is now cloned. The physical map will allow us to further delineate the CESCR and isolate genes in the region. Towards this end, we have performed {open_quotes}exon-trapping{close_quotes}on a cosmid, CN63, in this region. A 250 bp exon was isolated which maps to the CESCR and has no homology in GenBank. Further characterization of the gene containing this exon is in progress.

  3. Caregiver and Adult Patient Perspectives on the Importance of a Diagnosis of 22q11.2 Deletion Syndrome

    ERIC Educational Resources Information Center

    Costain, G.; Chow, E. W. C.; Ray, P. N.; Bassett, A. S.

    2012-01-01

    Background: Recent advances in genetics are particularly relevant in the field of intellectual disability (ID), where sub-microscopic deletions or duplications of genetic material are increasingly implicated as known or suspected causal factors. Data-driven reports on the impact of providing an aetiological explanation in ID are needed to help…

  4. DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects

    PubMed Central

    Gao, Wenming; Higaki, Takashi; Eguchi-Ishimae, Minenori; Iwabuki, Hidehiko; Wu, Zhouying; Yamamoto, Eiichi; Takata, Hidemi; Ohta, Masaaki; Imoto, Issei; Ishii, Eiichi; Eguchi, Mariko

    2015-01-01

    Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.2 region cannot be detected by fluorescence in situ hybridization (FISH), which is used to detect deletion in DGS. We investigated the presence of genomic aberrations in six patients with congenital conotruncal heart defects, who show no deletion at 22q11.2 in an initial screening by FISH. In these patients, no abnormalities were identified in the coding region of the TBX1 gene, one of the key genes responsible for the phenotype of DGS. However, when copy number alteration was analyzed by high-resolution array analysis, a small deletion or duplication in the proximal end of DiGeorge critical region was detected in two patients. The affected region contains the DGCR6 and PRODH genes. DGCR6 has been reported to affect the expression of the TBX1 gene. Our results suggest that altered dosage of gene(s) other than TBX1, possibly DGCR6, may also be responsible for the development of conotruncal heart defects observed in patients with DGS and, in particular, in those with stand-alone conotruncal heart defects. PMID:27081520

  5. An unbalanced 5;22 translocation in a patient with features of VCFS: Confirmation by FISH of loss of the DGS/VCFS critical region

    SciTech Connect

    Smith, J.J.; McGlothlin, J.C.; Lindsay, E.A.

    1994-09-01

    A 14-month-old male with a history of ventricular septal defect (VSD) and cleft lip and palate (CL/P) was referred for evaluation because of growth retardation, developmental delay and hypotonia. The initial cytogenetic analysis was 45,XY,-5,-22,+der(5)t(5q:22q). Determination of breakpoints 5q35.3 and 22q11.2 were made on G-banded chromosomes with band lengths of over 550. However, with both regions being light G bands, it was difficult to tell if the break in 22 was proximal to or distal to the DiGeorge syndrome/velocardiofacial syndrome (DGS/VCFS) critical region. Since the patient had a VSD and CL/P, velocardiofacial syndrome and a deletion of the DGS/VCFS critical region was suspected. FISH analysis of the derivative chromosome was performed with a cocktail containing two probes (ONCOR), D22S75, which maps to the DGS/VCFS region in 22q11.2 and D22S39, which maps to 22q13.3 and is used as a control for the presence of chromosome 22. Three fluorescent signals were observed, two on the normal 22 and the third on the terminal end of the derivative 5 chromosome verifying the translocation of 22q to 5q. No signal was observed for D22S75 on the proximal part of the translocated segment, verifying a deletion of the DGS/VCFS region in a patient whose clinical evaluation is consistent with velocardiofacial syndrome. Experiments with additional probes are underway to determine the deletion boundaries.

  6. Predicting reading comprehension academic achievement in late adolescents with velo-cardio-facial (22q11.2 deletion) syndrome (VCFS): A longitudinal study

    PubMed Central

    Antshel, Kevin M.; Hier, Bridget O.; Fremont, Wanda; Faraone, Stephen V.; Kates, Wendy R.

    2015-01-01

    Background The primary objective of the current study was to examine the childhood predictors of adolescent reading comprehension in velo-cardio-facial syndrome (VCFS). Although much research has focused on mathematics skills among individuals with VCFS, no studies have examined predictors of reading comprehension. Methods 69 late adolescents with VCFS , 23 siblings of youth with VCFS and 30 community controls participated in a longitudinal research project and had repeat neuropsychological test batteries and psychiatric evaluations every 3 years. The Wechsler Individual Achievement Test – 2nd edition (WIAT-II) Reading Comprehension subtest served as our primary outcome variable. Results Consistent with previous research, children and adolescents with VCFS had mean reading comprehension scores on the WIAT-II which were approximately two standard deviations below the mean and word reading scores approximately one standard deviation below the mean. A more novel finding is that relative to both control groups, individuals with VCFS demonstrated a longitudinal decline in reading comprehension abilities yet a slight increase in word reading abilities. In the combined control sample, WISC-III FSIQ, WIAT-II Word Reading, WISC-III Vocabulary and CVLT-C List A Trial 1 accounted for 75% of the variance in Time 3 WIAT-II Reading Comprehension scores. In the VCFS sample, WISC-III FSIQ, BASC-Teacher Aggression, CVLT-C Intrusions, Tower of London, Visual Span Backwards, WCST non-perseverative errors, WIAT-II Word Reading and WISC-III Freedom from Distractibility index accounted for 85% of the variance in Time 3 WIAT-II Reading Comprehension scores. A principal component analysis with promax rotation computed on the statistically significant Time 1 predictor variables in the VCFS sample resulted in three factors: Word reading decoding / Interference control, Self-Control / Self-Monitoring and Working Memory. Conclusions Childhood predictors of late adolescent reading comprehension in VCFS differ in some meaningful ways from predictors in the non-VCFS population. These results offer some guidance for how best to consider intervention efforts to improve reading comprehension in the VCFS population. PMID:24861691

  7. Velocardiofacial syndrome in father and daughter: What is the mechanism for the deletion 22(q11.2q11.2) in only the daughter?

    SciTech Connect

    Magenis, R.E.; Gunter, K.; Toth-Fejel, S.

    1994-09-01

    E.G. had marked feeding difficulty noted at birth; the cause was determined to be a paralyzed palate. In 1992 chromosome studies were performed because of the provisional diagnosis of velocardiofacial syndrome, and a small interstitial deletion of chromosome 22 was found. Recently the family was seen in our Genetics Clinic. The father had unusual facial features shared by his daughter, a paralyzed upper lip and a history of repaired Tetralogy of Fallot. His chromosomes appeared normal. FISH studies were performed on the child`s peripheral blood using the ONCOR DiGeorge region probe (D22S75) and the deletion verified. However, the father`s chromosomes were not deleted for the ONCOR probe (D22S75) and probe DO832 sent to us by Peter Scambler. Skin cells were then obtained and no deletion was detected in a total of 66 cells examined using both probes. Several questions arise from these data: does the father have velocardiofacial syndrome? Does he have occult mosaicism? Does he have a molecular deletion not detected by the probes used? And was this deletion somehow {open_quotes}amplified{close_quotes} in his daughter?

  8. Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep

    PubMed Central

    Funato, Hiromasa; Sato, Makito; Sinton, Christopher M.; Gautron, Laurent; Williams, S. Clay; Skach, Amber; Elmquist, Joel K.; Skoultchi, Arthur I.; Yanagisawa, Masashi

    2010-01-01

    Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoid-like (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain–hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although Gscl−/− mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl−/− mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl−/− mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results indicate that the absence of Gscl and Dgcr14 in the IP results in altered regulation of REM sleep. PMID:20921407

  9. Evidence for Involvement of GNB1L in Autism

    PubMed Central

    Chen, Ying-Zhang; Matsushita, Mark; Girirajan, Santhosh; Lisowski, Mark; Sun, Elizabeth; Sul, Youngmee; Bernier, Raphael; Estes, Annette; Dawson, Geraldine; Minshew, Nancy; Shellenberg, Gerard D; Eichler, Evan E; Rieder, Mark J; Nickerson, Deborah A; Tsuang, Debby W; Tsuang, Ming T; Wijsman, Ellen M; Raskind, Wendy H; Brkanac, Zoran

    2012-01-01

    Structural variations in the chromosome 22q11.2 region mediated by nonallelic homologous recombination result in 22q11.2 deletion (del22q11.2) and 22q11.2 duplication (dup22q11.2) syndromes. The majority of del22q11.2 cases have facial and cardiac malformations, immunologic impairments, specific cognitive profile and increased risk for schizophrenia and autism spectrum disorders (ASDs). The phenotype of dup22q11.2 is frequently without physical features but includes the spectrum of neurocognitive abnormalities. Although there is substantial evidence that haploinsufficiency for TBX1 plays a role in the physical features of del22q11.2, it is not known which gene(s) in the critical 1.5 Mb region are responsible for the observed spectrum of behavioral phenotypes. We identified an individual with a balanced translocation 46,XY,t(1;22)(p36.1;q11.2) and a behavioral phenotype characterized by cognitive impairment, autism, and schizophrenia in the absence of congenital malformations. Using somatic cell hybrids and comparative genomic hybridization (CGH) we mapped the chromosome-22 breakpoint within intron 7 of the GNB1L gene. Copy number evaluations and direct DNA sequencing of GNB1L in 271 schizophrenia and 513 autism cases revealed dup22q11.2 in two families with autism and private GNB1L missense variants in conserved residues in three families (P = 0.036). The identified missense variants affect residues in the WD40 repeat domains and are predicted to have deleterious effects on the protein. Prior studies provided evidence that GNB1L may have a role in schizophrenia. Our findings support involvement of GNB1L in ASDs as well. © 2011 Wiley Periodicals, Inc. PMID:22095694

  10. Thinking Critically about Critical Thinking

    ERIC Educational Resources Information Center

    Mulnix, Jennifer Wilson

    2012-01-01

    As a philosophy professor, one of my central goals is to teach students to think critically. However, one difficulty with determining whether critical thinking can be taught, or even measured, is that there is widespread disagreement over what critical thinking actually is. Here, I reflect on several conceptions of critical thinking, subjecting…

  11. Critical assumptions: thinking critically about critical thinking.

    PubMed

    Riddell, Thelma

    2007-03-01

    The concept of critical thinking has been featured in nursing literature for the past 20 years. It has been described but not defined by both the American Association of Colleges of Nursing and the National League for Nursing, although their corresponding accreditation bodies require that critical thinking be included in nursing curricula. In addition, there is no reliable or valid measurement tool for critical thinking ability in nursing. As a result, there is a lack of research support for the assumptions that critical thinking can be learned and that critical thinking ability improves clinical competence. Brookfield suggested that commitments should be made only after a period of critically reflective analysis, during which the congruence between perceptions and reality are examined. In an evidence-based practice profession, we, as nurse educators, need to ask ourselves how we can defend our assumptions that critical thinking can be learned and that critical thinking improves the quality of nursing practice, especially when there is virtually no consensus on a definition.

  12. Critical Care

    MedlinePlus

    Critical care helps people with life-threatening injuries and illnesses. It might treat problems such as complications from surgery, ... attention by a team of specially-trained health care providers. Critical care usually takes place in an ...

  13. Archetypal Criticism.

    ERIC Educational Resources Information Center

    Chesebro, James W.; And Others

    1990-01-01

    Argues that archetypal criticism is a useful way of examining universal, historical, and cross-cultural symbols in classrooms. Identifies essential features of an archetype; outlines operational and critical procedures; illustrates archetypal criticism as applied to the cross as a symbol; and provides a synoptic placement for archetypal criticism…

  14. Critical Thinking vs. Critical Consciousness

    ERIC Educational Resources Information Center

    Doughty, Howard A.

    2006-01-01

    This article explores four kinds of critical thinking. The first is found in Socratic dialogues, which employ critical thinking mainly to reveal logical fallacies in common opinions, thus cleansing superior minds of error and leaving philosophers free to contemplate universal verities. The second is critical interpretation (hermeneutics) which…

  15. Critically Thinking about Critical Thinking

    ERIC Educational Resources Information Center

    Weissberg, Robert

    2013-01-01

    In this article, the author states that "critical thinking" has mesmerized academics across the political spectrum and that even high school students are now being called upon to "think critically." He furthers adds that it is no exaggeration to say that "critical thinking" has quickly evolved into a scholarly…

  16. How Critical Is Critical Thinking?

    ERIC Educational Resources Information Center

    Shaw, Ryan D.

    2014-01-01

    Recent educational discourse is full of references to the value of critical thinking as a 21st-century skill. In music education, critical thinking has been discussed in relation to problem solving and music listening, and some researchers suggest that training in critical thinking can improve students' responses to music. But what exactly is…

  17. Criticality Model

    SciTech Connect

    A. Alsaed

    2004-09-14

    The ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2003) presents the methodology for evaluating potential criticality situations in the monitored geologic repository. As stated in the referenced Topical Report, the detailed methodology for performing the disposal criticality analyses will be documented in model reports. Many of the models developed in support of the Topical Report differ from the definition of models as given in the Office of Civilian Radioactive Waste Management procedure AP-SIII.10Q, ''Models'', in that they are procedural, rather than mathematical. These model reports document the detailed methodology necessary to implement the approach presented in the Disposal Criticality Analysis Methodology Topical Report and provide calculations utilizing the methodology. Thus, the governing procedure for this type of report is AP-3.12Q, ''Design Calculations and Analyses''. The ''Criticality Model'' is of this latter type, providing a process evaluating the criticality potential of in-package and external configurations. The purpose of this analysis is to layout the process for calculating the criticality potential for various in-package and external configurations and to calculate lower-bound tolerance limit (LBTL) values and determine range of applicability (ROA) parameters. The LBTL calculations and the ROA determinations are performed using selected benchmark experiments that are applicable to various waste forms and various in-package and external configurations. The waste forms considered in this calculation are pressurized water reactor (PWR), boiling water reactor (BWR), Fast Flux Test Facility (FFTF), Training Research Isotope General Atomic (TRIGA), Enrico Fermi, Shippingport pressurized water reactor, Shippingport light water breeder reactor (LWBR), N-Reactor, Melt and Dilute, and Fort Saint Vrain Reactor spent nuclear fuel (SNF). The scope of this analysis is to document the criticality computational method. The criticality

  18. Critical Muralism

    ERIC Educational Resources Information Center

    Rosette, Arturo

    2009-01-01

    This study focuses on the development and practices of Critical Muralists--community-educator-artist-leader-activists--and situates these specifically in relation to the Mexican mural tradition of los Tres Grandes and in relation to the history of public art more generally. The study examines how Critical Muralists address artistic and…

  19. Critics and Criticism of Education

    ERIC Educational Resources Information Center

    Ornstein, Allan C.

    1977-01-01

    Radical educational critics, such as Edgar Friedenberg, Paul Goodman, A. S. Neill, John Holt, Jonathan Kozol, Herbert Kohl, James Herndon, and Ivan Illich, have few constructive goals, no strategy for broad change, and a disdain for modernization and compromise. Additionally, these critics, says the author, fail to consider social factors related…

  20. Staying Critical

    ERIC Educational Resources Information Center

    Carr, Wilfred; Kemmis, Stephen

    2005-01-01

    In this article, the two authors of "Becoming Critical: education, knowledge and action research" look back at the book's history since its publication 20 years ago. We describe how the book was originally written, and the diverse responses and reactions that it has produced. We identify some of the book's inadequacies and limitations, and…

  1. Critical Information at Critical Moments

    ERIC Educational Resources Information Center

    Fierman, Ben; Thrower, Raymond H., Jr.

    2011-01-01

    On a daily basis, administrators are reminded of the potential, perhaps the likelihood, of violence or natural crises on their campuses. Comprehensive studies have been conducted and point to recommendations and best practices for planning, preparing, responding to, and recovering from critical incidents. The International Association of Campus…

  2. Critical Pedagogy for Critical Mathematics Education

    ERIC Educational Resources Information Center

    Tutak, Fatma Aslan; Bondy, Elizabeth; Adams, Thomasenia L.

    2011-01-01

    This article provides a brief introduction to critical pedagogy and further discussion on critical mathematics education. Critical mathematics education enables students to read the world with mathematics. Three emerging domains of mathematics education related to critical mathematics education are discussed in this manuscript: ethnomathematics,…

  3. Critical Viewing: Stimulant to Critical Thinking.

    ERIC Educational Resources Information Center

    O'Reilly, Kevin; Splaine, John

    This document is intended to improve the critical viewing skills and increase the understanding and appreciation of what is viewed. Included are the chapters: (1) "Critical Thinking: The Parts of an Argument," intended to develop a process to help a person judge arguments in what is read, seen, and heard; (2) "Critical Viewing: Concepts, Skills,…

  4. Critical Thinking in Adulthood.

    ERIC Educational Resources Information Center

    Fulton, Rodney D.

    Critical thinking is often defined as that which a particular instrument measures. The most prominent tests are the Watson-Glaser Critical Thinking Appraisal, the Ennis-Weir Critical Thinking Essay Test, and the Cornell Critical Thinking Tests. Watson and Glaser's (1980) view of critical thinking is "a composite of attitudes, knowledge, and…

  5. Critical Care in Critical Access Hospitals.

    PubMed

    Seright, Teresa J; Winters, Charlene A

    2015-10-01

    What began as a grant-funded demonstration project, as a means of bridging the gap in rural health care, has developed into a critical access hospital system comprising 1328 facilities across 45 states. A critical access hospital is not just a safety net for health care in a rural community. Such hospitals may also provide specialized services such as same-day surgery, infusion therapy, and intensive care. For hospitals located near the required minimum of 35 miles from a tertiary care center, management of critically ill patients may be a matter of stabilization and transfer. Critical access hospitals in more rural areas are often much farther from tertiary care; some of these hospitals are situated within frontier areas of the United States. This article describes the development of critical access hospitals, provision of care and services, challenges to critical care in critical access hospitals, and suggestions to address gaps in research and collaborative care.

  6. Critical Materials Institute

    ScienceCinema

    Alex King

    2016-07-12

    Ames Laboratory Director Alex King talks about the goals of the Critical Materials Institute in diversifying the supply of critical materials, developing substitute materials, developing tools and techniques for recycling critical materials, and forecasting materials needs to avoid future shortages.

  7. Critical Materials Institute

    SciTech Connect

    Alex King

    2013-01-09

    Ames Laboratory Director Alex King talks about the goals of the Critical Materials Institute in diversifying the supply of critical materials, developing substitute materials, developing tools and techniques for recycling critical materials, and forecasting materials needs to avoid future shortages.

  8. Critical Care Team

    MedlinePlus

    ... Please enable scripts and reload this page. About Critical Care Currently selected Team Questions During the ICU Chronic ... Team Currently selected Questions Patients and Families > About Critical Care > Team Tweet Team Page Content ​The critical care ...

  9. A Critical Humanist Curriculum

    ERIC Educational Resources Information Center

    Magill, Kevin; Rodriguez, Arturo

    2015-01-01

    This essay is a critical humanist discussion of curriculum; a departure from the technicist view of education [education meant to support a global capitalist economy] and an analysis of curriculum considering critical humanism, political economy and critical race theory among other modes of critical analysis and inquiry. Our discussion supports a…

  10. Critical Approaches to Critical Pedagogy in Greece

    ERIC Educational Resources Information Center

    Grollios, George; Liambas, Anastassios

    2015-01-01

    This paper is an initial review of the presentations and uses of critical pedagogy in Greek educational literature since the mid-1980s. These have appeared in the form of three books and an edited volume (translated in Greek), all written by American critical educators, as well as in texts produced by Greek educators who have either written the…

  11. A Critical Look into Critical Pedagogy

    ERIC Educational Resources Information Center

    Pishghadam, Reza; Meidani, Elham Naji

    2012-01-01

    In line with postmodern philosophy, critical pedagogy has gained considerable importance and has become a valuable educational goal. The purpose of this study is to dig into the effects of critical pedagogy in a modernist educational system. To this aim, 15 Iranian university students were asked to write down their feelings at the end of a course…

  12. Revalorizing the Critical Attitude for Critical Education

    ERIC Educational Resources Information Center

    Amsler, Sarah S.

