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Deletion Syndrome (deletion + syndrome)
Selected AbstractsLoss of the Potassium Channel ,-Subunit Gene, KCNAB2, Is Associated with Epilepsy in Patients with 1p36 Deletion SyndromeEPILEPSIA, Issue 9 2001Heidi A. Heilstedt Summary: ,Purpose: Clinical features associated with chromosome 1p36 deletion include characteristic craniofacial abnormalities, mental retardation, and epilepsy. The presence and severity of specific phenotypic features are likely to be correlated with loss of a distinct complement of genes in each patient. We hypothesize that hemizygous deletion of one, or a few, critical gene(s) controlling neuronal excitability is associated with the epilepsy phenotype. Because ion channels are important determinants of seizure susceptibility and the voltage-gated K+ channel ,-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype. Methods: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2. Clinical details were obtained by neurologic examination and EEG. Results: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG. The majority of patients have a severe seizure phenotype, including infantile spasms. In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms. Conclusions: Lack of the , subunit would be predicted to reduce K+ channel,mediated membrane repolarization and increase neuronal excitability, suggesting a possible relation between loss of this gene and the development of seizures. Because some patients with seizures were not deleted for KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy. [source] Further delineation of 9q22 deletion syndrome associated with basal cell nevus (Gorlin) syndrome: Report of two cases and review of the literatureCONGENITAL ANOMALIES, Issue 1 2009Kayono Yamamoto ABSTRACT Basal cell nevus syndrome (BCNS; Gorlin syndrome) is an autosomal dominant disorder, characterized by a predisposition to neoplasms and developmental abnormalities. BCNS is caused by mutations in the human homolog of the Drosophila patched gene-1, PTCH1, which is mapped on chromosome 9q22.3. Nonsense, frameshift, in-frame deletions, splice-site, and missense mutations have been found in the syndrome. Haploinsufficiency of PTCH1, which is caused by interstitial deletion of 9q22.3, is also responsible for the syndrome. To date, 19 cases with interstitial deletion of long arm of chromosome 9 involving the region of q22 have been reported. We describe two unrelated patients with some typical features of BCNS associated with deletion of 9q21.33-q31.1 and determined the boundary of the deletion by fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. The results showed that the size of deletions is between 15.33 and 16.04 Mb in patient 1 and between 18.08 and 18.54 Mb in patient 2. Although the size and breakpoints were different from those of previously reported cases, the clinical features are common to patients with 9q22 deletion associated with BCNS. Delineation of the 9q22 deletions and further consideration of the genes responsible for the characteristic manifestations may provide insight into this newly recognized deletion syndrome. [source] Candidate genes and the behavioral phenotype in 22q11.2 deletion syndromeDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2008Sarah E. Prasad Abstract 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 for the development of schizophrenia, with only a greater risk conferred by being the child of two parents with schizophrenia or the monozygotic co-twin of an affected individual. Both linkage and association studies of people with schizophrenia have implicated several susceptibility genes, of which three are in the 22q11.2 region; catechol- o -methyltransferase (COMT), proline dehydrogenase (PRODH), and Gnb1L. In addition, variation in Gnb1L is associated with the presence of psychosis in males with 22q11.2DS. In mouse models of 22q11.2DS, haploinsufficiency of Tbx1 and Gnb1L is associated with reduced prepulse inhibition, a schizophrenia endophenotype. The study of 22q11.2DS provides an attractive model to increase our understanding of the development and pathogenesis of schizophrenia and other psychiatric disorders in 22q11.2DS and in wider population. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:26,34. [source] Our evolving understanding of 22q.11 deletion syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2005Fiona Connell No abstract is available for this article. [source] Haemostatic management of surgery for imperforate anus in a patient with 13q deletion syndrome with combined deficiency of factors VII and XHAEMOPHILIA, Issue 1 2009H. KUROSAWA No abstract is available for this article. [source] Autoimmune cytopenias in the 22q11.2 deletion syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2003J. K. Davies Summary We describe two cases of recurrent autoimmune cytopenias, which were subsequently diagnosed with a 22q11.2 deletion/DiGeorge syndrome. The cases are of particular interest as both possessed limited clinical features of this syndrome, and the investigation of haematological abnormalities led to the establishment of a definitive genetic diagnosis. [source] Core neuropsychological characteristics of children and adolescents with 22q11.2 deletionJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 8 2010C. Jacobson Abstract 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 profile in 22qDS. Methods We examined intelligence, memory, reading and mathematical processes in 31 children/adolescents with 22qDS, selected for educational underachievement and an absence of psychiatric diagnoses, using standardised, psychometrically matched instruments that specify how typical a score is for a given intelligence quotient (IQ). Results Corroborating earlier findings, verbal IQ was significantly superior to performance IQ; verbal memory and basic