Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome

Gothelf, Doron; Presburger, Gadi; Levy, Darya; Nahmani, Ariela; Burg, Merav; Berant, Michael; Blieden, Leonard C.; Finkelstein, Yehuda; Frisch, Amos; Apter, Alan; Weizman, Abraham

doi:10.1002/ajmg.b.20144

Cited by 79 publications

(58 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Attention-deficit/ hyperactivity disorder (ADHD) is one of the most common psychiatric problems associated with 22q11DS in children. ADHD, primarily the inattentive subtype, is present in 35-55% of 22q11DS cases (Gothelf et al 2004a). In addition, approximately 11% of children with 22q11DS are autistic, and these children show greater developmental delay than those without autistic spectrum disorder (Fine et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia

Arinami

2006

J Hum Genet

View full text Add to dashboard Cite

Schizophrenia is a severe, debilitating mental disorder characterized by profound disturbances of cognition, emotion and social functioning. The lifetime morbid risk is surprisingly uniform at slightly less than 1% across different populations and different cultures. The evidence of genetic risk factors is our strongest clue to the cause of schizophrenia. Linkage and association analyses have identified genes associated with the development of schizophrenia. However, most of the alleles or haplotypes identified thus far have only a weak association or are reported to be population specific. A deletion of 22q11.2 that causes the most common microdeletion syndrome (22q11DS) with an estimated prevalence of 1:2,500-1:4,000 live births may represent one of the greatest known genetic risk factors for schizophrenia. Schizophrenia is a late manifestation in approximately 30% of patients with 22q11.2 deletion, comparable to the risk to offspring of two parents with schizophrenia. Clinical and neuroimaging assessments indicate that 22q11DS-schizophrenia is a neurodevelopmental model of schizophrenia. Recent studies have provided evidence that haploinsufficiency of TBX1 is likely to be responsible for many of the physical features associated with the deletion. Most of the genes in the 22q11 deletion region are conserved together on mouse chromosome 16, enabling the generation of mouse models. Similarities in the cardiovascular and other phenotypes between 22q11DS patients and mouse models can provide important insights into roles of genes in neurobehavioral phenotypes. Because more than one gene in the 22q11DS region is likely to contribute to the marked risk for schizophrenia, further extensive studies are necessary. Analyses of 22q11DS will help clarify the molecular pathogenesis of schizophrenia.

show abstract

Section: Introductionmentioning

confidence: 99%

Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia

Arinami

2006

J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric morbidity in children with VCFS, affecting approximately one-third to two-fifths of children (Antshel et al, 2006;Gothelf et al, 2004a). In addition to ADHD, mood, anxiety and oppositional defiant disorders are observed at increased prevalence rates compared to the general population (Antshel et al, 2006;Feinstein et al, 2002;Gothelf et al, 2004b;Papolos et al, 1996;Vogels et al, 2002).…”

mentioning

confidence: 99%

Associations Between Performance on the Rey-Osterrieth Complex Figure and Regional Brain Volumes in Children with and without Velocardiofacial Syndrome

Antshel¹,

Peebles²,

AbdulSabur³

et al. 2008

Developmental Neuropsychology

View full text Add to dashboard Cite

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race and gender-ratio comparable sample of 59 control participants were included in the project. Participants received a MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white matter. Brain -behavior relationships include: (a) for both groups, parietal volumes (both gray and white matter) predicted ROCF Copy Organization performance and frontal volumes (both gray and white matter) predicted ROCF Copy Accuracy performance; (b) for controls, frontal white matter also predicted ROCF Copy Organization performance; (c) ROCF Recall Organization performance was best predicted by frontal gray matter volume only in our controls; ROCF Recall Accuracy performance was best predicted by frontal gray matter volume in both groups; and (d) in children with VCFS, performance on the ROCF-Copy Structural Elements Accuracy scale was predicted by right hemisphere white matter volume. Our hypotheses were also retested using IQmatched and whole brain volume-matched subsamples. Identical results were obtained in these analyses. Assumptions about the organization of and the localization of the brain structures that subserve specific cognitive functions in the typically developing brain may not apply in the abnormally developing brain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptVelocardiofacial syndrome (VCFS), a chromosomal deletion disorder of 22q11.2 (3 Mb, 25-30 genes) affects 1 in 2000-5000 individuals . The deletion syndrome is associated with multiple congenital anomalies, including cardiac malformations, hearing loss, hypocalcaemia, velopharyngeal insufficiency and cleft palate (Ryan et al., 1997). Phenotypic facial abnormalities include a long face, pear-shaped nose, small ears with overfolded helicies, and vertically narrow eyes (Antshel et al., 2005). VCFS is associated with cognitive and developmental delays and the vast majority of children with VCFS experience academic difficulties, especially in math (Simon et al., 2002;Swillen et al., 1997;Swillen et al., 1999). Executive functioning deficits including difficulties shifting attention and a poorly developed working memory have also been indicated (Woodin et al., 2000). Most, but not all, children with VCFS exhibit deficits in abstract and nonverbal reasoning and visuospatial abilities (Moss et al., 1999). Some have hypothesized that VCFS is an exemplar of the nonverbal learning disability (NLD; Rourke et al., 2002;Swillen et al., 1999).The VCFS behavioral phenotype includes poor social skills, introversion, disinhibition, impulsivity, anxiet...