    2011-01-01

    This article argues that at a moment of crisis in education, the defence of critical pedagogy is vitally important. However, it also suggests that such a defence should be more than a "cri de coeur" that asserts principles and methods of criticality against those of neoliberal or conservative education policy. Narratives of a totalising "crisis of…

  13. How critical is chronic critical leg ischaemia?

    PubMed

    Kroese, A J; Stranden, E

    1998-01-01

    "Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added. PMID:9676324

  14. How critical is chronic critical leg ischaemia?

    PubMed

    Kroese, A J; Stranden, E

    1998-01-01

    "Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added.

  15. Anomalous critical fields in quantum critical superconductors.

    PubMed

    Putzke, C; Walmsley, P; Fletcher, J D; Malone, L; Vignolles, D; Proust, C; Badoux, S; See, P; Beere, H E; Ritchie, D A; Kasahara, S; Mizukami, Y; Shibauchi, T; Matsuda, Y; Carrington, A

    2014-01-01

    Fluctuations around an antiferromagnetic quantum critical point (QCP) are believed to lead to unconventional superconductivity and in some cases to high-temperature superconductivity. However, the exact mechanism by which this occurs remains poorly understood. The iron-pnictide superconductor BaFe2(As(1-x)P(x))2 is perhaps the clearest example to date of a high-temperature quantum critical superconductor, and so it is a particularly suitable system to study how the quantum critical fluctuations affect the superconducting state. Here we show that the proximity of the QCP yields unexpected anomalies in the superconducting critical fields. We find that both the lower and upper critical fields do not follow the behaviour, predicted by conventional theory, resulting from the observed mass enhancement near the QCP. Our results imply that the energy of superconducting vortices is enhanced, possibly due to a microscopic mixing of antiferromagnetism and superconductivity, suggesting that a highly unusual vortex state is realized in quantum critical superconductors. PMID:25477044

  16. Anomalous critical fields in quantum critical superconductors

    PubMed Central

    Putzke, C.; Walmsley, P.; Fletcher, J. D.; Malone, L.; Vignolles, D.; Proust, C.; Badoux, S.; See, P.; Beere, H. E.; Ritchie, D. A.; Kasahara, S.; Mizukami, Y.; Shibauchi, T.; Matsuda, Y.; Carrington, A.

    2014-01-01

    Fluctuations around an antiferromagnetic quantum critical point (QCP) are believed to lead to unconventional superconductivity and in some cases to high-temperature superconductivity. However, the exact mechanism by which this occurs remains poorly understood. The iron-pnictide superconductor BaFe2(As1−xPx)2 is perhaps the clearest example to date of a high-temperature quantum critical superconductor, and so it is a particularly suitable system to study how the quantum critical fluctuations affect the superconducting state. Here we show that the proximity of the QCP yields unexpected anomalies in the superconducting critical fields. We find that both the lower and upper critical fields do not follow the behaviour, predicted by conventional theory, resulting from the observed mass enhancement near the QCP. Our results imply that the energy of superconducting vortices is enhanced, possibly due to a microscopic mixing of antiferromagnetism and superconductivity, suggesting that a highly unusual vortex state is realized in quantum critical superconductors. PMID:25477044

  17. Toward critical bioethics.

    PubMed

    Árnason, Vilhjálmur

    2015-04-01

    This article deals with the question as to what makes bioethics a critical discipline. It considers different senses of criticism and evaluates their strengths and weaknesses. A primary method in bioethics as a philosophical discipline is critical thinking, which implies critical evaluation of concepts, positions, and arguments. It is argued that the type of analytical criticism that restricts its critical role to critical thinking of this type often suffers from other intellectual flaws. Three examples are taken to demonstrate this: premature criticism, uncritical self-understanding of theoretical assumptions, and narrow framing of bioethical issues. Such flaws can lead both to unfair treatment of authors and to uncritical discussion of topics. In this context, the article makes use of Häyry's analysis of different rationalities in bioethical approaches and argues for the need to recognize the importance of communicative rationality for critical bioethics. A radically different critical approach in bioethics, rooted in social theory, focuses on analyses of power relations neglected in mainstream critical thinking. It is argued that, although this kind of criticism provides an important alternative in bioethics, it suffers from other shortcomings that are rooted in a lack of normative dimensions. In order to complement these approaches and counter their shortcomings, there is a need for a bioethics enlightened by critical hermeneutics. Such hermeneutic bioethics is aware of its own assumptions, places the issues in a wide context, and reflects critically on the power relations that stand in the way of understanding them. Moreover, such an approach is dialogical, which provides both a critical exercise of speech and a normative dimension implied in the free exchange of reasons and arguments. This discussion is framed by Hedgecoe's argument that critical bioethics needs four elements: to be empirically rooted, theory challenging, reflexive, and politely skeptical.

  18. Toward critical bioethics.

    PubMed

    Árnason, Vilhjálmur

    2015-04-01

    This article deals with the question as to what makes bioethics a critical discipline. It considers different senses of criticism and evaluates their strengths and weaknesses. A primary method in bioethics as a philosophical discipline is critical thinking, which implies critical evaluation of concepts, positions, and arguments. It is argued that the type of analytical criticism that restricts its critical role to critical thinking of this type often suffers from other intellectual flaws. Three examples are taken to demonstrate this: premature criticism, uncritical self-understanding of theoretical assumptions, and narrow framing of bioethical issues. Such flaws can lead both to unfair treatment of authors and to uncritical discussion of topics. In this context, the article makes use of Häyry's analysis of different rationalities in bioethical approaches and argues for the need to recognize the importance of communicative rationality for critical bioethics. A radically different critical approach in bioethics, rooted in social theory, focuses on analyses of power relations neglected in mainstream critical thinking. It is argued that, although this kind of criticism provides an important alternative in bioethics, it suffers from other shortcomings that are rooted in a lack of normative dimensions. In order to complement these approaches and counter their shortcomings, there is a need for a bioethics enlightened by critical hermeneutics. Such hermeneutic bioethics is aware of its own assumptions, places the issues in a wide context, and reflects critically on the power relations that stand in the way of understanding them. Moreover, such an approach is dialogical, which provides both a critical exercise of speech and a normative dimension implied in the free exchange of reasons and arguments. This discussion is framed by Hedgecoe's argument that critical bioethics needs four elements: to be empirically rooted, theory challenging, reflexive, and politely skeptical

  19. Foundations for Critical Thinking

    ERIC Educational Resources Information Center

    Bers, Trudy; Chun, Marc; Daly, William T.; Harrington, Christine; Tobolowsky, Barbara F.

    2015-01-01

    "Foundations for Critical Thinking" explores the landscape of critical-thinking skill development and pedagogy through foundational chapters and institutional case studies involving a range of students in diverse settings. By establishing a link between active learning and improved critical thinking, this resource encourages all higher…

  20. Reimagining Critical Theory

    ERIC Educational Resources Information Center

    Rexhepi, Jevdet; Torres, Carlos Alberto

    2011-01-01

    This paper discusses Critical Theory, a model of theorizing in the field of the political sociology of education. We argue for a "reimagined" Critical Theory to herald an empowering, liberatory education that fosters curiosity and critical thinking, and a means for successful bottom-up, top-down political engagement. We present arguments at a…

  1. Teaching Critical Reflection

    ERIC Educational Resources Information Center

    Smith, Elizabeth

    2011-01-01

    Despite long-standing commitment to the notion of critical reflection across the healthcare professions it is unusual for critical theory and practice to be taught as explicit subjects in healthcare higher education. There is evidence to show that reflective techniques such as critical portfolios and reflective diaries can help students to…

  2. Reconceptualising Critical Digital Literacy

    ERIC Educational Resources Information Center

    Pangrazio, Luciana

    2016-01-01

    While it has proved a useful concept during the past 20 years, the notion of "critical digital literacy" requires rethinking in light of the fast-changing nature of young people's digital practices. This paper contrasts long-established notions of "critical digital literacy" (based primarily around the critical consumption of…

  3. Defining critical thoughts.

    PubMed

    Lovatt, Abbie

    2014-05-01

    Nursing education has long struggled to define critical thinking and explain how the process of critical thinking fits into the context of nursing. Despite this long time struggle, nurses and nurse educators continue to strive to foster critical thinking skills in nursing students as intuitively most nurses believe that critical thinking is necessary to function competently in the workplace. This article explores the most recent work of Dr. Stephen Brookfield and ties the concepts which are explored in Brookfield's work to nursing practice. Brookfield identifies that learners understand the meaning of critical thinking the best when the process is first demonstrated. Role modeling is a method educators can use to demonstrate critical thinking and is a strategy which nurses often use in the clinical area to train and mentor new nursing staff. Although it is not a new strategy in nursing education, it is a valuable strategy to engage learners in critical thinking activities. PMID:24418065

  4. Critical fluid light scattering

    NASA Technical Reports Server (NTRS)

    Gammon, Robert W.

    1988-01-01

    The objective is to measure the decay rates of critical density fluctuations in a simple fluid (xenon) very near its liquid-vapor critical point using laser light scattering and photon correlation spectroscopy. Such experiments were severely limited on Earth by the presence of gravity which causes large density gradients in the sample when the compressibility diverges approaching the critical point. The goal is to measure fluctuation decay rates at least two decades closer to the critical point than is possible on earth, with a resolution of 3 microK. This will require loading the sample to 0.1 percent of the critical density and taking data as close as 100 microK to the critical temperature. The minimum mission time of 100 hours will allow a complete range of temperature points to be covered, limited by the thermal response of the sample. Other technical problems have to be addressed such as multiple scattering and the effect of wetting layers. The experiment entails measurement of the scattering intensity fluctuation decay rate at two angles for each temperature and simultaneously recording the scattering intensities and sample turbidity (from the transmission). The analyzed intensity and turbidity data gives the correlation length at each temperature and locates the critical temperature. The fluctuation decay rate data from these measurements will provide a severe test of the generalized hydrodynamic theories of transport coefficients in the critical regions. When compared to equivalent data from binary liquid critical mixtures they will test the universality of critical dynamics.

  5. Critical Psychologies for Critical Health Literacies

    ERIC Educational Resources Information Center

    Corcoran, Tim

    2014-01-01

    Health education is largely informed by psychological theories and practices that pursue reductionist views of people learning. However, critical attention is moving to understand health in ways that reconsider relationships to context and the forms of life within which everyday living takes place. This shift is apparent in theoretical…

  6. Criticality Model Report

    SciTech Connect

    J.M. Scaglione

    2003-03-12

    The purpose of the ''Criticality Model Report'' is to validate the MCNP (CRWMS M&O 1998h) code's ability to accurately predict the effective neutron multiplication factor (k{sub eff}) for a range of conditions spanned by various critical configurations representative of the potential configurations commercial reactor assemblies stored in a waste package may take. Results of this work are an indication of the accuracy of MCNP for calculating eigenvalues, which will be used as input for criticality analyses for spent nuclear fuel (SNF) storage at the proposed Monitored Geologic Repository. The scope of this report is to document the development and validation of the criticality model. The scope of the criticality model is only applicable to commercial pressurized water reactor fuel. Valid ranges are established as part of the validation of the criticality model. This model activity follows the description in BSC (2002a).

  7. Vulnerability of critical infrastructures : identifying critical nodes.

    SciTech Connect

    Cox, Roger Gary; Robinson, David Gerald

    2004-06-01

    The objective of this research was the development of tools and techniques for the identification of critical nodes within critical infrastructures. These are nodes that, if disrupted through natural events or terrorist action, would cause the most widespread, immediate damage. This research focuses on one particular element of the national infrastructure: the bulk power system. Through the identification of critical elements and the quantification of the consequences of their failure, site-specific vulnerability analyses can be focused at those locations where additional security measures could be effectively implemented. In particular, with appropriate sizing and placement within the grid, distributed generation in the form of regional power parks may reduce or even prevent the impact of widespread network power outages. Even without additional security measures, increased awareness of sensitive power grid locations can provide a basis for more effective national, state and local emergency planning. A number of methods for identifying critical nodes were investigated: small-world (or network theory), polyhedral dynamics, and an artificial intelligence-based search method - particle swarm optimization. PSO was found to be the only viable approach and was applied to a variety of industry accepted test networks to validate the ability of the approach to identify sets of critical nodes. The approach was coded in a software package called Buzzard and integrated with a traditional power flow code. A number of industry accepted test networks were employed to validate the approach. The techniques (and software) are not unique to power grid network, but could be applied to a variety of complex, interacting infrastructures.

  8. Critical Viscosity of Xenon

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Because xenon near the critical point will collapse under its own weight, experiments on Earth (green line) are limited as they get closer (toward the left) to the critical point. CVX in the microgravity of space (red line) moved into unmeasured territory that scientists had not been able to reach.

  9. The Need for Critics.

    ERIC Educational Resources Information Center

    Purves, Alan C.

    1994-01-01

    Responds to an article in the same issue of this journal about educational criticism as a form of qualitative inquiry. Argues that research in education has become a dead end. Agrees in the main with the article, but finds its view of criticism somewhat limited. Discusses the classroom itself as hypertext. (SR)

  10. Critical Thinking in Math.

    ERIC Educational Resources Information Center

    Ronis, Diane

    This booklet includes a wheel of problem solving strategies and a seven-step process for approaching and solving complicated problems. The information provided gives students a variety of ways to approach, analyze, and think critically about mathematics problems. The chapters present guides to promoting critical thinking in cooperative groups…

  11. Critical Literacy: Foundational Notes

    ERIC Educational Resources Information Center

    Luke, Allan

    2012-01-01

    The term "critical literacy" refers to use of the technologies of print and other media of communication to analyze, critique, and transform the norms, rule systems, and practices governing the social fields of everyday life (A. Luke, 2004). Since Freire's (1970) educational projects in Brazil, approaches to critical literacy have been developed…

  12. Against Critical Thinking Pedagogy

    ERIC Educational Resources Information Center

    Hayes, David

    2015-01-01

    Critical thinking pedagogy is misguided. Ostensibly a cure for narrowness of thought, by using the emotions appropriate to conflict, it names only one mode of relation to material among many others. Ostensibly a cure for fallacies, critical thinking tends to dishonesty in practice because it habitually leaps to premature ideas of what the object…

  13. Rethinking Critical Thinking

    ERIC Educational Resources Information Center

    Downs, Christopher J.

    2008-01-01

    Critical thinking is of primary importance in higher education, yet the concept remains slippery and the skill elusive. The author argues that most current critical thinking textbooks are out of line with the seminal work of John Dewey. Rather than logical argument and justification, it is suggested that carefulness, open-mindedness and creativity…

  14. Critical Chain Exercises

    ERIC Educational Resources Information Center

    Doyle, John Kevin

    2010-01-01

    Critical Chains project management focuses on holding buffers at the project level vs. task level, and managing buffers as a project resource. A number of studies have shown that Critical Chain project management can significantly improve organizational schedule fidelity (i.e., improve the proportion of projects delivered on time) and reduce…

  15. Critical Teaching and Learning.

    ERIC Educational Resources Information Center

    Young, R. E.

    1988-01-01

    This essay begins with a description of Jurgen Habermas's theory of communicative action, emphasizing aspects which relate to a critical theory of teaching/learning. Existing theory and research is reviewed. A critical theory of pedagogy as a form of communicative action or interaction is presented. (MT)

  16. Critical Education Studies

    ERIC Educational Resources Information Center

    Boxley, Simon

    2015-01-01

    Education Studies as an academic discipline within HE in the UK is a contested area. One thing most Education Studies programmes might agree on is that they are "critical". But what is a genuinely critical Education Studies degree? And, how could such a programme survive within the hostile neoliberal environment of the contemporary UK?…

  17. Critical Social Numeracy.

    ERIC Educational Resources Information Center

    Lake, David

    2002-01-01

    Presents a five-step method to develop the critical numeracy knowledge of numerically intimidated students. Examines the method in detail, discussing Piagetian diagnostic tools and how to adapt the Structure of the Observed Learning Outcome (SOLO) taxonomy to teach critical numeracy. (CMK)

  18. CRITICAL LOADS METHODS

    EPA Science Inventory

    I summarize the results of an interagency project that 1) defines a generic approach to quantifying and reporting critical loads, and 2) exercises that generic approach by examining a data rich system -- the critical loads of sulfur deposition and it's effect on the chronic acidi...

  19. Creating a Critical Thinker

    ERIC Educational Resources Information Center

    Piergiovanni, Polly R.

    2014-01-01

    A college education is expected to improve students' critical thinking skills. Keeping students active in class--through writing activities and class discussion--has been shown to help students think critically. In this article, creative hands-on activities, which are common in engineering courses, are shown to improve students' critical…

  20. Critical Schwinger Pair Production.

    PubMed

    Gies, Holger; Torgrimsson, Greger

    2016-03-01

    We investigate Schwinger pair production in spatially inhomogeneous electric backgrounds. A critical point for the onset of pair production can be approached by fields that marginally provide sufficient electrostatic energy for an off-shell long-range electron-positron fluctuation to become a real pair. Close to this critical point, we observe features of universality which are analogous to continuous phase transitions in critical phenomena with the pair-production rate serving as an order parameter: electric backgrounds can be subdivided into universality classes and the onset of pair production exhibits characteristic scaling laws. An appropriate design of the electric background field can interpolate between power-law scaling, essential Berezinskii-Kosterlitz-Thouless-type scaling, and a power-law scaling with log corrections. The corresponding critical exponents only depend on the large-scale features of the electric background, whereas the microscopic details of the background play the role of irrelevant perturbations not affecting criticality. PMID:26991162

  1. Telemedicine in Critical Care

    PubMed Central

    Murias, Gastón; Sales, Bernat; Garcia-Esquirol, Oscar; Blanch, Lluis

    2009-01-01

    Critical care medicine is the specialty that cares for patients with acute life-threatening illnesses where intensivists look after all aspects of patient care. Nevertheless, shortage of physicians and nurses, the relationship between high costs and economic restrictions, and the fact that critical care knowledge is only available at big hospitals puts the system on the edge. In this scenario, telemedicine might provide solutions to improve availability of critical care knowledge where the patient is located, improve relationship between attendants in different institutions and education material for future specialist training. Current information technologies and networking capabilities should be exploited to improve intensivist coverage, advanced alarm systems and to have large critical care databases of critical care signals. PMID:19452034

  2. Higher Education: A Critical Business.

    ERIC Educational Resources Information Center

    Barnett, Ronald

    Current concepts of critical thinking need to be reconstrued into the much broader concept of "critical being" and applied to higher education. Under this construct, critical persons (students) become more than just critical thinkers; they engage critically with the world and with themselves; they not only reflect critically on knowledge, but also…

  3. A holographic critical point

    SciTech Connect

    DeWolfe, Oliver; Rosen, Christopher; Gubser, Steven S.

    2011-04-15

    We numerically construct a family of five-dimensional black holes exhibiting a line of first-order phase transitions terminating at a critical point at finite chemical potential and temperature. These black holes are constructed so that the equation of state and baryon susceptibilities approximately match QCD lattice data at vanishing chemical potential. The critical end point in the particular model we consider has temperature 143 MeV and chemical potential 783 MeV. Critical exponents are calculated, with results that are consistent with mean-field scaling relations.