reading were relative strengths; and visual/spatial memory was a relative weakness. All four findings transcended performance characteristics that are typical of low-IQ individuals. Rote learning yielded the highest score; reading comprehension, numerical operations and mathematical reasoning were among the lowest-performed academic domains. Albeit in the expected direction, performance in the respective components could not be clearly differentiated from what is IQ-appropriate. Conclusions A superiority of verbal intelligence over non-verbal intelligence, relative strengths in verbal memory and basic reading, and a relative weakness in visual/spatial memory are likely to be core characteristics of children/adolescents with 22qDS, transcending performance features that are typical of individuals with low IQ. [source] Eosinophilic intracytoplasmic inclusions in Purkinje neurons of childrenNEUROPATHOLOGY, Issue 1 2009Viktor Zherebitskiy Eosinophilic intracytoplasmic inclusions have been rarely described in Purkinje neurons of children with a variety of neurological conditions. Here we document these inclusions in five children from 3 to 14 years of age. One child had 7q deletion syndrome and a second had profound motor and cognitive delay ("cerebral palsy") of unknown origin, while three others were neurologically normal prior to death. These inclusions stain with the PAS method, are not strongly ubiquitinated, and are located in the lumen of endoplasmic reticulum. Their appearance in a wide range of disorders and in neurologically normal children suggests that they are a nonspecific protein trafficking anomaly, possibly aggravated under degenerative conditions. [source] A contiguous deletion syndrome of X-linked agammaglobulinemia and sensorineural deafnessPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2001Darko Richter Hearing loss in patients with X-linked agammaglobulinemia is often attributed to recurrent infections. However, recent genetic studies suggest a different etiology in some patients. We present three unrelated patients, 6, 9, and 14 years of age, with large deletions of the terminal portion of the Bruton tyrosine kinase (Btk) gene extending 4.2,19 kb beyond the 3, end of the gene. The DNA immediately downstream of the 3, end of Btk contains the deafness-dystonia protein gene (DDP). Mutations in this gene have recently been shown to underlie the Mohr,Tranebjaerg syndrome, which is characterized by sensorineural deafness, dystonia, and mental deficiency. Besides the immunodeficiency, our patients exhibited progressive sensorineural deafness. The clue to an associated hearing problem was delayed development of speech in one patient and post-lingual deafness noticed between the age of 3,4 years in the other two. These patients have not yet exhibited significant associated neurologic deficits. [source] Refractory autoimmune hemolytic anemia in a patient with chromosome 22q11.2 deletion syndromePEDIATRICS INTERNATIONAL, Issue 5 2004Osamu Sakamoto No abstract is available for this article. [source] Prenatal diagnosis of a 11q deletion syndrome associated with unilateral hydronephrosis diagnosed by 3D ultrasound examinationPRENATAL DIAGNOSIS, Issue 12 2007Magdalena Sanz-Cortes No abstract is available for this article. [source] Ring chromosome 6 in three fetuses: Case reports, literature review, and implications for prenatal diagnosisAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2002Maik Urban Abstract Prenatal and postnatal findings in three fetuses with a ring chromosome 6 are presented, and the literature of this rare cytogenetic disorder is reviewed. The described fetuses illustrate the broad spectrum of the clinical manifestation of ring chromosome 6. In one fetus, the disorder was diagnosed incidentally by a routine amniocentesis due to advanced maternal age. The other two fetuses were hydrocephalic and had other congenital anomalies. Remarkably, the ring chromosome 6 tends to disappear in cultured amniotic fluid cells; karyotyping revealed complete or nearly complete monosomy 6. In contrast, the ring was preserved in high proportions of fetal leukocytes. Postnatal growth retardation is the only consistent finding of this chromosomal disorder. Maternal age is not significantly above average. An additional review of 20 literature cases revealed a striking tendency to hydrocephalus, either due to deficient brain growth or secondary to an aqueductal stenosis. Children with hydrocephalus and ring chromosme 6 tend to display facial dysmorphism and may have additional malformations, growth failure, eye anomalies, and seizures. In contrast, there are two reports on children with a ring chromosome 6 who had short stature, normal appearance, and a normal or almost-normal psychomotor development. In such patients at the mild end of the clinical spectrum, the phenotype is basically restricted to what Kosztolányi. [1987: Hum Genet 75:174,179] delineated as "ring syndrome," comprising "severe growth failure without major malformations, without a specific deletion syndrome, with only a few or no minor anomalies, and mild to moderate mental retardation." This "ring syndrome" is considered to occur independently of the autosome involved in the ring formation. The overall impression from our cases and from the literature review of cases with ring chromosome 6 is that the karyotype-genotype correlation is poor. This makes prognostic counseling of parents difficult and unsatisfactory. Serial targeted ultrasound examinations, especially of the brain, are decisive factors in elucidating the prognosis. © 2002 Wiley-Liss, Inc. [source] Patterns of dysmorphic features in schizophrenia,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001L.E. Scutt Abstract Congenital dysmorphic features are prevalent in schizophrenia and may reflect underlying neurodevelopmental abnormalities. A cluster