show abstract

“…There is also evidence that variation in the gene encoding vascular endothelial growth factor may modify the cardiovascular phenotype in humans who are hemizgyous for the 22q11.2 deletion (Stalmans et al, 2003). Moreover, it has been shown that attention deficit hyperactivity disorder (ADHD) in patients with 22q11.2 deletion syndrome is associated with both patient gender and family history of ADHD (Gothelf et al, 2004).Individuals with the 22q11.2 deletion syndrome present with a range of structural malformations of the palate, including cleft lip, overt cleft palate, submucous cleft palate, and bifid uvula (McDonald-McGinn et al, 1997;Ryan et al, 1997). In addition, patients may present with velopharyngeal inadequacy, with or without an associated structural malformation of the palate (McDonald-McGinn et al, 1997;Ryan et al, 1997).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Evaluation of Potential Modifiers of the Palatal Phenotype in the 22q11.2 Deletion Syndrome

Driscoll

Boland

Emanuel

et al. 2006

Cleft Palate-Craniofac J

View full text Add to dashboard Cite

Objective-To evaluate potential modifiers of the palatal phenotype in individuals with the 22q11.2 deletion syndrome.Design-Data from 356 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the palatal phenotype. Specifically, subjects with and without velopharyngeal inadequacy and/or structural malformations of the palate were compared with respect to gender, race, and genotype for variants of seven genes that may influence palatal development.Methods-The chi-square test or Fisher exact test was used to evaluate the association between palatal phenotype and each potential modifier. Odds ratios and their associated 95% confidence intervals were used to measure the magnitude of the association between palatal phenotype, subject gender and race, and each of the bi-allelic variants.Results-The palatal phenotype observed in individuals with the 22q11.2 deletion syndrome was significantly associated with both gender and race. In addition, there was tentative evidence that the palatal phenotype may be influenced by variation within the gene that encodes methionine synthase.Conclusions-Variation in the palatal phenotype observed between individuals with the 22q11.2 deletion syndrome may be related to personal characteristics such as gender and race as well as variation within genes that reside outside of the 22q11.2 region. Keywords chromosome 22q11.2 deletion; genes; genotype; palate; penetrance; phenotype Hemizygous deletion of the chromosome 22q11.2 region results in a syndromic phenotype that encompasses the DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Population-based estimates of the prevalence of this deletion range from 1 in 4500 to 1 in 7100 births (Botto et al., 2003;Tezenas du Montcel et al., 1996;Oskarsdottir et al., 2004), making it the most frequent known interstitial deletion in humans. The majority of individuals with the 22q11.2 deletion syndrome have a de novo three-megabase deletion. However, approximately 10% of patients with the 22q11.2 deletion syndrome have an inherited deletion, and approximately 10% have a smaller deletion (1.5 Mb) (Saitta et al., 2004;Yamagishi and Srivastava, 2003).The phenotypic consequences of hemizygous deletion of chromosome 22q11.2 are remarkably variable and can include cardiac, thymic, parathyroid, craniofacial, developmental, neurologic, and behavioral manifestations. None of these features appears to be fully penetrant, and each exhibits variable expressivity. For example, approximately 75% of patients with the 22q11.2 deletion syndrome have a cardiac defect, and a range of malformations (e.g., tetralogy of Fallot, interrupted aortic arch, septal defects) is observed among those who have such a defect (McDonald-McGinn et al., 1997;Ryan et al., 1997).The variability in the 22q11.2 deletion syndrome phenotype is largely unexplained. Variability is observed across unrelated patients and between affected family members who have presumably inherited identical deletions (Desmaze et al., 1993;McLe...

show abstract

Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome

Cited by 79 publications

References 30 publications

Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia

Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia

Associations Between Performance on the Rey-Osterrieth Complex Figure and Regional Brain Volumes in Children with and without Velocardiofacial Syndrome

Evaluation of Potential Modifiers of the Palatal Phenotype in the 22q11.2 Deletion Syndrome

Contact Info

Product

Resources

About