  4. Greening critical care

    PubMed Central

    2011-01-01

    Climate change and environmental stewardship are phrases that have been defining the past few decades and promoting change in our societies. The sensitivities of intensive care as a specialty make the process of greening an intensive care unit a challenge, but not one that is insurmountable. This paper discusses opportunities for critical care to reduce its environmental impact and provide a framework change. The article includes suggestions of what can be done as an individual, as a unit and as a hospital. Generally, practices in critical care are accepted without questioning the environmental consequences. We believe it is time for change, and critical care should give environmental stewardship a higher priority. PMID:21635700

  5. Mission Critical Networking

    SciTech Connect

    Eltoweissy, Mohamed Y.; Du, David H.C.; Gerla, Mario; Giordano, Silvia; Gouda, Mohamed; Schulzrinne, Henning; Youssef, Moustafa

    2010-06-01

    Mission-Critical Networking (MCN) refers to networking for application domains where life or livelihood may be at risk. Typical application domains for MCN include critical infrastructure protection and operation, emergency and crisis intervention, healthcare services, and military operations. Such networking is essential for safety, security and economic vitality in our complex world characterized by uncertainty, heterogeneity, emergent behaviors, and the need for reliable and timely response. MCN comprise networking technology, infrastructures and services that may alleviate the risk and directly enable and enhance connectivity for mission-critical information exchange among diverse, widely dispersed, mobile users.

  6. Critical-point nuclei

    SciTech Connect

    Clark, R.M.

    2004-10-01

    It has been suggested that a change of nuclear shape may be described in terms of a phase transition and that specific nuclei may lie close to the critical point of the transition. Analytical descriptions of such critical-point nuclei have been introduced recently and they are described briefly. The results of extensive searches for possible examples of critical-point behavior are presented. Alternative pictures, such as describing bands in the candidate nuclei using simple {Delta}K = 0 and {Delta}K = 2 rotational-coupling models, are discussed, and the limitations of the different approaches highlighted. A possible critical-point description of the transition from a vibrational to rotational pairing phase is suggested.

  7. The Critical Thinking Workout.

    ERIC Educational Resources Information Center

    Masters, Terry McDaniel

    1991-01-01

    Presents a critical thinking exercise program, modeled on a physical exercise workout, for elementary teachers to use in the classroom. It includes warm-up exercises, a more strenuous workout, and a cool-down period for the brain. (SM)

  8. Critical Access Hospitals (CAH)

    MedlinePlus

    ... CAH Conditions of Participation . What are the location requirements for CAH status? Critical Access Hospitals must be ... clinic that does not meet the CAH distance requirements? As of January 1, 2008, all CAHs, including ...

  9. Critical chemotactic collapse

    NASA Astrophysics Data System (ADS)

    Lushnikov, Pavel M.

    2010-04-01

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schrödinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  10. Quantum Critical Elasticity.

    PubMed

    Zacharias, Mario; Paul, Indranil; Garst, Markus

    2015-07-10

    We discuss elastic instabilities of the atomic crystal lattice at zero temperature. Because of long-range shear forces of the solid, at such transitions the phonon velocities vanish, if at all, only along certain crystallographic directions, and, consequently, the critical phonon fluctuations are suppressed to a lower dimensional manifold and governed by a Gaussian fixed point. In the case of symmetry-breaking elastic transitions, a characteristic critical phonon thermodynamics arises that is found, e.g., to violate Debye's T(3) law for the specific heat. We point out that quantum critical elasticity is triggered whenever a critical soft mode couples linearly to the strain tensor. In particular, this is relevant for the electronic Ising-nematic quantum phase transition in a tetragonal crystal as discussed in the context of certain cuprates, ruthenates, and iron-based superconductors. PMID:26207483

  11. About Critical Care Nursing

    MedlinePlus

    ... Join Now Our Community Value of Belonging Member Benefits and Savings Awards Certification Apply Online Renew Your ... and traveling critical care nurses to fill staffing gaps in every part of the U.S. These requests ...

  12. Critical Viscosity of Xenon

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Shear thirning will cause a normally viscous fluid -- such as pie filling or whipped cream -- to deform and flow more readily under high shear conditions. In shear thinning, a pocket of fluid will deform and move one edge forward, as depicted here.

  13. Critical experiment data archiving

    SciTech Connect

    Koponen, B.L. ); Clayton, E.D.; Doherty, A.L. )

    1991-01-01

    Critical experiment facilities produced a large number of important data during the past 45 years; however, many useful data remain unpublished. The unpublished material exists in the form of experimenters' logbooks, notes, photographs, material descriptions, etc., This data could be important for computer code validation, understanding the physics of criticality, facility design, or for setting process limits. In the past, criticality specialists have been able to obtain unpublished details by direct contact with the experimenters. Obviously, this will not be possible indefinitely. Most of the US critical experiment facilities are now closed, and the experimenters are moving to other jobs, retiring, or otherwise becoming unavailable for this informal assistance. Also, the records are in danger of being discarded or lost during facility closures, cleanup activities, or in storage. A project was begun in 1989 to ensure that important unpublished data from critical experiment facilities in the United States are archived and made available as a resource of the US Department of Energy's (DOE's) Nuclear Criticality Information System (NCIS). The objective of this paper is to summarize the project accomplishments to date and bring these activities to the attention of those who might be aware of the location of source information needed for archiving and could assist in getting the materials included in the archive.

  14. Mapping Self-Organized Criticality onto Criticality

    NASA Astrophysics Data System (ADS)

    Sornette, Didier; Johansen, Anders; Dornic, Ivan

    1995-03-01

    We present a general conceptual framework for self-organized criticality (SOC), based on the recognition that it is nothing but the expression, “unfolded" in a suitable parameter space, of an underlying unstable dynamical critical point. More precisely, SOC is shown to result from the tunning of the order parameter to a vanishingly small, but positive value, thus ensuring that the corresponding control parameter lies exactly at its critical value for the underlying transition. This clarifies the role and nature of the very slow driving rate common to all systems exhibiting SOC. This mechanism is shown to apply to models of sandpiles, earthquakes, depinning, fractal growth and forest fires, which have been proposed as examples of SOC. Nous proposons une stratégie générale pour identifier le mécanisme responsable des phénomènes critiques auto-organisés, basée, sur l'idée qu'ils sont simplement la traduction, dans un espace de paramètres choisis, d'un point critique dynamique instable standard. La criticalité auto-organisée résulte du contrôle du paramètre d'ordre ajusté à une valeur positive tendant vers zéro, ce qui assure automatiquement que le paramètre de contrôle correspondant se cale exactement sur sa valeur critique de la transition de critique sous-jacente. Ce résultat explique le rôle particulier joué par le forçage infiniment lent qui est un caractère commun à tous les systèmes critiques auto-organisés. Nous appliquons ces idées aux modèles de tas de sable, aux modèles de tremblements de terre, de feux de forêts, aux transitions de décrochage et aux modèles de croissance fractale, qui ont été proposés comme autant d'exemples caractéristiques de la criticalité auto-organisée.

  15. Erik Erikson: critical times, critical theory.

    PubMed

    Douvan, E

    1997-01-01

    The work and legacy of Erik Erikson are described in this brief outline of his career, his theories, and his impact on psychoanalysis, psychology, history, and the broader culture. His conception of the adolescent task-weaving internal tastes, talents, and values together with elements of one's life history and the demands of one's culture into a coherent identity-has had profound effects on developmental psychology and the way in which sophisticated youth construct and describe their lives. His extension of development through adulthood and old age established the field of life course development. His emphasis on the impact of history and culture on development was a critical element in the developing field of ego psychology. Many of his major contributions can be fruitfully understood in the context of his personal history and individual qualities. PMID:9256525

  16. Erik Erikson: critical times, critical theory.

    PubMed

    Douvan, E

    1997-01-01

    The work and legacy of Erik Erikson are described in this brief outline of his career, his theories, and his impact on psychoanalysis, psychology, history, and the broader culture. His conception of the adolescent task-weaving internal tastes, talents, and values together with elements of one's life history and the demands of one's culture into a coherent identity-has had profound effects on developmental psychology and the way in which sophisticated youth construct and describe their lives. His extension of development through adulthood and old age established the field of life course development. His emphasis on the impact of history and culture on development was a critical element in the developing field of ego psychology. Many of his major contributions can be fruitfully understood in the context of his personal history and individual qualities.

  17. Minimum Critical Values Study

    SciTech Connect

    Fox, P.B.

    2005-07-11

    This report provides minimum critical values for various 30-cm water-reflected uranium and plutonium oxide and nitrate aqueous mixtures as calculated by the SCALE CSAS1X sequence using the 238-group ENDF/B-V neutron cross-section library. The minimum values were determined through parametric searches in one-dimensional geometry. The calculations have been performed to obtain the minimum values: critical volume and mass for spheres, critical radius for cylinders, critical thickness for slabs, and minimum critical concentration (infinite geometry) for the following homogeneous mixtures: (1) UO{sub 2}-H{sub 2}O for 3, 4, 5, 20, and 100 wt % {sup 235}U; (2) UNH for 3, 4, 5, 20, and 100 wt % {sup 235}U; (3) PuO{sub 2}-H{sub 2}O for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu); and (4) PuNH for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu). All bounding surfaces were fully reflected by 30 cm of H{sub 2}O.

  18. Nuclear criticality information system

    SciTech Connect

    Koponen, B.L.; Hampel, V.E.

    1981-11-30

    The nuclear criticality safety program at LLNL began in the 1950's with a critical measurements program which produced benchmark data until the late 1960's. This same time period saw the rapid development of computer technology useful for both computer modeling of fissile systems and for computer-aided management and display of the computational benchmark data. Database management grew in importance as the amount of information increased and as experimental programs were terminated. Within the criticality safety program at LLNL we began at that time to develop a computer library of benchmark data for validation of computer codes and cross sections. As part of this effort, we prepared a computer-based bibliography of criticality measurements on relatively simple systems. However, it is only now that some of these computer-based resources can be made available to the nuclear criticality safety community at large. This technology transfer is being accomplished by the DOE Technology Information System (TIS), a dedicated, advanced information system. The NCIS database is described.

  19. Predictability of critical transitions

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaozhu; Kuehn, Christian; Hallerberg, Sarah

    2015-11-01

    Critical transitions in multistable systems have been discussed as models for a variety of phenomena ranging from the extinctions of species to socioeconomic changes and climate transitions between ice ages and warm ages. From bifurcation theory we can expect certain critical transitions to be preceded by a decreased recovery from external perturbations. The consequences of this critical slowing down have been observed as an increase in variance and autocorrelation prior to the transition. However, especially in the presence of noise, it is not clear whether these changes in observation variables are statistically relevant such that they could be used as indicators for critical transitions. In this contribution we investigate the predictability of critical transitions in conceptual models. We study the quadratic integrate-and-fire model and the van der Pol model under the influence of external noise. We focus especially on the statistical analysis of the success of predictions and the overall predictability of the system. The performance of different indicator variables turns out to be dependent on the specific model under study and the conditions of accessing it. Furthermore, we study the influence of the magnitude of transitions on the predictive performance.

  20. Criticality in Plasma Membranes

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin; Papanikolaou, Stefanos; Sethna, James; Veatch, Sarah

    2011-03-01

    We are motivated by recent observations of micron-sized critical fluctuations in the 2d Ising Universality class in plasma membrane vesicles that are isolated from cortical cytoskeleton. We construct a minimal model of the plasma membrane's interaction with intact cytoskeleton which explains why large scale phase separation has not been observed in Vivo. In addition, we use analytical techniques from conformal field theory and numerical simulations to investigate the form of effective forces mediated by the membrane's proximity to criticality. We show that the range of this force is maximized near a critical point and we quantify its usefulness in mediating communication using techniques from information theory. Finally we use theoretical techniques from statistical physics in conjunction with Monte-Carlo simulations to understand how criticality can be used to increase the efficiency of membrane bound receptor mediated signaling. We expect that this sort of analysis will be broadly useful in understanding and quantifying the role of lipid ``rafts'' in a wide variety of membrane bound processes. Generally, we demonstrate that critical fluctuations provide a physical mechanism to organize and spatially segregate membrane components by providing channels for interaction over relatively large distances.

  1. Self-organized criticality

    SciTech Connect

    Per Bak ); Kan Chen )

    1991-01-01

    Just as the proverbial straw broke the camel's back, catastrophes, from earthquakes and avalanches to a stock market crash, can be triggered by a minor event. The authors argue that complex systems naturally evolve to a critical state. Their theory already has improved understanding of motion in the earth's crust, economies and ecosystems. The theory of self-organized criticality states that many composite systems naturally evolve to a critical state in which a minor event starts a chain reaction that can affect any number of elements in the system. Although composite systems produce more minor events than catastrophes, chain reactions of all sizes are an integral part of the dynamics. According to the theory, the mechanism that leads to minor events is the same one that leads to major events. Furthermore, composite systems never reach equilibrium but instead evolve from one metastable state to the next. Self-organized criticality is a holistic theory: the global features, such as the relative number of large and small events, do not depend on the microscopic mechanisms. Consequently, global features of the system cannot be understood by analyzing the parts separately. To the authors' knowledge, self-organized criticality is the only model or mathematical description that has led to a holistic theory for dynamic systems.

  2. Critical Management in Knowledge Organizations

    ERIC Educational Resources Information Center

    Macpherson, Reynold

    2008-01-01

    Purpose: The purpose of this paper is to invite educational managers and management educators to reflect critically on practice. Design/methodology/approach: Using the point of Socrates' death, the paper suggests ways of reflecting on actions using ethically-critical, socially-critical, environmentally-critical, politically-critical and…

  3. Critical Thinking in Business Education.

    ERIC Educational Resources Information Center

    Sormunen, Carolee

    Critical thinking is currently a prominent issue in education. For business educators, four issues must be considered: the meaning of critical thinking, how critical thinking can be introduced into the curriculum, how critical thinking is developed in courses, and how critical thinking can be evaluated. The literature identifies three theoretical…

  4. The Anatomy of Critical Discourse.

    ERIC Educational Resources Information Center

    Rosenfield, Lawrence W.

    1968-01-01

    Critical discourse is best understood when its logical features are identified. An examination of the basic elements and modes of rhetorical criticism (a form of critical discourse) produces a finite set of options for the critic, thus enabling him to develop a system of alternatives in his critical efforts. For example, by selecting from among…

  5. Morphogenesis at criticality?

    NASA Astrophysics Data System (ADS)

    Krotov, Dmitry; Dubuis, Julien; Gregor, Thomas; Bialek, William

    2014-03-01

    Spatial patterns in the early fruit fly embryo emerge from a network of interactions among transcription factors, the gap genes, driven by maternal inputs. Such networks can exhibit many qualitatively different behaviors, separated by critical surfaces. At criticality, we should observe strong correlations in the fluctuations of different genes around their mean expression levels, a slowing of the dynamics along some but not all directions in the space of possible expression levels, correlations of expression fluctuations over long distances in the embryo, and departures from a Gaussian distribution of these fluctuations. Analysis of recent experiments on the gap genes shows that all these signatures are observed, and that the different signatures are related in ways predicted by theory. While there might be other explanations for these individual phenomena, the confluence of evidence suggests that this genetic network is tuned to criticality.

  6. Interface localization near criticality

    NASA Astrophysics Data System (ADS)

    Delfino, Gesualdo

    2016-05-01

    The theory of interface localization in near-critical planar systems at phase coexistence is formulated from first principles. We show that mutual delocalization of two interfaces, amounting to interfacial wetting, occurs when the bulk correlation length critical exponent ν is larger than or equal to 1. Interaction with a boundary or defect line involves an additional scale and a dependence of the localization strength on the distance from criticality. The implications are particularly rich in the boundary case, where delocalization proceeds through different renormalization patterns sharing the feature that the boundary field becomes irrelevant in the delocalized regime. The boundary delocalization (wetting) transition is shown to be continuous, with surface specific heat and layer thickness exponents which can take values that we determine.

  7. Linear response at criticality

    NASA Astrophysics Data System (ADS)

    Svenkeson, Adam; Bologna, Mauro; Grigolini, Paolo

    2012-10-01

    We study a set of cooperatively interacting units at criticality, and we prove with analytical and numerical arguments that they generate the same renewal non-Poisson intermittency as that produced by blinking quantum dots, thereby giving a stronger support to the results of earlier investigation. By analyzing how this out-of-equilibrium system responds to harmonic perturbations, we find that the response can be described only using a new form of linear response theory that accounts for aging and the nonergodic behavior of the underlying process. We connect the undamped response of the system at criticality to the decaying response predicted by the recently established nonergodic fluctuation-dissipation theorem for dichotomous processes using information about the second moment of the fluctuations. We demonstrate that over a wide range of perturbation frequencies the response of the cooperative system is greatest when at criticality.

  8. Morphogenesis at criticality

    PubMed Central

    Krotov, Dmitry; Dubuis, Julien O.; Gregor, Thomas; Bialek, William

    2014-01-01

    Spatial patterns in the early fruit fly embryo emerge from a network of interactions among transcription factors, the gap genes, driven by maternal inputs. Such networks can exhibit many qualitatively different behaviors, separated by critical surfaces. At criticality, we should observe strong correlations in the fluctuations of different genes around their mean expression levels, a slowing of the dynamics along some but not all directions in the space of possible expression levels, correlations of expression fluctuations over long distances in the embryo, and departures from a Gaussian distribution of these fluctuations. Analysis of recent experiments on the gap gene network shows that all these signatures are observed, and that the different signatures are related in ways predicted by theory. Although there might be other explanations for these individual phenomena, the confluence of evidence suggests that this genetic network is tuned to criticality. PMID:24516161

  9. Militarily Critical Technology Program

    NASA Astrophysics Data System (ADS)

    Doherty, J.; Wick, R.; Sellers, P.

    The Militarily Critical Technology Program (MCTP) creates two technology lists: Militarily Critical Technology List (MCTL), which is focused on protecting US technology, and Developing Science and Technology List (DSTL). There are 20 different technology areas; two in particular are discussed in this poster paper, Space Systems Technologies and Lasers & Optics Technologies. The authors are the Technology Working Group chairs for Space Systems (Jim Doherty) and Lasers & Optics (Ray Wick), both from Institute for Defense Analyses (IDA), and also IDAs task leader for the MCTP (Paul Sellers).

  10. Critical Viscosity of Xenon

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. The sample cell at the heart of CVX-2 will sit inside a thermostat providing three layers of insulation. The cell itself comprises a copper body that conducts heat efficiently and smoothes out thermal variations that that would destroy the xenon's uniformity. Inside the cell, the oscillating screen viscometer element is supported between two pairs of electrodes that deflect the screen and then measure screen motion.

  11. Critical Viscosity of Xenon

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2001 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. The thermostat for CVX sits inside the white cylinder on a support structure that is placed inside a pressure canister. A similar canister holds the electronics and control systems. The CVX-2 arrangement is identical. The principal investigator is Dr. Robert F. Berg (not shown) of the National Institutes of Standards and Technology, Gaithersburg, MD. This is a detail view of MSFC 0100143.

  12. Translation as Literary Criticism.

    ERIC Educational Resources Information Center

    di Stefano, B. Follkart

    1982-01-01

    It is proposed that literary translation is intrinsically an act of literary criticism. This theory is illustrated by discussion of specific problems in translating Sartre's "La Nausee" and Leonard Forest's "Le pays de la Sagouine," especially the use of verb tense. (MSE)

  13. Conductive Critical Thinking

    ERIC Educational Resources Information Center

    Paetkau, Mark

    2007-01-01

    One of my goals as an instructor is to teach students critical thinking skills. This paper presents an example of a student-led discussion of heat conduction at the first-year level. Heat loss from a human head is calculated using conduction and radiation models. The results of these plausible (but wrong) models of heat transfer contradict what…

  14. Critical Incidents in Negotiation.

    ERIC Educational Resources Information Center

    American Association of School Administrators, Washington, DC.