analysis approach delineating patterns of dysmorphic features has been used in genetics to classify individuals into more etiologically homogeneous subgroups. In the present study, this approach was applied to schizophrenia, using a sample with a suspected genetic syndrome as a testable model. Subjects (n,=,159) with schizophrenia or schizoaffective disorder were ascertained from chronic patient populations (random, n,=,123) or referred with possible 22q11 deletion syndrome (referred, n,=,36). All subjects were evaluated for presence or absence of 70 reliably assessed dysmorphic features, which were used in a three-step cluster analysis. The analysis produced four major clusters with different patterns of dysmorphic features. Significant between,cluster differences were found for rates of 37 dysmorphic features (P,<,0.05), median number of dysmorphic features (P,=,0.0001), and validating features not used in the cluster analysis: mild mental retardation (P,=,0.001) and congenital heart defects (P,=,0.002). Two clusters (1 and 4) appeared to represent more developmental subgroups of schizophrenia with elevated rates of dysmorphic features and validating features. Cluster 1 (n,=,27) comprised mostly referred subjects. Cluster 4 (n,=,18) had a different pattern of dysmorphic features; one subject had a mosaic Turner syndrome variant. Two other clusters had lower rates and patterns of features consistent with those found in previous studies of schizophrenia. Delineating patterns of dysmorphic features may help identify subgroups that could represent neurodevelopmental forms of schizophrenia with more homogeneous origins. © 2001 Wiley-Liss, Inc. [source] 22q11.2 deletion syndrome: behaviour problems of children and adolescents and parental stressCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 6 2008W. Briegel Abstract Background 22q11.2 deletion syndrome can be associated with a variety of somatic symptoms, developmental delays and psychiatric disorders. At present, there is little information on behaviour problems, parental stress and possible relations between these factors. Therefore, this study investigates behaviour problems of children and adolescents with 22q11.2DS, and their primary caregivers' stress. Methods Parents of 4,17 year old subjects known to the German 22q11.2 deletion syndrome foundation were anonymously asked to fill out several questionnaires, e.g. the Child Behavior Checklist 4,18 (CBCL/4,18). Results The primary caregivers of 77/126 children [43 males, 34 females, mean age: 8;0 (4;0,16;11) years] sent back filled-out questionnaires. Forty-six of 76 subjects were rated as clinical on at least one of the CBCL-scales. Males had significantly higher scores on the total problems scale and the internalizing problems scale than females. The patients' age correlated with several CBCL-scales. Eleven of 49 subjects were suspicious of an autism spectrum disorder. Compared with the general population, but not with other parents of mentally and/or physically handicapped children, the primary caregivers experienced higher levels of stress, but showed normal life satisfaction. Conclusions In spite of high rates of clinical behaviour problems among children and adolescents with 22q11.2DS and despite increased parental stress, most primary caregivers seem to have effective coping strategies, e.g. partnership support, to sustain normal levels of life satisfaction. [source] Testing and improving experimental parameters for the use of low molecular weight targets in array-CGH experiments,HUMAN MUTATION, Issue 11 2006Marianne Stef Abstract Array,comparative genomic hybridization (CGH) has evolved as a useful technique for the detection and characterization of deletions, and, to a lesser extent, of duplications. The resolution of the technique is dictated by the genomic distance between targets spotted on the microarray, and by the targets' sizes. The use of region-specific, high-resolution microarrays is a specific goal when studying regions that are prone to rearrangements, such as those involved in deletion syndromes. The aim of the present study was to evaluate the best experimental conditions to be used for array-CGH analysis using low molecular weight (LMW) targets. The parameters tested were: the target concentration, the way LMW targets are prepared (either as linearized plasmids or as purified PCR products), and the way the targets are attached to the array-CGH slide (in a random fashion on amino-silane coated slides, or by one amino-modified end on epoxysilane-coated slides). As a test case, we constructed a microarray harboring LMW targets located in the CREBBP gene, mutations of which cause the Rubinstein-Taybi syndrome (RTS). From 10 to 15% of RTS patients have a CREBBP deletion. We showed that aminosilane- and epoxysilane-coated slides were equally efficient with targets above 1,000,bp in size. On the other hand, with the smallest targets, especially those below 500,bp, epoxysilane-coated slides were superior to aminosilane-coated slides, which did not allow deletion detection. Use of the high resolution array allowed us to map intragenic breakpoints with precision and to identify a very small deletion and a duplication that were not detected by the currently available techniques for finding CREBBP deletions. Hum Mutat 27(11), 1143,1150, 2006. © 2006 Wiley-Liss, Inc. [source] Autoimmune cytopenias in the 22q11.2 deletion syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2003J. K. Davies Summary We describe two cases of recurrent autoimmune cytopenias, which were subsequently diagnosed with a 22q11.2 deletion/DiGeorge syndrome. The cases are of particular interest as both possessed limited clinical features of this syndrome, and the investigation of haematological abnormalities led to the establishment of a definitive genetic diagnosis. [source] | ||||||||||||||||