    This report presents imaginary dialogues between a management team and an employee team and critiques the dialogues to emphasize the significance of situations and episodes that can hasten or hamper a settlement at the negotiation table. Three critical incidents are studied within each developmental phase of the negotiation process: (1) procedural…

  15. Criticizing the Role.

    ERIC Educational Resources Information Center

    Cohen, Arthur M.

    Critics of the community college are justified in challenging unsubstantiated statements about the institution by college spokespersons or in public relations releases disguised as institutional analyses. During the 1960's, for example, increasing enrollments were often cited as evidence of public support for community colleges--without reference…

  16. Creativity and Critical Thinking.

    ERIC Educational Resources Information Center

    Kollen, Patsy Phillips

    How to deal with the absence of creativity and critical thinking in the educational setting is discussed. All efforts to improve education will be futile if we don't take into account the absence of relationship among the participants and between the participants and the content of education. Relationship--i.e., connecting with others and with…

  17. SEMANTICS AND CRITICAL READING.

    ERIC Educational Resources Information Center

    FLANIGAN, MICHAEL C.

    PROFICIENCY IN CRITICAL READING CAN BE ACCELERATED BY MAKING STUDENTS AWARE OF VARIOUS SEMANTIC DEVICES THAT HELP CLARIFY MEANINGS AND PURPOSES. EXCERPTS FROM THE ARTICLE "TEEN-AGE CORRUPTION" FROM THE NINTH-GRADE SEMANTICS UNIT WRITTEN BY THE PROJECT ENGLISH DEMONSTRATION CENTER AT EUCLID, OHIO, ARE USED TO ILLUSTRATE HOW SEMANTICS RELATE TO…

  18. Audience, Style and Criticism

    ERIC Educational Resources Information Center

    Pimm, David; Sinclair, Nathalie

    2009-01-01

    The primary focus for this article involves aspects of professional mathematical writing and examines the possibility of a form of literary criticism in relation to it. By means of examples from contemporary style guides for academic articles in mathematics (AMS, MAA), as well as the writing of mathematicians (Hamilton, Dedekind) from earlier…

  19. Critical Thinking Concept Reconstructed

    ERIC Educational Resources Information Center

    Minter, Mary Kennedy

    2010-01-01

    This paper explores the proposition that teaching of critical thinking (CT) should include: (1) identifying and addressing the many environmental variables acting as barriers to our human thinking, i.e., an open system approach, and (2) utilizing the interrelatedness of the CT building blocks, i.e., creative thinking techniques, levels of…

  20. Replies to Criticisms

    ERIC Educational Resources Information Center

    Hamilton, James R.

    2009-01-01

    In this essay, Hamilton responds to criticisms of his book "The Art of Theater" (Malden, MA: Blackwell, 2007). Acknowledging that he expected that the central proposals in "The Art of Theater" would seem a little strange to philosophers, he reiterates his belief that the three general facts of any theatrical performance are its presentation, its…

  1. Critical Thinking and Learning

    ERIC Educational Resources Information Center

    Mason, Mark

    2007-01-01

    This paper introduces some of the debates in the field of critical thinking by highlighting differences among thinkers such as Siegel, Ennis, Paul, McPeck, and Martin, and poses some questions that arise from these debates. Does rationality transcend particular cultures, or are there different kinds of thinking, different styles of reasoning? What…

  2. Critical Practice: Teaching "Shakespeare."

    ERIC Educational Resources Information Center

    Mellor, Bronwyn; Patterson, Annette

    2000-01-01

    Describes how the authors taught their students to read "Hamlet" from a critical literacy perspective, analyzing how particular readings of texts and characters are constructed or produced; how they are determined by historical and cultural conventions; analyzing values that various readings support or challenge--rather than trying to get closer…

  3. Stateline: Critical Mass

    ERIC Educational Resources Information Center

    Christie, Kathy

    2005-01-01

    In Physics "critical mass" refers to the minimum amount of fissionable material required to sustain a chain reaction. The adoption of state education policy isn't often equated with this concept, but occasionally solutions and ideas seem to gather around a common problem. If the solution at hand is simple, easily understood, and strengthened with…

  4. Deconfined quantum critical points.

    PubMed

    Senthil, T; Vishwanath, Ashvin; Balents, Leon; Sachdev, Subir; Fisher, Matthew P A

    2004-03-01

    The theory of second-order phase transitions is one of the foundations of modern statistical mechanics and condensed-matter theory. A central concept is the observable order parameter, whose nonzero average value characterizes one or more phases. At large distances and long times, fluctuations of the order parameter(s) are described by a continuum field theory, and these dominate the physics near such phase transitions. We show that near second-order quantum phase transitions, subtle quantum interference effects can invalidate this paradigm, and we present a theory of quantum critical points in a variety of experimentally relevant two-dimensional antiferromagnets. The critical points separate phases characterized by conventional "confining" order parameters. Nevertheless, the critical theory contains an emergent gauge field and "deconfined" degrees of freedom associated with fractionalization of the order parameters. We propose that this paradigm for quantum criticality may be the key to resolving a number of experimental puzzles in correlated electron systems and offer a new perspective on the properties of complex materials.

  5. Light Touch Critical Friendship

    ERIC Educational Resources Information Center

    Swaffield, Sue

    2007-01-01

    Critical friendship is a flexible form of support for school colleagues and one that is increasingly being applied to different contexts, including the New Relationship with Schools and School Improvement Partners. The ESRC/TLRP "Learning How to Learn" (LHTL) project was interested in, among other things, the scaling up of innovation, and…

  6. Critical Skills Survey

    ERIC Educational Resources Information Center

    Education Digest: Essential Readings Condensed for Quick Review, 2010

    2010-01-01

    As the U.S. economy begins to show signs of improvement, executives say they need a workforce fully equipped with skills beyond just the basics of reading, writing, and arithmetic (the three Rs). Skills such as critical thinking and problem solving, communication, collaboration, and creativity and innovation (the four Cs) will become even more…

  7. Educational Criticism and Shamanism.

    ERIC Educational Resources Information Center

    Sevigny, Maurice J.

    1984-01-01

    Critiqued is the article, "Teacher as Shaman: An Educational Criticism," (Studies in Art Education, v25 n1), containing a case study of an art teacher who employs performance-based ritual to stimulate thinking about art's meaning and history. The problem that ethnographic researchers have conveying credibility when summarizing investigations is…

  8. Molecular characterization of the marker chromosome associated with cat eye syndrome

    SciTech Connect

    Mears, A.J.; McDermid, H.E. ); Duncan, A.M.V. ); Budarf, M.L.; Emanuel, B.S.; Sellinger, B. ); Siegel-Bartelt, J. ); Greenberg, C.R. )

    1994-07-01

    Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study the authors have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2. 35 refs., 3 figs., 2 tabs.

  9. Critical Education, Critical Pedagogies, Marxist Education in the United States

    ERIC Educational Resources Information Center

    Foley, Jean Ann; Morris, Doug; Gounari, Panayota; Agostinone-Wilson, Faith

    2015-01-01

    As critical pedagogy becomes more mainstream on the educational landscape in the United States, it is important to revisit the original tenets of critical pedagogy and explore their current manifestations. Since the beginning of "criticalism" from the theoretical/foundational work of the Frankfurt School of Critical Social Theory,…

  10. Critical Viscosity of Xenon

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of liquid xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Resembling a tiny bit of window screen, the oscillator at the heart of CVX-2 will vibrate between two pairs of paddle-like electrodes. The slight bend in the shape of the mesh has no effect on the data. What counts are the mesh's displacement in the xenon fluid and the rate at which the displacement dampens. The unit shown here is encased in a small test cell and capped with a sapphire windown to contain the xenon at high pressure.

  11. Critical dynamics and decoherence

    SciTech Connect

    Damski, Bogdan; Quan, Haitao T; Zurek, Wojciech H

    2009-01-01

    We study dynamics of decoherence in a generic model where the environment is driven and undergoes a quantum phase transition. We model the environment by the Ising chain in the transverse field, and assume that the decohering system is a central spin-1/2. We found that when the environment is quenched slowly through the critical point, the decoherence factor of the central spin undergoes rapid decay that encodes the critical exponents of the environment. We also found that decoherence in a non-equilibrated, kink-contaminated, environment can be stronger than in a vacuum one. We derived a remarkably simple analytical expression that describes post-transition decoherence and predicts periodicities involving all system parameters. This research connects the fields of decoherence, quantum phase transitions, and Kibble-Zurek non-equilibrium dynamics.

  12. Critical branching neural networks.

    PubMed

    Kello, Christopher T

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical branching and, in doing so, simulates observed scaling laws as pervasive to neural and behavioral activity. These scaling laws are related to neural and cognitive functions, in that critical branching is shown to yield spiking activity with maximal memory and encoding capacities when analyzed using reservoir computing techniques. The model is also shown to account for findings of pervasive 1/f scaling in speech and cued response behaviors that are difficult to explain by isolable causes. Issues and questions raised by the model and its results are discussed from the perspectives of physics, neuroscience, computer and information sciences, and psychological and cognitive sciences.

  13. Critical care in India.

    PubMed

    Udwadia, F E; Guntupalli, K K; Vidyasagar, D

    1997-04-01

    India is a vast democracy of nearly one billion people. Before the British rule ended in 1947, the life span of an Indian was a mere 21 years. Within a short span of 50 years, it increased to an impressive 63 years, largely due to public health measures initiated by the government. This created a pool of more than 300 million middle class Indians who could afford the benefits of modern and specialized care when needed. Critical care medicine, as practiced in the West, is still confined to large Metropolitan areas. A large pool of expatriate Indian physicians from all over the world are helping bridge the resource gap between the West and India by transfer of technology and providing appropriate training to physicians and paramedical personnel. This article describes the history and current status of development of critical care medicine in India. PMID:9107510

  14. Carahunge - A Critical Assessment

    NASA Astrophysics Data System (ADS)

    González-García, A. César

    Carahunge is a megalithic monument in southern Armenia that has often been acclaimed as the oldest observatory. The monument, composed of dozens of standing stones, has some perforated stones. The direction of the holes has been measured and their orientation is related to the sun, moon, and stars, obtaining a date for the construction of such devices. After a critical review of the methods and conclusions, these are shown as untenable.

  15. Criticality safety training

    SciTech Connect

    Woodruff, S.K.

    1997-06-01

    Criticality safety training is an important element of the Plutonium Facility safety program at Los Alamos National Laboratory. Training consists of student self-study handbooks and hands-on performance-based training in a mock-up laboratory containing gloveboxes, trolley conveyor system, and self-monitoring instruments. A 10-minute video tape and lecture was presented to describe how training in this area is conducted.

  16. Horizon as critical phenomenon

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Sik

    2016-09-01

    We show that renormalization group flow can be viewed as a gradual wave function collapse, where a quantum state associated with the action of field theory evolves toward a final state that describes an IR fixed point. The process of collapse is described by the radial evolution in the dual holographic theory. If the theory is in the same phase as the assumed IR fixed point, the initial state is smoothly projected to the final state. If in a different phase, the initial state undergoes a phase transition which in turn gives rise to a horizon in the bulk geometry. We demonstrate the connection between critical behavior and horizon in an example, by deriving the bulk metrics that emerge in various phases of the U( N ) vector model in the large N limit based on the holographic dual constructed from quantum renormalization group. The gapped phase exhibits a geometry that smoothly ends at a finite proper distance in the radial direction. The geometric distance in the radial direction measures a complexity: the depth of renormalization group transformation that is needed to project the generally entangled UV state to a direct product state in the IR. For gapless states, entanglement persistently spreads out to larger length scales, and the initial state can not be projected to the direct product state. The obstruction to smooth projection at charge neutral point manifests itself as the long throat in the anti-de Sitter space. The Poincare horizon at infinity marks the critical point which exhibits a divergent length scale in the spread of entanglement. For the gapless states with non-zero chemical potential, the bulk space becomes the Lifshitz geometry with the dynamical critical exponent two. The identification of horizon as critical point may provide an explanation for the universality of horizon. We also discuss the structure of the bulk tensor network that emerges from the quantum renormalization group.

  17. Critical Path Web Site

    NASA Technical Reports Server (NTRS)

    Robinson, Judith L.; Charles, John B.; Rummel, John A. (Technical Monitor)

    2000-01-01

    Approximately three years ago, the Agency's lead center for the human elements of spaceflight (the Johnson Space Center), along with the National Biomedical Research Institute (NSBRI) (which has the lead role in developing countermeasures) initiated an activity to identify the most critical risks confronting extended human spaceflight. Two salient factors influenced this activity: first, what information is needed to enable a "go/no go" decision to embark on extended human spaceflight missions; and second, what knowledge and capabilities are needed to address known and potential health, safety and performance risks associated with such missions. A unique approach was used to first define and assess those risks, and then to prioritize them. This activity was called the Critical Path Roadmap (CPR) and it represents an opportunity to develop and implement a focused and evolving program of research and technology designed from a "risk reduction" perspective to prevent or minimize the risks to humans exposed to the space environment. The Critical Path Roadmap provides the foundation needed to ensure that human spaceflight, now and in the future, is as safe, productive and healthy as possible (within the constraints imposed on any particular mission) regardless of mission duration or destination. As a tool, the Critical Path Roadmap enables the decision maker to select from among the demonstrated or potential risks those that are to be mitigated, and the completeness of that mitigation. The primary audience for the CPR Web Site is the members of the scientific community who are interested in the research and technology efforts required for ensuring safe and productive human spaceflight. They may already be informed about the various space life sciences research programs or they may be newcomers. Providing the CPR content to potential investigators increases the probability of their delivering effective risk mitigations. Others who will use the CPR Web Site and its

  18. Critical Path Web Site

    NASA Technical Reports Server (NTRS)

    Robinson, Judith L.; Charles, John B.; Rummel, John A. (Technical Monitor)

    2000-01-01

    Approximately three years ago, the Agency's lead center for the human elements of spaceflight (the Johnson Space Center), along with the National Biomedical Research Institute (NSBRI) (which has the lead role in developing countermeasures) initiated an activity to identify the most critical risks confronting extended human spaceflight. Two salient factors influenced this activity: first, what information is needed to enable a "go/no go" decision to embark on extended human spaceflight missions; and second, what knowledge and capabilities are needed to address known and potential health, safety and performance risks associated with such missions. A unique approach was used to first define and assess those risks, and then to prioritize them. This activity was called the Critical Path Roadmap (CPR) and it represents an opportunity to develop and implement a focused and evolving program of research and technology designed from a "risk reduction" perspective to prevent or minimize the risks to humans exposed to the space environment. The Critical Path Roadmap provides the foundation needed to ensure that human spaceflight, now and in the future, is as safe, productive and healthy as possible (within the constraints imposed on any particular mission) regardless of mission duration or destination. As a tool, the Critical Path Roadmap enables the decisionmaker to select from among the demonstrated or potential risks those that are to be mitigated, and the completeness of that mitigation. The primary audience for the CPR Web Site is the members of the scientific community who are interested in the research and technology efforts required for ensuring safe and productive human spaceflight. They may already be informed about the various space life sciences research programs or they may be newcomers. Providing the CPR content to potential investigators increases the probability of their delivering effective risk mitigations. Others who will use the CPR Web Site and its content

  19. Challenges in Critical Language Teaching

    ERIC Educational Resources Information Center

    Pessoa, Rosane Rocha; de Urzeda Freitas, Marco Tulio

    2012-01-01

    This article is based on the conception of language teaching as a liberatory practice. Drawing on some principles of critical pedagogy (Ellsworth, 1992; Freire, 2005; hooks, 1994; Norton & Toohey, 2004), critical applied linguistics (Pennycook, 1990, 2001), critical language teaching (Ferreira, 2006; Pennycook, 1999), and critical language teacher…

  20. Morphogenesis at criticality?

    NASA Astrophysics Data System (ADS)

    Krotov, Dmitry; Dubuis, Julien; Wieschaus, Eric; Gregor, Thomas; Bialek, William

    2013-03-01

    Embryonic development of many multicellular organisms begins with the generation of spatially varying patterns of morphogens that encode the body plan of the future organism. We study the spatial pattern formed by the gap gene proteins in the early fruit fly embryo, which is anchored by ``crossing points'' between expression levels of different genes; these are thought to result from mutual repression. We explore a broad class of models for such interacting genes and show that the parameters implied implied by recent quantitative measurements are non-generic, but rather tuned to certain values, so that the entire gap gene network operates close to the critical surface in its phase diagram. We develop a mean field description of this system as well as derive signatures of critical behavior in the structure of expression noise. One such signature is that fluctuations are dominated by a single ``massless'' mode, so that fluctuations of expression levels of different genes are highly correlated/anticorrelated. We find a surprisingly high degree of anticorrelation in the real experimental data. These results suggest an interesting possibility that the network of genes responsible for development is operating near criticality.

  1. [The critical scientists' voice].

    PubMed

    Lewgoy, F

    2000-01-01

    The intricate debate over genetically modified organisms (GMOs) involves powerful economic interests, as well as ethical, legal, emotional and scientific aspects, some of which are dealt with in this paper.(It is possible to identify two main groups of scientists across the GMOs divide: the triumphalist and the critical group.) Scientists in the triumphalist group state that GMOs and their derivatives are safe for the environment and do not offer health hazards any more than similar, non-genetically modified, products. This view is disputed by the critical scientists, who are prompted by the scarcity of studies on the environmental impacts and toxicity of GMOs, and who point out flaws in tests performed by the same companies which hold the patents. They are also critical of the current state of the process of gene transference, lacking accuracy, a fact which, coupled with the scant knowledge available about 97% of the genome functions, may produce unforseeable effects with risks for the environment and public health yet to be assessed. Examples of such effects are: the transference of alien genes [??] to other species, the emergence of toxins, the creation of new viruses, the impacts on beneficial insects and on biodiversity in general.

  2. Relative Critical Points

    NASA Astrophysics Data System (ADS)

    Lewis, Debra

    2013-05-01

    Relative equilibria of Lagrangian and Hamiltonian systems with symmetry are critical points of appropriate scalar functions parametrized by the Lie algebra (or its dual) of the symmetry group. Setting aside the structures - symplectic, Poisson, or variational - generating dynamical systems from such functions highlights the common features of their construction and analysis, and supports the construction of analogous functions in non-Hamiltonian settings. If the symmetry group is nonabelian, the functions are invariant only with respect to the isotropy subgroup of the given parameter value. Replacing the parametrized family of functions with a single function on the product manifold and extending the action using the (co)adjoint action on the algebra or its dual yields a fully invariant function. An invariant map can be used to reverse the usual perspective: rather than selecting a parametrized family of functions and finding their critical points, conditions under which functions will be critical on specific orbits, typically distinguished by isotropy class, can be derived. This strategy is illustrated using several well-known mechanical systems - the Lagrange top, the double spherical pendulum, the free rigid body, and the Riemann ellipsoids - and generalizations of these systems.

  3. Criticality validation for burnup credit using recycle Pu criticals

    SciTech Connect

    Fuentes, E.; Lancaster, D.

    1997-04-01

    A set of 23 additional critical experiments were analyzed to provide additional input to the criticality validation portion of spent fuel cask analysis. The results of this analyses were combined with the previously analyzed criticals to determine the upper safety limit on k{sub eff}. The combined set of criticals can be used used for criticality validation for burnup credit, and are better suited for the range of isotopics in spent nuclear fuels. A trend observed in the analysis was that the calculated k{sub eff} deviates from the criticals in the positive direction, implying that increased burnup results in increased safety margin. 6 refs., 2 figs., 1 tab.

  4. Safety Critical Mechanisms

    NASA Technical Reports Server (NTRS)

    Robertson, Brandan

    2008-01-01

    Spaceflight mechanisms have a reputation for being difficult to develop and operate successfully. This reputation is well earned. Many circumstances conspire to make this so: the environments in which the mechanisms are used are extremely severe, there is usually limited or no maintenance opportunity available during operation due to this environment, the environments are difficult to replicate accurately on the ground, the expense of the mechanism development makes it impractical to build and test many units for long periods of time before use, mechanisms tend to be highly specialized and not prone to interchangeability or off-the-shelf use, they can generate and store a lot of energy, and the nature of mechanisms themselves, as a combination of structures, electronics, etc. designed to accomplish specific dynamic performance, makes them very complex and subject to many unpredictable interactions of many types. In addition to their complexities, mechanism are often counted upon to provide critical vehicle functions that can result in catastrophic events should the functions not be performed. It is for this reason that mechanisms are frequently subjected to special scrutiny in safety processes. However, a failure tolerant approach, along with good design and development practices and detailed design reviews, can be developed to allow such notoriously troublesome mechanisms to be utilized confidently in safety-critical applications.

  5. Rethinking Critical Adsorption

    NASA Astrophysics Data System (ADS)

    Franck, Carl; Peach, Sarah; Polak, Robert D.

    1996-03-01

    Recent reflectivity experiments on near-critical mixtures of carbon disulfide and nitromethane contained in glass cells footnote Niraj S. Desai, Sarah Peach, and Carl Franck, Phys. Rev. E 52, 4129 (1995) have shown that preferential adsorption of one liquid component onto the wall can be controlled by chemical modification of the glass. The glass was treated with varying amounts of hexamethyldisilazane to decrease surface polarity and therefore enhance the adsorption of carbon disulfide in a surprisingly continuous way. The effect of the glass wall on the local liquid composition can be described by two different scaling hypotheses: using a short range field on the liquid closest to the wall, or pinning the amplitude of the order parameter at the surface. We have found that only the second approach is consistent with the experimental data, although this is difficult to reconcile with observed wetting critical phenomena. We also have reexamined the issue of substrate inhomogeneity and conclude that the substrates were indeed homogeneous on relevant length scales. Supported by the NSF under DMR-9320910 and the central facilities of the Materials Science Center at Cornell University.

  6. Design of Critical Components

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Zaretsky, Erwin V.

    2001-01-01

    Critical component design is based on minimizing product failures that results in loss of life. Potential catastrophic failures are reduced to secondary failures where components removed for cause or operating time in the system. Issues of liability and cost of component removal become of paramount importance. Deterministic design with factors of safety and probabilistic design address but lack the essential characteristics for the design of critical components. In deterministic design and fabrication there are heuristic rules and safety factors developed over time for large sets of structural/material components. These factors did not come without cost. Many designs failed and many rules (codes) have standing committees to oversee their proper usage and enforcement. In probabilistic design, not only are failures a given, the failures are calculated; an element of risk is assumed based on empirical failure data for large classes of component operations. Failure of a class of components can be predicted, yet one can not predict when a specific component will fail. The analogy is to the life insurance industry where very careful statistics are book-kept on classes of individuals. For a specific class, life span can be predicted within statistical limits, yet life-span of a specific element of that class can not be predicted.

  7. Critical Literature Pedagogy: Teaching Canonical Literature for Critical Literacy

    ERIC Educational Resources Information Center

    Borsheim-Black, Carlin; Macaluso, Michael; Petrone, Robert

    2014-01-01

    This article introduces Critical Literature Pedagogy (CLP), a pedagogical framework for applying goals of critical literacy within the context of teaching canonical literature. Critical literacies encompass skills and dispositions to understand, question, and critique ideological messages of texts; because canonical literature is often…

  8. The Moral Imperative of Criticism

    ERIC Educational Resources Information Center

    Hillbruner, Anthony

    1975-01-01

    Elaborates on the ethical responsibility of the rhetorical critic and teacher. The role that moral values play in the criticism process are examined in the literature, history and philosophy disciplines. (MH)

  9. Creative critical-thinking strategies.

    PubMed

    Chubinski, S

    1996-01-01

    Are you looking for strategies to teach critical thinking? The author presents a variety of quick, creative strategies to facilitate teaching critical-thinking skills. These strategies engage students in their learning and are adaptable to any nursing course.

  10. Critical Density Interaction Studies

    SciTech Connect

    Young, P; Baldis, H A; Cheung, P; Rozmus, W; Kruer, W; Wilks, S; Crowley, S; Mori, W; Hansen, C

    2001-02-14

    Experiments have been performed to study the propagation of intense laser pulses to high plasma densities. The issue of self-focusing and filamentation of the laser pulse as well as developing predictive capability of absorption processes and x-ray conversion efficiencies is important for numerous programs at the Laboratory, particularly Laser Program (Fast Ignitor and direct-drive ICF) and D&NT (radiography, high energy backlighters and laser cutting). Processes such as resonance absorption, profile modification, linear mode conversion, filamentation and stimulated Brillouin scattering can occur near the critical density and can have important effects on the coupling of laser light to solid targets. A combination of experiments have been used to study the propagation of laser light to high plasma densities and the interaction physics of intense laser pulses with solid targets. Nonparaxial fluid codes to study nonstationary behavior of filamentation and stimulated Brillouin scattering at high densities have also been developed as part of this project.

  11. Critical Infrastructure Modeling System

    2004-10-01

    The Critical Infrastructure Modeling System (CIMS) is a 3D modeling and simulation environment designed to assist users in the analysis of dependencies within individual infrastructure and also interdependencies between multiple infrastructures. Through visual cuing and textual displays, a use can evaluate the effect of system perturbation and identify the emergent patterns that evolve. These patterns include possible outage areas from a loss of power, denial of service or access, and disruption of operations. Method ofmore » Solution: CIMS allows the user to model a system, create an overlay of information, and create 3D representative images to illustrate key infrastructure elements. A geo-referenced scene, satellite, aerial images or technical drawings can be incorporated into the scene. Scenarios of events can be scripted, and the user can also interact during run time to alter system characteristics. CIMS operates as a discrete event simulation engine feeding a 3D visualization.« less

  12. Actuating critical care therapeutics.

    PubMed

    Stone, David J; Csete, Marie

    2016-10-01

    Viewing the intensive care unit (ICU) as a control system with inputs (patients) and outputs (outcomes), we focus on actuation (therapies) of the system and how to enhance our understanding of status of patients and their trajectory in the ICU. To incorporate the results of these analytics meaningfully, we feel that a reassessment of predictive scoring systems and of ways to optimally characterize and display the patient's "state space" to clinicians is important. Advances in sensing (diagnostics) and computation have not yet led to significantly better actuation, and so we focus on ways that data can be used to improve actuation in the ICU, in particular by following therapeutic burden along with disease severity. This article is meant to encourage discussion about how the critical care community can best deal with the data they see each day, and prepare for recommendations that will inevitably arise from application of major federal and state initiatives in big data analytics and precision medicine.

  13. Critical CRBR core pressure

    SciTech Connect

    Ju, F.D.

    1980-06-01

    The conditions are detailed under which gas pressure will cause or initiate failure in the structural containment of the fuel core. The Clinch River Breeder Reactor Plant is the prototype structure. Two general classes of problems have been studied, representing two entirely distinct configurations of containment failure. The first model determines the minimum pressure to lift a portion or the entire core from its containment. The second model estimates the critical pressure above which the fuel rods interior to the hexagonal fuel can warp, leading to blockage of the gas passages. Such blockage might cause further buildup of the gas pressure to a level causing the failure of the fuel rod containment in the hexagonal fuel container.

  14. Critical anthropometry for menarche.

    PubMed

    Gonzales, G F; Villena, A

    1996-08-01

    The objective of the study was to determine if any anthropometric measurements, including weight, height, and upper arm circumference, or the calculated body mass index observed at the time of menarche may be used as a threshold for menarche. The sample was randomly selected from 1133 girls aged 10-18 years from two groups, one residing in Lima, Peru, at 150 m above sea level, and the second in Cerro de Pasco, Peru, at 4340 m above sea level. For the purpose of this study, all girls who reached menarche at least 1 month before the study (n = 93) were considered as cases (girls at menarche); 88 girls without menarche at the time of the study were randomly matched by age and place of residence, and designated as controls. All subjects came from the same low socioeconomic status. Body weight at menarche was 44.6 +/- 5.09 kg (mean +/- SD; coefficient of variation [CV], 11.4%). Height at menarche was 151.6 +/- 5.5 cm (CV, 3.7%). Body mass index, defined as weight/height2.15, was 18.26 +/- 1.96 kg/m2.15 at menarche (CV, 10.7%). Upper arm circumference at menarche was 21.8 +/- 1.6 cm (CV, 7.3%). The logistic regression analysis showed that any of the four anthropometric measurements analyzed were critical for menarche; i.e., any of the four could be used as a threshold for menarche. Data from the present study do not support the hypothesis that there are anthropometric markers that are critical for menarche.

  15. Against the Bureaucratization of Criticism.

    ERIC Educational Resources Information Center

    Nothstine, William L.; Copeland, Gary A.

    The proliferation of critics and critical approaches has produced a trend toward fragmentation and isolation among the practitioners involved. A suggestive counter-trend indicates that there is intense curiosity among critics to watch colleagues encounter texts, grapple with the preliminary questions of stance and method, and share the experience…

  16. A Critically Reflective Social Studies?

    ERIC Educational Resources Information Center

    Clarke, Marge

    1990-01-01

    Examines social studies in the twenty-first century from a critical theory perspective. Traces critical reflection's origins from Marxist educational theories to Jurgen Habermas's critical theory. Highlights Fred Newmann's curricular model, "Education for Citizen Action," for developing competent action in public affairs. Advocates infusing…

  17. Word Recognition and Critical Reading.

    ERIC Educational Resources Information Center

    Groff, Patrick

    1991-01-01

    This article discusses the distinctions between literal and critical reading and explains the role that word recognition ability plays in critical reading behavior. It concludes that correct word recognition provides the raw material on which higher order critical reading is based. (DB)

  18. Critical Quantitative Inquiry in Context

    ERIC Educational Resources Information Center

    Stage, Frances K.; Wells, Ryan S.

    2014-01-01

    This chapter briefly traces the development of the concept of critical quantitative inquiry, provides an expanded conceptualization of the tasks of critical quantitative research, offers theoretical explanation and justification for critical research using quantitative methods, and previews the work of quantitative criticalists presented in this…

  19. What Is Critical about Sociology?

    ERIC Educational Resources Information Center

    Buechler, Steven

    2008-01-01

    Critical thinking is often presented as a generic technique. This article develops an alternative that links critique more closely to the sociological perspective. I suggest three answers to the above question: that the sociological perspective is critical for comprehending complex issues, that all sociology is implicitly critical by virtue of its…

  20. Applying critical thinking to nursing.

    PubMed

    Price, Bob

    2015-08-19

    Critical thinking and writing are skills that are not easy to acquire. The term 'critical' is used differently in social and clinical contexts. Nursing students need time to master the inquisitive and ruminative aspects of critical thinking that are required in academic environments. This article outlines what is meant by critical thinking in academic settings, in relation to both theory and reflective practice. It explains how the focus of a question affects the sort of critical thinking required and offers two taxonomies of learning, to which students can refer when analysing essay requirements. The article concludes with examples of analytical writing in reference to theory and reflective practice.

  1. Are Earthquakes a Critical Phenomenon?

    NASA Astrophysics Data System (ADS)

    Ramos, O.

    2014-12-01

    Earthquakes, granular avalanches, superconducting vortices, solar flares, and even stock markets are known to evolve through power-law distributed events. During decades, the formalism of equilibrium phase transition has coined these phenomena as critical, which implies that they are also unpredictable. This work revises these ideas and uses earthquakes as the paradigm to demonstrate that slowly driven systems evolving through uncorrelated and power-law distributed avalanches (UPLA) are not necessarily critical systems, and therefore not necessarily unpredictable. By linking the correlation length to the pdf of the distribution, and comparing it with the one obtained at a critical point, a condition of criticality is introduced. Simulations in the classical Olami-Feder-Christensen (OFC) earthquake model confirm the findings, showing that earthquakes are not a critical phenomenon. However, one single catastrophic earthquake may show critical properties and, paradoxically, the emergence of this temporal critical behaviour may eventually carry precursory signs of catastrophic events.

  2. Osteoarthritis: A Critical Review

    PubMed Central

    Onishi, Kentaro; Utturkar, Amol; Chang, Eric; Panush, Richard; Hata, Justin; Perret-Karimi, Danielle

    2015-01-01

    Patients with osteoarthritis (OA) are faced with a barrage of treatment options, from recommendations from friends and social media to medications prescribed by the primary care physician. The purpose of this article is to critically review current approaches to generalized or monoarticular OA based on available evidence and to illustrate multidisciplinary and multimodal treatment strategies for the management of OA. Treatment options assessed for efficacy include patient education; oral and topical pharmacological agents; complementary and alternative medicine; surgery; manual medicine; acupuncture; interventional procedures (corticosteroid injection, viscosupplementation, and pulsed radiofrequency); bracing; assistive devices; physical therapy; and physical modalities. Multidisciplinary and multimodal treatment strategies combined with early detection and prevention strategies provide the best benefit to patients. This review also illustrates that traditional and alternative modalities of treatment can be both synergistic and beneficial. Physicians should be aware of the variety of tools available for the management of OA and the associated symptoms. Those healthcare providers who can best individualize treatment plans for specific patients and inspire their patients to embrace healthy lifestyle modifications will achieve the best results. PMID:25750483

  3. Sepsis in critical care.

    PubMed

    King, Joan E

    2007-03-01

    Sepsis is a syndrome produced by the accelerated activity of the inflammatory immune response, the clotting cascade, and endothelial damage. It is a systematic process that can progress easily into septic shock and MODS. The chemical mediators or cytokines produce a complex self-perpetuating process that impacts all body systems. It is critical for the nurse first to identify patients at risk for developing sepsis and to assess patients who have SIRS and sepsis continually for signs and symptoms of organ involvement and organ dysfunction. Once sepsis has been diagnosed, evidence-based practice indicates initiation of fluid resuscitation. Vasopressor therapy, positive inotropic support, and appropriate antibiotic therapy should be started within the first hour. Within a 6-hour timeframe the goal is stabilization of the CVP, MAP, and UOP to prevent further organ damage. The challenge for nurses caring for septic patients is to support the treatment goals, to prevent added complications including stress ulcers, DVTs, aspiration pneumonia, and the progression to MODS, and to address the patient's and the family's psychosocial needs. As complex as the pathophysiology of sepsis is, the nursing care is equally complex but also rewarding. Patients who previously might have died now recover as vigilant nursing care combines forces with new drug therapies and evidence-based practice guidelines.

  4. Thermionic critical technology investigation

    NASA Astrophysics Data System (ADS)

    Jalichandra, P.; Hamerdinger, R. W.; Anderson, E. A.; Lamp, T. R.; Donovan, B. D.

    The thermionic critical technology investigation was initiated to enrich the technology base for thermionic space nuclear power systems. The focus of this program is on an out-of-core, Romashka type reactor system which can operate in the 5-40-kW range. The Romashka concept uses uranium carbide fuel in graphite trays which are radiatively coupled to planar thermionic converters. After completion of the design and fabrication of two state-of-the-art baseline converters, the baseline converters have been subject to further performance and life testing. To date, converter performance tests have been conducted for emitter temperatures from 1850 to 2000 K. The studies have shown that a thermionic converter with a heat-pipe-cooled collector is capable of high power conversion efficiency. By selecting the rhenium-rhenium system, in a closely spaced ignited mode converter, conversion efficiencies of 14 percent with a cell potential of 0.7 V can be readily attained. The sodium heat pipe provides a buffer against extreme changes in collector temperature due to fluctuations in converter load, one that can be improved upon by loading with an inert gas.

  5. Cohort: critical science

    NASA Astrophysics Data System (ADS)

    Digney, Bruce L.

    2007-04-01

    Unmanned vehicle systems is an attractive technology for the military, but whose promises have remained largely undelivered. There currently exist fielded remote controlled UGVs and high altitude UAV whose benefits are based on standoff in low complexity environments with sufficiently low control reaction time requirements to allow for teleoperation. While effective within there limited operational niche such systems do not meet with the vision of future military UxV scenarios. Such scenarios envision unmanned vehicles operating effectively in complex environments and situations with high levels of independence and effective coordination with other machines and humans pursing high level, changing and sometimes conflicting goals. While these aims are clearly ambitious they do provide necessary targets and inspiration with hopes of fielding near term useful semi-autonomous unmanned systems. Autonomy involves many fields of research including machine vision, artificial intelligence, control theory, machine learning and distributed systems all of which are intertwined and have goals of creating more versatile broadly applicable algorithms. Cohort is a major Applied Research Program (ARP) led by Defence R&D Canada (DRDC) Suffield and its aim is to develop coordinated teams of unmanned vehicles (UxVs) for urban environments. This paper will discuss the critical science being addressed by DRDC developing semi-autonomous systems.

  6. Teaching critical thinking

    PubMed Central

    Holmes, N. G.; Wieman, Carl E.; Bonn, D. A.

    2015-01-01

    The ability to make decisions based on data, with its inherent uncertainties and variability, is a complex and vital skill in the modern world. The need for such quantitative critical thinking occurs in many different contexts, and although it is an important goal of education, that goal is seldom being achieved. We argue that the key element for developing this ability is repeated practice in making decisions based on data, with feedback on those decisions. We demonstrate a structure for providing suitable practice that can be applied in any instructional setting that involves the acquisition of data and relating that data to scientific models. This study reports the results of applying that structure in an introductory physics laboratory course. Students in an experimental condition were repeatedly instructed to make and act on quantitative comparisons between datasets, and between data and models, an approach that is common to all science disciplines. These instructions were slowly faded across the course. After the instructions had been removed, students in the experimental condition were 12 times more likely to spontaneously propose or make changes to improve their experimental methods than a control group, who performed traditional experimental activities. The students in the experimental condition were also four times more likely to identify and explain a limitation of a physical model using their data. Students in the experimental condition also showed much more sophisticated reasoning about their data. These differences between the groups were seen to persist into a subsequent course taken the following year. PMID:26283351

  7. Teaching critical thinking.

    PubMed

    Holmes, N G; Wieman, Carl E; Bonn, D A

    2015-09-01

    The ability to make decisions based on data, with its inherent uncertainties and variability, is a complex and vital skill in the modern world. The need for such quantitative critical thinking occurs in many different contexts, and although it is an important goal of education, that goal is seldom being achieved. We argue that the key element for developing this ability is repeated practice in making decisions based on data, with feedback on those decisions. We demonstrate a structure for providing suitable practice that can be applied in any instructional setting that involves the acquisition of data and relating that data to scientific models. This study reports the results of applying that structure in an introductory physics laboratory course. Students in an experimental condition were repeatedly instructed to make and act on quantitative comparisons between datasets, and between data and models, an approach that is common to all science disciplines. These instructions were slowly faded across the course. After the instructions had been removed, students in the experimental condition were 12 times more likely to spontaneously propose or make changes to improve their experimental methods than a control group, who performed traditional experimental activities. The students in the experimental condition were also four times more likely to identify and explain a limitation of a physical model using their data. Students in the experimental condition also showed much more sophisticated reasoning about their data. These differences between the groups were seen to persist into a subsequent course taken the following year.

  8. Criticality in the brain

    NASA Astrophysics Data System (ADS)

    de Arcangelis, L.; Lombardi, F.; Herrmann, H. J.

    2014-03-01

    Spontaneous brain activity has been recently characterized by avalanche dynamics with critical features for systems in vitro and in vivo. In this contribution we present a review of experimental results on neuronal avalanches in cortex slices, together with numerical results from a neuronal model implementing several physiological properties of living neurons. Numerical data reproduce experimental results for avalanche statistics. The temporal organization of avalanches can be characterized by the distribution of waiting times between successive avalanches. Experimental measurements exhibit a non-monotonic behaviour, not usually found in other natural processes. Numerical simulations provide evidence that this behaviour is a consequence of the alternation between states of high and low activity, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homoeostatic mechanisms. Interestingly, the same homoeostatic balance is detected for neuronal activity at the scale of the whole brain. We finally review the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules and the learning dynamics exhibits universal features as a function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  9. Critical dynamics in microgravity

    SciTech Connect

    Duncan, R.; Boyd, S.; Akau, R.; Gianoulakis, S.

    1996-05-01

    Although many well-controlled experiments have been conducted to measure the static properties of systems near criticality, few experiments have explored the transport properties in systems driven very far away from equilibrium as the transition occurs. Here we propose to measure the thermal gradient across the superfluid (HeII)-normal fluid (HeI) interface in microgravity conditions as a function of the heat flux Q used to make the measurements. Microgravity conditions are required (1) to avoid the hydrostatic pressure variation along the height of the helium column (a concern for Q<0.1 {mu}W {center_dot}cm {sup {minus}2}), (2) avoid convection in He-I for Q> 3 {mu}W {center_dot}cm{sup {minus}2} in our apparatus, and (3) to increase the Q=O interfacial width from its value of a few tens of microns on Earth to about a millimeter in orbit. New technologies described in this paper are under development for this experiment, which is in definition for Space Shuttle flight.

  10. Critical Systems Heuristics

    NASA Astrophysics Data System (ADS)

    Ulrich, Werner; Reynolds, Martin

    Critical systems heuristics (CSH) is a framework for reflective professional practice organised around the central tool of boundary critique. This paper, written jointly by the original developer, Werner Ulrich, and Martin Reynolds, an experienced practitioner of CSH, offers a systematic introduction to the idea and use of boundary critique. Its core concepts are explained in detail and their use is illustrated by means of two case studies from the domain of environmental planning and management. A particular focus is on working constructively with tensions between opposing perspectives as they arise in many situations of professional intervention. These include tensions such as ‘situation' versus ‘system', ‘is' versus ‘ought' judgements, concerns of ‘those involved' versus ‘those affected but not involved', stakeholders' ‘stakes' versus ‘stakeholding issues', and others. Accordingly, boundary critique is presented as a participatory process of unfolding and questioning boundary judgements rather than as an expert-driven process of boundary setting. The paper concludes with a discussion of some essential skills and considerations regarding the practice of boundary critique.

  11. T-Shaped Frame Critical and Post-Critical Analysis

    NASA Astrophysics Data System (ADS)

    Doicheva, Albena

    2016-03-01

    The paper shows solution of a T-shaped frame, strength- ened with two linear springs, regarding critical and post-critical analysis. The solution is exact using the Euler elastic approach and the frame of reference, originated in the point of column axis inflexion. The derived Numerical results show the effect of the springs strengthening for the crit- ical and the post-critical system behaviour. The influence of the geometry change is analyzed, as well.

  12. Healthcare Disparities in Critical Illness

    PubMed Central

    Soto, Graciela J.; Martin, Greg S.; Gong, Michelle Ng

    2013-01-01

    Objective To summarize the current literature on racial and gender disparities in critical care and the mechanisms underlying these disparities in the course of acute critical illness. Data Sources MEDLINE search on the published literature addressing racial, ethnic, or gender disparities in acute critical illness such as sepsis, acute lung injury, pneumonia, venous thromboembolism, and cardiac arrest. Study Selection Clinical studies that evaluated general critically ill patient populations in the United States as well as specific critical care conditions were reviewed with a focus on studies evaluating factors and contributors to health disparities. Data Extraction Study findings are presented according to their association with the incidence, clinical presentation, management, and outcomes in acute critical illness. Data Synthesis This review presents potential contributors for racial and gender disparities related to genetic susceptibility, comorbidities, preventive health services, socioeconomic factors, cultural differences, and access to care. The data is organized along the course of acute critical illness. Conclusions The literature to date shows that disparities in critical care are most likely multifactorial involving individual, community, and hospital-level factors at several points in the continuum of acute critical illness. The data presented identify potential targets as interventions to reduce disparities in critical care and future avenues for research. PMID:24121467

  13. The Liver in Critical Illness.

    PubMed

    Damm, Tessa W; Kramer, David J

    2016-07-01

    Caring for critically ill patients with acute and/or chronic liver dysfunction poses a unique challenge. Proper resuscitation and early consideration for transfer to liver transplant centers have resulted in improved outcomes. Liver support devices and cellular models have not yet shown mortality benefit, but they hold promise in the critical care of patients with liver disease. This article reviews pertinent anatomic and physiologic considerations of the liver in critical illness, followed by a selective review of associated organ dysfunction. PMID:27339681

  14. Critical Viscosity of Xenon investigators

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Dr. Dr. Robert F. Berg (right), principal investigator and Dr. Micheal R. Moldover (left), co-investigator, for the Critical Viscosity of Xenon (CVX/CVX-2) experiment. They are with the National Institutes of Standards and Technology, Gaithersburg, MD. The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. Although it does not easily combine with other chemicals, its viscosity at the critical point can be used as a model for a range of chemicals.

  15. Sharpening your critical thinking skills.

    PubMed

    Kyzer, S P

    1996-01-01

    In the current environment of constant and rapid change in health care, critical thinking is essential. Both personal ability to think critically and a willingness to do so are involved and are related to the individual and to the organization in which the individual works. Knowledge, experience, attitudes, thinking strategies, skills, and an organizational culture that values critical thinking are essential factors in the development and practice of those skills. There is no magic solution. There must be a commitment by all levels of the organization to develop and use the principles and skills of critical thinking. PMID:9110811

  16. Sharpening your critical thinking skills.

    PubMed

    Kyzer, S P

    1996-01-01

    In the current environment of constant and rapid change in health care, critical thinking is essential. Both personal ability to think critically and a willingness to do so are involved and are related to the individual and to the organization in which the individual works. Knowledge, experience, attitudes, thinking strategies, skills, and an organizational culture that values critical thinking are essential factors in the development and practice of those skills. There is no magic solution. There must be a commitment by all levels of the organization to develop and use the principles and skills of critical thinking.

  17. Discipline-Based Art Education: Its Criticisms and Its Critics.

    ERIC Educational Resources Information Center

    Eisner, Elliot W.

    1988-01-01

    Discusses the criticisms of discipline-based art education published in the March 1988 issue of "Art Education." Responds to the arguments of Peter London, Helen Muth, Norma K. Pittard, and Karen Hamblen. States that art education would be better served if the energy devoted to criticism was directed toward constructive ends. (GEA)

  18. A Critical "Critical Inquiry" Proposition in Health and Physical Education

    ERIC Educational Resources Information Center

    Leahy, Deana; O'Flynn, Gabrielle; Wright, Jan

    2013-01-01

    A critical inquiry approach is one of five key characteristics that have shaped the development of the new Australian Curriculum: Health and Physical Education (AC: HPE). However, what this means is open to interpretation. In the various documents leading to the consultation draft AC: HPE and in this document itself, critical inquiry is used in…

  19. Do Critical Thinking Exercises Improve Critical Thinking Skills?

    ERIC Educational Resources Information Center

    Cotter, Ellen M.; Tally, Carrie Sacco

    2009-01-01

    Although textbooks routinely include exercises to improve critical thinking skills, the effectiveness of these exercises has not been closely examined. Additionally, the connection between critical thinking skills and formal operational thought is also relatively understudied. In the study reported here, college students completed measures of…

  20. How Critical Is Critical Thinking? FACTC Focus, 2010

    ERIC Educational Resources Information Center

    Doerr, Mark, Ed.

    2010-01-01

    "FACTC Focus" is a publication of Faculty Association of Community and Technical Colleges (FACTC) with the purpose of presenting diverse views on faculty issues. Included in this issue are: (1) LOL: The Easy ROUTE TO Critical Thinking (Barbara B. Parsons); (2) Critical Thinking: We Know It When We (Don't) See It (Jared Anthony); (3) Critical…

  1. Critical market crashes

    NASA Astrophysics Data System (ADS)

    Sornette, D.

    2003-04-01

    patterns have been documented for essentially all crashes on developed as well as emergent stock markets, on currency markets, on company stocks, and so on. We review this discovery at length and demonstrate how to use this insight and the detailed predictions obtained from these models to forecast crashes. For this, we review the major crashes of the past that occurred on the major stock markets of the planet and describe the empirical evidence of the universal nature of the critical log-periodic precursory signature of crashes. The concept of an “anti-bubble” is also summarized, with the Japanese collapse from the beginning of 1991 to present, taken as a prominent example. A prediction issued and advertised in January 1999 has been until recently born out with remarkable precision, predicting correctly several changes of trends, a feat notoriously difficult using standard techniques of economic forecasting. We also summarize a very recent analysis the behavior of the U.S. S&P500 index from 1996 to August 2002 and the forecast for the two following years. We conclude by presenting our view of the organization of financial markets.

  2. Scrutiny of Critical Thinking Concept

    ERIC Educational Resources Information Center

    Atabaki, Ali Mohammad Siahi; Keshtiaray, Narges; Yarmohammadian, Mohammad H.

    2015-01-01

    Learning critical thinking skills are the goal of educational systems so the term "critical thinking" (CT) is frequently found in educational policy documents. Despite this frequency, however, precise understandings among teachers of what CT really means do not exit. The present study is designed to answer the following question. We can…

  3. Understanding Friendship between Critical Friends

    ERIC Educational Resources Information Center

    Gibbs, Paul; Angelides, Panayiotis

    2008-01-01

    This conceptual article discusses the issue of friendship implied by the term "critical friends". Our argument relates to the generalized use of the term "friendship" and the assumptions that it may carry compared with the actuality of the roles played by critical friends. We attempt to build a more precise definition of friendship which we…

  4. Willa Cather as Drama Critic.

    ERIC Educational Resources Information Center

    Jensen, Marvin D.

    Although Willa Cather is known primarily for her short fiction and novels, she began her writing career as a literary and drama critic while still a student at the University of Nebraska. Her writing experience with the university literary periodical led her to become the drama critic for the "Nebraska State Journal," and later for the "Lincoln…

  5. Critical Thinking in Physical Education

    ERIC Educational Resources Information Center

    Humphries, Charlotte

    2014-01-01

    Changes in American education require that teachers are evaluated more often, and expectations increasingly include teaching to develop critical thinking skills. This article uses Bloom's taxonomy in describing ways physical educators can include critical thinking in their lessons, both to enhance their teaching and to meet expectations of…

  6. Critical Issues Facing School Principals

    ERIC Educational Resources Information Center

    Styron, Ronald A., Jr.; Styron, Jennifer L.

    2011-01-01

    The purpose of this study was to further extend research initially conducted in 2003 pertaining to the critical issues K-12 principals address on a daily basis. The study involved surveying school principals within the state of Mississippi to discover the critical issues they identified, the significance level of these issues, and the rationale…

  7. Critical thinking in physics education

    NASA Astrophysics Data System (ADS)

    Sadidi, Farahnaz

    2016-07-01

    We agree that training the next generation of leaders of the society, who have the ability to think critically and form a better judgment is an important goal. It is a long-standing concern of Educators and a long-term desire of teachers to establish a method in order to teach to think critically. To this end, many questions arise on three central aspects: the definition, the evaluation and the design of the course: What is Critical Thinking? How can we define Critical Thinking? How can we evaluate Critical Thinking? Therefore, we want to implement Critical Thinking in physics education. How can we teach for Critical Thinking in physics? What should the course syllabus and materials be? We present examples from classical physics and give perspectives for astro-particle physics. The main aim of this paper is to answer the questions and provide teachers with the opportunity to change their classroom to an active one, in which students are encouraged to ask questions and learn to reach a good judgment. Key words: Critical Thinking, evaluation, judgment, design of the course.

  8. Continuous-time adaptive critics.

    PubMed

    Hanselmann, Thomas; Noakes, Lyle; Zaknich, Anthony

    2007-05-01

    A continuous-time formulation of an adaptive critic design (ACD) is investigated. Connections to the discrete case are made, where backpropagation through time (BPTT) and real-time recurrent learning (RTRL) are prevalent. Practical benefits are that this framework fits in well with plant descriptions given by differential equations and that any standard integration routine with adaptive step-size does an adaptive sampling for free. A second-order actor adaptation using Newton's method is established for fast actor convergence for a general plant and critic. Also, a fast critic update for concurrent actor-critic training is introduced to immediately apply necessary adjustments of critic parameters induced by actor updates to keep the Bellman optimality correct to first-order approximation after actor changes. Thus, critic and actor updates may be performed at the same time until some substantial error build up in the Bellman optimality or temporal difference equation, when a traditional critic training needs to be performed and then another interval of concurrent actor-critic training may resume. PMID:17526332

  9. A Place for Critical Literacy

    ERIC Educational Resources Information Center

    Beck, Ann S.

    2005-01-01

    The critical literacy classroom is characterized by an emphasis on students' voices and on dialogue as a tool with which students reflect on and construct meanings from texts and discourses. Is it appropriate, however, to teach critical literacy in settings such as penal institutions where student voices are deliberately discouraged and silenced?…

  10. Traditional Literacy and Critical Thinking

    ERIC Educational Resources Information Center

    Dando, Priscille

    2016-01-01

    How school librarians focus on activating critical thinking through traditional literacy development can proactively set the stage for the deep thinking that occurs in all literacy development. The critical-thinking skills students build while becoming accomplished readers and writers provide the foundation for learning in a variety of…

  11. Harnessing Critical Incidents for Learning

    ERIC Educational Resources Information Center

    Patahuddin, Sitti Maesuri; Lowrie, Tom

    2015-01-01

    A critical incident is a situation or event that holds significance for learning, both for the students and teachers. This paper presents four examples of critical incidents from a Year 7 teacher's lesson excerpts in Indonesia involving teaching of fractions, to show how they shaped classroom situation, brought forward elements of conflict, and…

  12. Quantifying Learning in Critical Thinking

    ERIC Educational Resources Information Center

    Fliegel, Richard; Holland, John

    2013-01-01

    This article describes a three-year study assessing change in critical thinking demonstrated in essays written for regular class assignments. A rubric was designed and scorers trained to assess critical thinking holistically without knowledge of the writing prompt or author's status. The longitudinal improvement in scores earned by freshmen…

  13. Cabbage Worms and Critical Thinking.

    ERIC Educational Resources Information Center

    Braswell, Patricia

    1993-01-01

    Argues that an approach to composition instruction that emphasizes critical thinking skills produces a more analytical writer. Describes a school project that examined research on critical thinking, implemented changes in the teaching of thinking and composition, and assessed student learning. (HB)

  14. Critical Pedagogy in Health Education

    ERIC Educational Resources Information Center

    Matthews, Catherine

    2014-01-01

    Objective: This review investigated how the three-phase model of critical pedagogy, based on the writings of Paulo Freire, can be put into practice in health education. Design: The study considers literature related to the fields of health education, health promotion and critical pedagogy. Setting: The study is a scholarly review completed as part…

  15. Teaching Students to Think Critically

    ERIC Educational Resources Information Center

    Black, Susan

    2005-01-01

    In this article, the author stresses that teachers need to teach their students to think critically and to reason their way. One prerequisite for teaching critical thinking is a classroom climate of high expectations, teacher warmth and encouragement, and pleasant physical surroundings. Schools should see to it that students become progressively…

  16. Education Studies: Issues & Critical Perspectives

    ERIC Educational Resources Information Center

    Kassem, Derek; Mufti, Emmanuel; Robinson, John

    2006-01-01

    This major text for Education Studies students provides a critical account of key issues in education today. The text features: (1) A critical analysis of key issues in Education Studies to encourage students' thinking about education in the broadest terms; (2) Themed sections with introductions to link the issues discussed in each chapter; (3)…

  17. Critical Thinking: Schemata vs. Skills.

    ERIC Educational Resources Information Center

    Brandhorst, Allan R.

    1989-01-01

    Refutes the idea that critical thinking is not a skill by analyzing it from the phenomenological perspective of Edmund Husserl, and from the hermeneutic perspective of Martin Heidegger. Develops the thesis that critical thinking is a restructuring of schemata. Addresses the problem of attention or student engagement. (LS)

  18. Critical appraisal of clinical guidelines.

    PubMed

    Netsch, Debra S; Kluesner, Jean A

    2010-01-01

    Utilization of clinical guidelines is gaining in popularity due to their significant impact on clinical practice. While a plethora of guidelines exist, many are lacking in quality, based on current critical appraisal standards. It then becomes necessary for the end users of the guidelines to adopt or develop those that are deemed adequate for implementation. This often requires that users possess critical appraisal skills as they become proficient in discerning between guidelines of varying quality. This article provides direction and tools to support the critical appraisal process in the adoption of clinical guidelines. PMID:20838314

  19. Adaptive critics for dynamic optimization.

    PubMed

    Kulkarni, Raghavendra V; Venayagamoorthy, Ganesh Kumar

    2010-06-01

    A novel action-dependent adaptive critic design (ACD) is developed for dynamic optimization. The proposed combination of a particle swarm optimization-based actor and a neural network critic is demonstrated through dynamic sleep scheduling of wireless sensor motes for wildlife monitoring. The objective of the sleep scheduler is to dynamically adapt the sleep duration to node's battery capacity and movement pattern of animals in its environment in order to obtain snapshots of the animal on its trajectory uniformly. Simulation results show that the sleep time of the node determined by the actor critic yields superior quality of sensory data acquisition and enhanced node longevity. PMID:20223635

  20. Critical behavior of gravitating sphalerons

    NASA Astrophysics Data System (ADS)

    Millward, R. Steven; Hirschmann, Eric W.

    2003-07-01

    We examine the gravitational collapse of sphaleron type configurations in the Einstein-Yang-Mills-Higgs theory. Working in spherical symmetry, we investigate the critical behavior in this model. We provide evidence that for various initial configurations, there can be three different critical transitions between possible end states with different critical solutions sitting on the threshold between these outcomes. In addition, we show that within the dispersive and black hole regimes there are new possible end states: namely, a stable, regular sphaleron and a stable, hairy black hole.

  1. HELIOS Critical Design Review: Reliability

    NASA Technical Reports Server (NTRS)

    Benoehr, H. C.; Herholz, J.; Prem, H.; Mann, D.; Reichert, L.; Rupp, W.; Campbell, D.; Boettger, H.; Zerwes, G.; Kurvin, C.

    1972-01-01

    This paper presents Helios Critical Design Review Reliability form October 16-20, 1972. The topics include: 1) Reliability Requirement; 2) Reliability Apportionment; 3) Failure Rates; 4) Reliability Assessment; 5) Reliability Block Diagram; and 5) Reliability Information Sheet.

  2. The critics return to flight.

    PubMed

    Jones, Thomas D

    2005-08-01

    A former astronaut justifies human space exploration and provides a rebuttal to criticism of continued exploration. The discussion includes examples of skeptics' arguments and examples of NASA achievements that have had direct economic and social impacts on the United States.

  3. Coping with criticism and praise.

    PubMed

    Esdale, Lynn; Jahoda, Andrew; Pert, Carol

    2015-05-01

    Through experiencing stigma and discrimination, people with intellectual disability may become more sensitive to criticism from others and be less likely to believe praise. This study compared how people with and without intellectual disability viewed praise and criticism, using a vignette task developed for the study. Participants were asked to imagine someone saying something praiseworthy or critical and were then asked about their emotions, beliefs, and thoughts. People with intellectual disability were more likely to believe and be distressed by criticism. Contrary to predictions, this group were also more likely to believe praise and experience positive affect. The results suggest that the self-perceptions of people with intellectual disabilities is more dynamic and reliant on the views of others.

  4. Critical Barriers to Science Learning

    ERIC Educational Resources Information Center

    Hawkins, David

    1978-01-01

    The author illustrates and discusses some critical barrier phenomena, such as the optics of mirrors and heat and cold, which most people have difficulty extending beyond an everyday understanding. (Author/MA)

  5. Critical scattering in polymer melts

    SciTech Connect

    Bates, F.S.; Hartney, M.A.; Wignall, G.D.

    1985-10-01

    Critical phenomena in two classes of polymer melts have been examined by small-angle neutron scattering (SANS); single component block polymers which undergo an order-disorder phase transition, and binary polymer mixtures which exhibit classical liquid-liquid phase separation behavior. A model set of 1,4-polybutadiene-1,2-polybutadiene diblock copolymers containing perdeuterated 1,4-polybutadiene blocks were investigated by SANS in the disordered state. The SANS spectra exhibit a peak in the scattering intensity which diverges at the ordering transition, in close agreement with mean-field theory. Binary blends of perdeuterated and protonated 1,4-polybutadiene homopolymers have been found to form regular solutions characterized by an upper critical solution temperature (UCST). Near the critical point, these mixtures exhibit classical critical scattering as measured by SANS. The second set of results raises serious questions regarding the widely held assumption that deuterated and protonated polymers form ideal mixtures.

  6. Critical Theory in Historical Perspective.

    ERIC Educational Resources Information Center

    Hardt, Hanno

    1986-01-01

    Reviews two books by Martin Jay on the intellectual history of Western Marxism and critical theory "in exile" that detail the complex foundations of an ideological critique of culture and society and evaluates their meaning for communications scholarship. (JD)

  7. Nonadditivity of critical Casimir forces.

    PubMed

    Paladugu, Sathyanarayana; Callegari, Agnese; Tuna, Yazgan; Barth, Lukas; Dietrich, Siegfried; Gambassi, Andrea; Volpe, Giovanni

    2016-01-01

    In soft condensed matter physics, effective interactions often emerge due to the spatial confinement of fluctuating fields. For instance, microscopic particles dissolved in a binary liquid mixture are subject to critical Casimir forces whenever their surfaces confine the thermal fluctuations of the order parameter of the solvent close to its critical demixing point. These forces are theoretically predicted to be nonadditive on the scale set by the bulk correlation length of the fluctuations. Here we provide direct experimental evidence of this fact by reporting the measurement of the associated many-body forces. We consider three colloidal particles in optical traps and observe that the critical Casimir force exerted on one of them by the other two differs from the sum of the forces they exert separately. This three-body effect depends sensitively on the distance from the critical point and on the chemical functionalisation of the colloid surfaces. PMID:27097797

  8. Psychoanalytic Criticism and Teaching Shakespeare.

    ERIC Educational Resources Information Center

    Wheeler, Richard P.

    1987-01-01

    Presents a brief overview of previous psychoanalytically based theories of Shakespeare's plays, particularly "Hamlet," and defends the notion of introducing undergraduates to psychoanalytically based criticism because of the insights it may give students into their own lives. (JC)

  9. Television Criticism: A Multifarious Approach.

    ERIC Educational Resources Information Center

    Oseguera, A. Anthony

    Recognizing the need for a multifarious approach to television, this paper provides the reader with the following multidimensional approaches to television criticism: rhetorical, dramatic, literary, cinematic, content analysis, myth, linguistics, semiotics, phenomenalism, phenomenology, interpersonal communication, public relations, image,…

  10. Nonadditivity of critical Casimir forces

    PubMed Central

    Paladugu, Sathyanarayana; Callegari, Agnese; Tuna, Yazgan; Barth, Lukas; Dietrich, Siegfried; Gambassi, Andrea; Volpe, Giovanni

    2016-01-01

    In soft condensed matter physics, effective interactions often emerge due to the spatial confinement of fluctuating fields. For instance, microscopic particles dissolved in a binary liquid mixture are subject to critical Casimir forces whenever their surfaces confine the thermal fluctuations of the order parameter of the solvent close to its critical demixing point. These forces are theoretically predicted to be nonadditive on the scale set by the bulk correlation length of the fluctuations. Here we provide direct experimental evidence of this fact by reporting the measurement of the associated many-body forces. We consider three colloidal particles in optical traps and observe that the critical Casimir force exerted on one of them by the other two differs from the sum of the forces they exert separately. This three-body effect depends sensitively on the distance from the critical point and on the chemical functionalisation of the colloid surfaces. PMID:27097797

  11. Interpretative reports and critical values.

    PubMed

    Piva, Elisa; Plebani, Mario

    2009-06-01

    In the clinical laboratory to allow an effective testing process, post-analytical activity can have two goals in trying to improve patient safety: result interpretation and communication of critical values. Both are important issues, and their success requires a cooperative effort. Misinterpretation of laboratory test results or ineffectiveness in their notification can lead to diagnostic errors or errors in identifying patient critical conditions. With the awareness that the incorrect interpretation of tests and the breakdown in the communication of critical values are preventable errors, laboratorians should make every effort to prevent the types of errors that potentially harm patients. In order to improve the reliability of laboratories, we attempt to explain how interpretative reporting and automated notification of critical values can be used to reduce errors. Clinical laboratories can therefore work to improve clinical effectiveness, without forgetting that everything should be designed to provide the best outcomes for patients.

  12. Identity Politics and Critical Pedagogy.

    ERIC Educational Resources Information Center

    Bromley, Hank

    1989-01-01

    This essay investigates what identity politics may have to contribute to the reformation of Marxist theories of education through considering how it would theorize the practice of explicitly critical pedagogy. (IAH)

  13. Autoclave nuclear criticality safety analysis

    SciTech Connect

    D`Aquila, D.M.; Tayloe, R.W. Jr.

    1991-12-31

    Steam-heated autoclaves are used in gaseous diffusion uranium enrichment plants to heat large cylinders of UF{sub 6}. Nuclear criticality safety for these autoclaves is evaluated. To enhance criticality safety, systems are incorporated into the design of autoclaves to limit the amount of water present. These safety systems also increase the likelihood that any UF{sub 6} inadvertently released from a cylinder into an autoclave is not released to the environment. Up to 140 pounds of water can be held up in large autoclaves. This mass of water is sufficient to support a nuclear criticality when optimally combined with 125 pounds of UF{sub 6} enriched to 5 percent U{sup 235}. However, water in autoclaves is widely dispersed as condensed droplets and vapor, and is extremely unlikely to form a critical configuration with released UF{sub 6}.

  14. Autism: a "critical period" disorder?

    PubMed

    LeBlanc, Jocelyn J; Fagiolini, Michela

    2011-01-01

    Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I) neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits.

  15. Critical health literacy: a review and critical analysis.

    PubMed

    Chinn, Deborah

    2011-07-01

    Though there has been a considerable expansion of interest in the health literacy concept worldwide, there has also been criticism that this concept has been poorly defined, that it stretches the idea of "literacy" to an indefensible extent and more specifically, that it adds little to the existing concerns and intervention approaches of the better established discipline of health promotion. This paper takes as a starting point the expanded model of health literacy advanced by Nutbeam (2000) and addresses these concerns by interrogating the concept of "critical health literacy" in order to draw conclusions about its utility for advancing the health of individuals and communities. The constituent domains of critical health literacy are identified; namely information appraisal, understanding the social determinants of health, and collective action, and as far as possible each are clearly delineated, with links to related concepts made explicit. The paper concludes that an appreciation of work undertaken in a range of different disciplines, such as media studies, medical sociology, and evidence-based medicine can enhance our understanding of the critical health literacy construct and help us understand its usefulness as a social asset which helps individuals towards a critical engagement with health information. There is some evidence that aspects of critical health literacy have indeed been found to be a resource for better health outcomes, but more research is needed in this area, both to develop quantitative and qualitative approaches to evaluating health literacy skills, and to offer convincing evidence that investment in programmes designed to enhance critical health literacy are worthwhile.

  16. Solid-gas critical flow

    SciTech Connect

    Gidaspow, D.; Syamlal, M.

    1985-01-01

    Maximum solid-gas transport rates have been computed using several hydrodynamic models. In the limit of zero gas density, the critical velocity equals the square root of a compressibility modulus of the powder divided by its density. Compressibility waves move with this velocity through the powder. Part II of this paper deals with homogeneous critical powder flow for which a useful expression for maximum flow has been derived and compared to an experiment from the literature.

  17. Lecture notes for criticality safety

    SciTech Connect

    Fullwood, R.

    1992-03-01

    These lecture notes for criticality safety are prepared for the training of Department of Energy supervisory, project management, and administrative staff. Technical training and basic mathematics are assumed. The notes are designed for a two-day course, taught by two lecturers. Video tapes may be used at the options of the instructors. The notes provide all the materials that are necessary but outside reading will assist in the fullest understanding. The course begins with a nuclear physics overview. The reader is led from the macroscopic world into the microscopic world of atoms and the elementary particles that constitute atoms. The particles, their masses and sizes and properties associated with radioactive decay and fission are introduced along with Einstein's mass-energy equivalence. Radioactive decay, nuclear reactions, radiation penetration, shielding and health-effects are discussed to understand protection in case of a criticality accident. Fission, the fission products, particles and energy released are presented to appreciate the dangers of criticality. Nuclear cross sections are introduced to understand the effectiveness of slow neutrons to produce fission. Chain reactors are presented as an economy; effective use of the neutrons from fission leads to more fission resulting in a power reactor or a criticality excursion. The six-factor formula is presented for managing the neutron budget. This leads to concepts of material and geometric buckling which are used in simple calculations to assure safety from criticality. Experimental measurements and computer code calculations of criticality are discussed. To emphasize the reality, historical criticality accidents are presented in a table with major ones discussed to provide lessons-learned. Finally, standards, NRC guides and regulations, and DOE orders relating to criticality protection are presented.

  18. Lecture notes for criticality safety

    SciTech Connect

    Fullwood, R.

    1992-03-01

    These lecture notes for criticality safety are prepared for the training of Department of Energy supervisory, project management, and administrative staff. Technical training and basic mathematics are assumed. The notes are designed for a two-day course, taught by two lecturers. Video tapes may be used at the options of the instructors. The notes provide all the materials that are necessary but outside reading will assist in the fullest understanding. The course begins with a nuclear physics overview. The reader is led from the macroscopic world into the microscopic world of atoms and the elementary particles that constitute atoms. The particles, their masses and sizes and properties associated with radioactive decay and fission are introduced along with Einstein`s mass-energy equivalence. Radioactive decay, nuclear reactions, radiation penetration, shielding and health-effects are discussed to understand protection in case of a criticality accident. Fission, the fission products, particles and energy released are presented to appreciate the dangers of criticality. Nuclear cross sections are introduced to understand the effectiveness of slow neutrons to produce fission. Chain reactors are presented as an economy; effective use of the neutrons from fission leads to more fission resulting in a power reactor or a criticality excursion. The six-factor formula is presented for managing the neutron budget. This leads to concepts of material and geometric buckling which are used in simple calculations to assure safety from criticality. Experimental measurements and computer code calculations of criticality are discussed. To emphasize the reality, historical criticality accidents are presented in a table with major ones discussed to provide lessons-learned. Finally, standards, NRC guides and regulations, and DOE orders relating to criticality protection are presented.

  19. Training in critical care echocardiography

    PubMed Central

    2011-01-01

    Echocardiography is useful for the diagnosis and management of hemodynamic failure in the intensive care unit so that competence in some elements of echocardiography is a core skill of the critical care specialist. An important issue is how to provide training to intensivists so that they are competent in the field. This article will review issues related to training in critical care echocardiography. PMID:21906268

  20. Brane worlds in critical gravity

    NASA Astrophysics Data System (ADS)

    Chen, Feng-Wei; Liu, Yu-Xiao; Zhong, Yuan; Wang, Yong-Qiang; Wu, Shao-Feng

    2013-11-01

    Recently, Lü and Pope proposed critical gravities in [Phys. Rev. Lett. 106, 181302 (2011)]. In this paper we construct analytic brane solutions in critical gravity with matter. The Gibbons-Hawking surface term and junction condition are investigated, and the thin and thick brane solutions are obtained. All these branes are embedded in five-dimensional anti-de Sitter spacetimes. Our solutions are stable against scalar perturbations, and the zero modes of scalar perturbations cannot be localized on the branes.

  1. Critical realism and the dialectic.

    PubMed

    Roberts, J M

    2001-12-01

    A prominent strand within both sociological and social theory has been concerned to develop a 'systems approach' with which to explore social life. One of the most original contributions to a systems approach has arisen within critical realism. In particular critical realism demonstrates that it is possible to abstract the causal powers of different objects of analysis to examine their interaction within concrete and contingent 'open systems'. The recent dialectical turn of critical realism develops this systems approach in a much more rigorous manner. However, in this paper I argue that the (dialectical) critical realist mode of abstraction ultimately fails to embed concepts and categories internally within the specific ideological and historical forms of social relations. Or rather, critical realists do not seek to develop concepts that reflect the self-movement of a historical and contradictory essence. This self-movement is what I prefer to call a 'system'. Consequently critical realists are led to separate method from system in theory construction and such a separation leads to a problematic dualist mode of theorizing. I make these observations from a Hegelian-Marxist position. PMID:11853063

  2. Rethinking regulations for disposal criticality

    SciTech Connect

    Scott, M.; Doering, T.

    1997-08-01

    This paper provides the basis for the position that the current U.S. Nuclear Regulatory Commission (NRC) criticality regulation is in need of revision to address problems in implementing it for the postclosure period in a geologic high-level waste repository. The authors believe that the applicant for such a facility should be able to demonstrate that postulated postclosure criticality events will not cause unacceptable risk of deleterious effects on public health and safety. In addition, the applicant should be expected to take practical and feasible measures to reduce the probability of a criticality occurring, even if (as expected) the consequences of such a criticality for repository performance and public health and safety would be negligible. This approach, while recognizing the probabilistic nature of analyses of events and conditions in the distant future, is also arguably consistent with the defense in depth concept that has been successfully applied to nuclear reactor regulation. The authors believe regulations for postclosure criticality control should support this dual approach, rather than require a deterministic prohibition of criticality as does the current rule. The existing rule seems appropriate for the preclosure period, as long as it is clearly specified to apply only to that period.

  3. Psychopharmacology in pediatric critical care.

    PubMed

    Stoddard, Frederick J; Usher, Craigan T; Abrams, Annah N

    2006-07-01

    Psychopharmacologic treatment in pediatric critical care requires a careful child or adolescent psychiatric evaluation, including a thorough review of the history of present illness or injury, any current or pre-existing psychiatric disorder, past history, and laboratory studies. Although there is limited evidence to guide psychopharmacologic practice in this setting, psychopharmacologic treatment is increasing in critical care, with known indications for treatment, benefits, and risks; initial dosing guidelines; and best practices. Treatment is guided by the knowledge bases in pediatric physiology, psycho-pharmacology, and treatment of critically ill adults. Pharmacologic considerations include pharmacokinetic and pharmcodynamic aspects of specific drugs and drug classes, in particular elimination half-life, developmental considerations, drug interactions, and adverse effects. Evaluation and management of pain is a key initial step, as pain may mimic psychiatric symptoms and its effective treatment can ameliorate them. Patient comfort and safety are primary objectives for children who are acutely ill and who will survive and for those who will not. Judicious use of psychopharmacolgic agents in pediatric critical care using the limited but growing evidence base and a clinical best practices collaborative approach can reduce anxiety,sadness, disorientation, and agitation; improve analgesia; and save lives of children who are suicidal or delirious. In addition to pain, other disorders or indications for psychopharmacologic treatment are affective disorders;PTSD; post-suicide attempt patients; disruptive behavior disorders (especially ADHD); and adjustment, developmental, and substance use disorders. Treating children who are critically ill with psychotropic drugs is an integral component of comprehensive pediatric critical care in relieving pain and delirium; reducing inattention or agitation or aggressive behavior;relieving acute stress, anxiety, or depression; and

  4. Superstatistics and renewal critical events

    NASA Astrophysics Data System (ADS)

    Paradisi, Paolo; Cesari, Rita; Grigolini, Paolo

    2009-09-01

    An approach to intermittent systems based on renewal processes is reviewed. The Waiting Times (WTs) between events are the main variables of interest in intermittent systems. A crucial role is played by the class of critical events, characterized by Non-Poisson statistics and non-exponential WT distribution. A particular important case is given by WT distributions with power tail. Critical events play a crucial role in the behavior of a property known as Renewal Aging. Focusing on the role of critical events, the relation between superstatistics and non-homogeneous Poisson processes is discussed, and the role of Renewal Aging is illustrated by comparing a Non-Poisson model with a Poisson one, both of them modulated by a periodic forcing. It is shown that the analysis of Renewal Aging is sensitive to the presence of critical events and that this property can be exploited to detect Non-Poisson statistics in a time series. As a consequence, it is claimed that, apart from the characterization of superstatistical features such as the distribution of the intensive parameter or the separation of the time scales, the Renewal Aging property can give some effort to better determine the role of Non-Poisson critical events in intermittent systems.

  5. Criticism and the Teaching of Literature.

    ERIC Educational Resources Information Center

    Miller, James E., Jr., Ed.

    1965-01-01

    Articles contained in this publication are (1) "Criticism in Teaching Literature" by Wayne Booth; (2) "Criticism and Literature: A Reply" (to Booth's article) by Frederick J. Hoffman; (3) "Criticism in Context" by Helen C. White; (4) "Formalist Criticism and Shakespeare" by Kester Svendsen; (5) "Grammar, History, and Criticism" by Kenneth S.…

  6. Critical and Alternative Directions in Applied Linguistics

    ERIC Educational Resources Information Center

    Pennycook, Alastair

    2010-01-01

    Critical directions in applied linguistics can be understood in various ways. The term "critical" as it has been used in "critical applied linguistics," "critical discourse analysis," "critical literacy" and so forth, is now embedded as part of applied linguistic work, adding an overt focus on questions of power and inequality to discourse…

  7. Critical gravity in four dimensions.

    PubMed

    Lü, H; Pope, C N

    2011-05-01

    We study four-dimensional gravity theories that are rendered renormalizable by the inclusion of curvature-squared terms to the usual Einstein action with a cosmological constant. By choosing the parameters appropriately, the massive scalar mode can be eliminated and the massive spin-2 mode can become massless. This "critical" theory may be viewed as a four-dimensional analogue of chiral topologically massive gravity, or of critical "new massive gravity" with a cosmological constant, in three dimensions. We find that the on-shell energy for the remaining massless gravitons vanishes. There are also logarithmic spin-2 modes, which have positive energy. The mass and entropy of standard Schwarzschild-type black holes vanish. The critical theory might provide a consistent toy model for quantum gravity in four dimensions. PMID:21635082

  8. Teamwork in obstetric critical care

    PubMed Central

    Guise, Jeanne-Marie; Segel, Sally

    2016-01-01

    Whether seeing a patient in the ambulatory clinic environment, performing a delivery or managing a critically ill patient, obstetric care is a team activity. Failures in teamwork and communication are among the leading causes of adverse obstetric events, accounting for over 70% of sentinel events according to the Joint Commission. Effective, efficient and safe care requires good teamwork. Although nurses, doctors and healthcare staff who work in critical care environments are extremely well trained and competent medically, they have not traditionally been trained in how to work well as part of a team. Given the complexity and acuity of critical care medicine, which often relies on more than one medical team, teamwork skills are essential. This chapter discusses the history and importance of teamwork in high-reliability fields, reviews key concepts and skills in teamwork, and discusses approaches to training and working in teams. PMID:18701352

  9. Update in Critical Care 2015.

    PubMed

    Dres, Martin; Mancebo, Jordi; Curley, Gerard F

    2016-07-01

    This review documents important progress made in 2015 in the field of critical care. Significant advances in 2015 included further evidence for early implementation of low tidal volume ventilation as well as new insights into the role of open lung biopsy, diaphragmatic dysfunction, and a potential mechanism for ventilator-induced fibroproliferation. New therapies, including a novel low-flow extracorporeal CO2 removal technique and mesenchymal stem cell-derived microparticles, have also been studied. Several studies examining the role of improved diagnosis and prevention of ventilator-associated pneumonia also showed relevant results. This review examines articles published in the American Journal of Respiratory and Critical Care Medicine and other major journals that have made significant advances in the field of critical care in 2015. PMID:27367886

  10. Teamwork in obstetric critical care.

    PubMed

    Guise, Jeanne-Marie; Segel, Sally

    2008-10-01

    Whether seeing a patient in the ambulatory clinic environment, performing a delivery or managing a critically ill patient, obstetric care is a team activity. Failures in teamwork and communication are among the leading causes of adverse obstetric events, accounting for over 70% of sentinel events according to the Joint Commission. Effective, efficient and safe care requires good teamwork. Although nurses, doctors and healthcare staff who work in critical care environments are extremely well trained and competent medically, they have not traditionally been trained in how to work well as part of a team. Given the complexity and acuity of critical care medicine, which often relies on more than one medical team, teamwork skills are essential. This chapter discusses the history and importance of teamwork in high-reliability fields, reviews key concepts and skills in teamwork, and discusses approaches to training and working in teams.

  11. Critical neuroscience meets medical humanities.

    PubMed

    Slaby, Jan

    2015-06-01

    This programmatic theory paper sketches a conceptual framework that might inspire work in critical Medical Humanities. For this purpose, Kaushik Sunder Rajan's account of biocapital is revisited and discussed in relation to the perspective of a critical neuroscience. Critical neuroscience is an encompassing positioning towards the recent public prominence of the brain and brain-related practices, tools and discourses. The proposed analytical scheme has five focal nodes: capital, life, technoscience, (neoliberal) politics and subjectivity. A special emphasis will be placed on contemporary framings of subjectivity, as it is here where deep-reaching entanglements of personhood with scientific practice and discourse, medical and informational technologies, and economic formations are most evident. Notably, the emerging subject position of the 'prospective health consumer' will be discussed as it figures prominently in the terrain between neuroscience and other medico-scientific disciplines.

  12. A critical analysis of compliance.

    PubMed

    Murphy, N; Canales, M

    2001-09-01

    In nursing the word compliance has competing meanings. In order to understand these meanings, nursing literature was reviewed and a critical analysis of this concept was undertaken. This included an examination of how nursing was located in relation to the historical controversy surrounding the term compliance. The philosophy that undergirds this analysis is critical theory scholarship, which focuses on language as a vehicle for social control and domination. Literature was critically analyzed according to how nurse authors define the term compliance and the historical context in which the term was used. Analysis of the literature revealed three distinct categories: evaluative, rationalization, and acceptance. Each of these categories is described and the selection criteria identified. We recommend that, nurses intent on conducting future compliance research, consider emancipatory models for their investigations. PMID:11882216

  13. Critical Gravity in Four Dimensions

    SciTech Connect

    Lue, H.; Pope, C. N.

    2011-05-06

    We study four-dimensional gravity theories that are rendered renormalizable by the inclusion of curvature-squared terms to the usual Einstein action with a cosmological constant. By choosing the parameters appropriately, the massive scalar mode can be eliminated and the massive spin-2 mode can become massless. This ''critical'' theory may be viewed as a four-dimensional analogue of chiral topologically massive gravity, or of critical 'new massive gravity' with a cosmological constant, in three dimensions. We find that the on-shell energy for the remaining massless gravitons vanishes. There are also logarithmic spin-2 modes, which have positive energy. The mass and entropy of standard Schwarzschild-type black holes vanish. The critical theory might provide a consistent toy model for quantum gravity in four dimensions.

  14. Critical gravity in four dimensions.

    PubMed

    Lü, H; Pope, C N

    2011-05-01

    We study four-dimensional gravity theories that are rendered renormalizable by the inclusion of curvature-squared terms to the usual Einstein action with a cosmological constant. By choosing the parameters appropriately, the massive scalar mode can be eliminated and the massive spin-2 mode can become massless. This "critical" theory may be viewed as a four-dimensional analogue of chiral topologically massive gravity, or of critical "new massive gravity" with a cosmological constant, in three dimensions. We find that the on-shell energy for the remaining massless gravitons vanishes. There are also logarithmic spin-2 modes, which have positive energy. The mass and entropy of standard Schwarzschild-type black holes vanish. The critical theory might provide a consistent toy model for quantum gravity in four dimensions.

  15. Transmission of information at criticality

    NASA Astrophysics Data System (ADS)

    Luković, Mirko; Vanni, Fabio; Svenkeson, Adam; Grigolini, Paolo

    2014-12-01

    We study the problem of information transmission in complex cooperative systems to prove that adaptivity rather than diffusion is the main source of information transport at criticality. We adopt two different cooperative models, the two-dimensional Decision Making Model (DMM), and the one-dimensional Flock Model (FM) inspired by the cooperation between birds. The criticality-induced consensus is intermittently broken by the occurrence of moments of high susceptibility, which we call free-will states. We construct a network A based on the DMM and FM that is perturbed by a similar network B. Some units of A, called lookout birds, follow the directions of the mean field generated by B, while the rest are blind to B. When both networks are at criticality a small percentage of lookout birds establish the synchronization between B and A as a result of the nonergodic nature of the free-will state dynamics.

  16. Clinical review: Critical care transport and austere critical care

    PubMed Central

    Rice, David H; Kotti, George; Beninati, William

    2008-01-01

    The development of modern intensive care units (ICUs) has allowed the survival of patients with advanced illness and injury, although at a cost of substantial infrastructure. Natural disasters and military operations are two common situations that can create critically ill patients in an environment that is austere or has been rendered austere. This has driven the development of two related strategies to care for these casualties. Portable ICU capability can be rapidly established in the area of need, providing relatively advanced capability but limited capacity and sustainability. The other strategy is to rapidly evacuate critically ill and injured patients following their initial stabilization. This permits medical personnel in the austere location to focus resources on a larger number of less critical patients. It also permits the most vulnerable patients to receive care in an advanced center. This strategy requires careful planning to overcome the constraints of the transport environment. The optimal strategy has not been determined, but a combination of these two approaches has been used in recent disasters and military operations and is promising. The critical care delivered in an austere setting must be integrated with a long-term plan to provide follow-on care. PMID:18373882

  17. In Defense of a Liberal Education: Criticizing the Critical

    ERIC Educational Resources Information Center

    Attard, John

    2013-01-01

    In this article, the author reports on an awareness of controversial incidents on campuses around North America surrounding "politically correct" speech codes and thought control measures instituted at the behest of faculty and students of this ideological persuasion. It seems that critical theory is going beyond "critical…

  18. Critical Qualitative Research Reader. Critical Qualitative Research. Volume 2

    ERIC Educational Resources Information Center

    Steinberg, Shirley R., Ed.; Cannella, Gaile S., Ed.

    2012-01-01

    This volume of transformed research utilizes an activist approach to examine the notion that nothing is apolitical. Research projects themselves are critically examined for power orientations, even as they are used to address curricular problems and educational or societal issues. Philosophical perspectives that have facilitated an understanding…

  19. A Critical Review of the Critical Period Research.

    ERIC Educational Resources Information Center

    Scovel, Thomas

    2000-01-01

    Discusses how perspectives on the critical period hypothesis (CPH) have shifted over the last 20-20 years, because of the work of applied linguistics and other disciplines. Advises caution into translating CPH research into personal practice or public policy. (Author/VWL)

  20. PRECLOSURE CRITICALITY ANALYSIS PROCESS REPORT

    SciTech Connect

    A.E. Danise

    2004-10-25

    This report describes a process for performing preclosure criticality analyses for a repository at Yucca Mountain, Nevada. These analyses will be performed from the time of receipt of fissile material until permanent closure of the repository (preclosure period). The process describes how criticality safety analyses will be performed for various configurations of waste in or out of waste packages that could occur during preclosure as a result of normal operations or event sequences. The criticality safety analysis considers those event sequences resulting in unanticipated moderation, loss of neutron absorber, geometric changes, or administrative errors in waste form placement (loading) of the waste package. The report proposes a criticality analyses process for preclosure to allow a consistent transition from preclosure to postclosure, thereby possibly reducing potential cost increases and delays in licensing of Yucca Mountain. The proposed approach provides the advantage of using a parallel regulatory framework for evaluation of preclosure and postclosure performance and is consistent with the U.S. Nuclear Regulatory Commission's approach of supporting risk-informed, performance-based regulation for fuel cycle facilities, ''Yucca Mountain Review Plan, Final Report'', and 10 CFR Part 63. The criticality-related criteria for ensuring subcriticality are also described as well as which guidance documents will be utilized. Preclosure operations and facilities have significant similarities to existing facilities and operations currently regulated by the U.S. Nuclear Regulatory Commission; therefore, the design approach for preclosure criticality safety will be dictated by existing regulatory requirements while using a risk-informed approach with burnup credit for in-package operations.

  1. Cyberspace Policy For Critical Infrastructures

    NASA Astrophysics Data System (ADS)

    Wilkin, Dorsey; Raines, Richard; Williams, Paul; Hopkinson, Kenneth

    The first step in preparing any battlespace is to define the domain for attack and maneuver. The various military service components have directed authority to focus their efforts in specific domains of operations (e.g., naval operations are mainly in the maritime domain). However, cyberspace operations pose challenges because they span multiple operational domains. This paper focuses on U.S. cyberspace policy related to defending and exploiting critical infrastructure assets. Also, it examines the issues involved in delineating responsibility for U.S. defensive and offensive operations related to critical infrastructures.

  2. Critical Viscosity of Xenon team

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. The thermostat for CVX sits inside the white cylinder on a support structure (at left) that is placed inside a pressure canister. A similar canister (right) holds the electronics and control systems. The CVX-2 arrangement is identical. The principal investigator is Dr. Robert F. Berg (not shown) of the National Institutes of Standards and Technology, Gaithersburg, MD.

  3. Critical Viscosity of Xenon team

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The Critical Viscosity of Xenon Experiment (CVX-2) on the STS-107 Research 1 mission in 2002 will measure the viscous behavior of xenon, a heavy inert gas used in flash lamps and ion rocket engines, at its critical point. The thermostat for CVX sits inside the white cylinder on a support structure (at left) that is placed inside a pressure canister. A similar canister (right) holds the electronics and control systems. The CVX-2 arrangement is identical. The principal investigator is Dr. Robert F. Berg (left) of the National Institutes of Standards and Technology, Gaithersburg, MD.

  4. Critical dimension: MEMS road map

    NASA Astrophysics Data System (ADS)

    Poulingue, Marc; Knutrud, Paul

    2007-03-01

    The use of Micro-Electro-Mechanical Systems (MEMS) technology in mechanical, biotechnology, optical, communications, and ink jet is growing. Critical dimensions in MEMS devices are getting smaller and processes are constantly facing new metrology challenges. This paper will examine some critical dimension metrology needs and challenges for MEMS using resist-on-silicon structures. It is shown that the use of automated optical CD metrology can meet emerging measurement requirements while bringing the advantages of a non-destructive, high throughput and precise methodology.

  5. Critical phenomena of invariant circles

    SciTech Connect

    Hu, B.; Shi, J. ); Kim, S. )

    1991-04-15

    Some novel critical phenomena are discovered in a class of nonanalytic twist maps. It is found that the degree of inflection {ital z} plays a role reminiscent of that of dimensionality in phase transitions with {ital z}=2 and 3 corresponding to the lower and upper critical dimensions, respectively. Moreover, recurrence of invariant circles has also been observed. An inverse residue criterion,'' complementary to the residue criterion'' for the determination of the disappearance point, is introduced to determine the reappearance point of invariant circles.

  6. Criticality and unpredictability in macroevolution

    NASA Astrophysics Data System (ADS)

    Soléand, Ricard V.; Manrubia, Susanna C.

    1997-04-01

    A recently presented model of large-scale evolution exhibiting self-organized criticality is explored from the dynamical point of view. It is shown that the system approaches the critical state in an anomalous way, with a dynamical exponent z=0. At the same time, the complexity of the interactions among species increases, leading to higher unpredictability. The dynamic evolution is able to generate phylogenetic fractal trees with dimension close to the one obtained from real taxonomy. Some analytic results are presented and an interesting interpretation of the macroevolutionary process is suggested.

  7. Criticality measurements for SNM accountability

    SciTech Connect

    Bohman, J.; Martin, E.R.; Butterfield, K.; Paternoster, R.

    1998-03-01

    Based on extensive operating experience with the Godiva IV fast metal burst assembly at Los Alamos National Laboratory, the authors were able to create data plots for reactivity worths of standard configurations at various temperatures and room return locations. These plots show that the material uncertainties in criticality measurements are within {+-} 20 grams out of the 65.4 kilogram HEU Godiva core. This is superior to active neutron well coincidence counter (AWCC) measurements. The criticality measurements have the additional advantage of not requiring disassembly of the reactor. No disassembly means the measurement takes less time--it can be done during each operation--and there is less dose to measurement personnel.

  8. Davies Critical Point and Tunneling

    NASA Astrophysics Data System (ADS)

    La, Hoseong

    2012-04-01

    From the point of view of tunneling, the physical meaning of the Davies critical point of a second-order phase transition in the black hole thermodynamics is clarified. At the critical point, the nonthermal contribution vanishes so that the black hole radiation is entirely thermal. It separates two phases: one with radiation enhanced by the nonthermal contribution, the other suppressed by the nonthermal contribution. We show this in both charged and rotating black holes. The phase transition is also analyzed in the cases in which emissions of charges and angular momenta are incorporated.

  9. Critical Point in Complex Plasmas

    SciTech Connect

    Khrapak, S.A.; Morfill, G.E.; Ivlev, A.V.; Thomas, H.M.; Beysens, D.A.; Zappoli, B.; Fortov, V.E.; Lipaev, A.M.; Molotkov, V.I.

    2006-01-13

    The occurrence of liquid-vapor phase transition and the possible existence of a critical point in complex plasmas--systems that consist of charged micrograins in a neutralizing plasma background--is investigated theoretically. An analysis based on the consideration of the intergrain interaction potential suggests that under certain conditions systems near and at the critical point should be observable. Measurements under microgravity conditions would appear to be required. The analysis aims at determining the plasma parameter regime most suitable for planned experimental investigations.

  10. What Is a Pediatric Critical Care Specialist?

    MedlinePlus

    ... Email Print Share What is a Pediatric Critical Care Specialist? Page Content Article Body If your child ... PICU. What Kind of Training Do Pediatric Critical Care Specialists Have? Pediatric critical care specialists are medical ...

  11. Critical Thinking or Cony Cozenage.

    ERIC Educational Resources Information Center

    Matulich, Loretta

    Teachers of history, introductory chemistry, and literature from Portland State University, Portland Community College, Clark College, Mt. Hood Community College, and Clackamas Community College (Oregon) have been working together to foster critical thinking in their students. Teachers in these disciplines have been meeting at their respective…

  12. Critical Reflection as Doctoral Education

    ERIC Educational Resources Information Center

    Brookfield, Stephen D.

    2015-01-01

    This chapter considers how doctoral education, particularly in applied settings such as education, social work, counseling, and health care, could be reimagined if it was organized around the idea and process of critical reflection: of helping students to better understand how power operates in educational environments and how students' sense of…

  13. Critical Social Theory: A Portrait

    ERIC Educational Resources Information Center

    Torres, Carlos A.

    2012-01-01

    The term Critical Social Theory is employed in this article following the tradition of the Frankfurt School, and particularly the work of Herbert Marcuse and his interpretation of the political and social philosophy of Hegel and Marx. Discussing the contribution of G.W.F. Hegel to social theory Marcuse argued that: "Hegel's system brings to a…

  14. The critically ill immunosuppressed patient

    SciTech Connect

    Parrillo, J.E.; Masur, H. )

    1987-01-01

    This book discusses the papers on the diagnosis and management of immunosuppressed patient. Some of the topics are: life-threatening organ failure in immunosuppressed patients; diagnosis and therapy of respiratory disease in the immunosuppressed patient; CNS complication of immunosuppression; infections; antineoplastic therapy of immunosuppressed patient; radiation therapy-issues in critically ill patient; AIDS; and management of bone marrow transplant patients.

  15. University Rankings in Critical Perspective

    ERIC Educational Resources Information Center

    Pusser, Brian; Marginson, Simon

    2013-01-01

    This article addresses global postsecondary ranking systems by using critical-theoretical perspectives on power. This research suggests rankings are at once a useful lens for studying power in higher education and an important instrument for the exercise of power in service of dominant norms in global higher education. (Contains 1 table and 1…

  16. Mock Trials and Critical Thinking.

    ERIC Educational Resources Information Center

    Karraker, Meg Wilkes

    1993-01-01

    One college teacher's use of mock trials in sociology instruction is described. Students are assigned roles as petitioner, respondent, attorneys, judge, courtroom staff, witnesses, reporters, and jurors. Pretrial investigations provide experience in information-gathering and critical thinking. Posttrial debriefing reveals others' thinking…

  17. High critical current superconducting tapes

    DOEpatents

    Holesinger, Terry G.; Jia, Quanxi; Foltyn, Stephen R.

    2003-09-23

    Improvements in critical current capacity for superconducting film structures are disclosed and include the use of a superconducting RE-BCO layer including a mixture of rare earth metals, e.g., yttrium and europium, where the ratio of yttrium to europium in the RE-BCO layer ranges from about 3 to 1 to from about 1.5 to 1.

  18. Literary Criticism and the Imagination.

    ERIC Educational Resources Information Center

    Lee, James O.

    To increase a student's insight into imaginative works, help him relate his personal experience to the metaphoric structure of literature, and bring him to perceive the value of an educated imagination, the teacher should introduce him to literary analysis and various approaches to literary form. Although a perfect critical system which…

  19. The Critical Point Facility (CPF)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The Critical Point Facility (CPF) is an ESA multiuser facility designed for microgravity research onboard Spacelab. It has been conceived and built to offer investigators opportunities to conduct research on critical point phenomena in microgravity. This facility provides the high precision and stability temperature standards required in this field of research. It has been primarily designed for the purpose of optical investigations of transparent fluids. During a Spacelab mission, the CPF automatically processes several thermostats sequentially, each thermostat corresponding to an experiment. The CPF is now integrated in Spacelab at Kennedy Space Center, in preparation for the International Microgravity Lab. mission. The CPF was designed to submit transparent fluids to an adequate, user defined thermal scenario, and to monitor their behavior by using thermal and optical means. Because they are strongly affected by gravity, a good understanding of critical phenomena in fluids can only be gained in low gravity conditions. Fluids at the critical point become compressed under their own weight. The role played by gravity in the formation of interfaces between distinct phases is not clearly understood.

  20. Critical Literacy and Social Justice

    ERIC Educational Resources Information Center

    Comber, Barbara

    2015-01-01

    Given the global escalation of gaps between rich and poor, contemporary work in critical literacy needs to overtly question the politics of poverty. How and where is poverty produced, by what means, by whom and for whom and how are educational systems stratified to provide different kinds of education to the rich and the poor? Yet rather than…