The 22q11.2 Deletion in Children

Department of Psychiatry, Utrecht University, Utrecht, Utrecht, Netherlands
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 7.26). 10/2006; 45(9):1104-13. DOI: 10.1097/01.chi.0000228131.56956.c1
Source: PubMed


To examine psychopathology and influence of intelligence level on psychiatric symptoms in children with the 22q11.2 deletion syndrome (22q11DS).
Sixty patients, ages 9 through 18 years, were evaluated. Assessments followed standard protocols, including structured and semistructured interviews of parents, videotaped psychiatric interview, and intelligence assessment of the child. Intelligence level, psychiatric symptoms, and classification provided the main outcome.
High rates of autism spectrum disorders (30 of 60, 50.0%) and psychotic symptoms (16 of 60, 26.7%) were found in this sample. In 7 of 60 (11.7%), the psychotic symptoms interfered with behavior and caused considerable distress. In these cases, the diagnosis of a psychotic disorder was applied. The average age of the children with psychotic symptoms at time of assessment was 14.2 years. Although it is likely that the high rate of psychopathology in this sample is to some extent associated with the lower level of cognitive function, a major effect of the degree of cognitive impairment on psychiatric morbidity was not found.
Autism spectrum disorders and subthreshold autistic symptomatology are common in children with 22q11DS. Furthermore, a high rate of psychosis and psychotic symptoms is found in this childhood sample, suggesting an early onset of psychosis in 22q11DS patients. Autistic and psychotic disorders should be considered to be main elements of the behavioral phenotype of 22q11DS children.

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Available from: Petra W J Klaassen, Dec 29, 2013
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    • "Specifically, children with 22q11DS are described as showing more withdrawn behavior, social interaction problems with peers, attention problems, and anxiety problems. This is consistent with several clinical studies in 22q11DS in which high rates of attention deficit disorder with hyperactivity (ADHD) [Niklasson et al., 2001; Gothelf et al., 2005], autism spectrum disorders [Niklasson et al., 2001, 2009; Fine et al., 2005; Antshel et al., 2006; Vorstman et al., 2006] and anxiety and affective disorders [Antshel et al., 2006; Jolin et al., 2009] are reported. There has been some controversy regarding the diagnosis of ASD in 22q11 DS; recent studies have shown that individuals with 22q11 DS and ASD had significant problems in social interaction and communication while stereotyped behaviors were not reported , suggesting a unique type of ASD [Kates et al., 2007; Bruining et al., 2010]. "
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    ABSTRACT: 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. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part C Seminars in Medical Genetics 05/2015; 169(2). DOI:10.1002/ajmg.c.31435 · 3.91 Impact Factor
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    • "High prevalence of psychiatric disorders has been associated with the syndrome. Anxiety disorder, major depressive disorder, attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder may emerge in childhood [Swillen et al., 1999; Gothelf et al., 2004; Niklasson et al., 2005; Antshel et al., 2006; Green et al., 2009; Jolin et al., 2009, 2012; Fabbro et al., 2012; Tang et al., 2013] and schizophrenia spectrum features may emerge in adolescence and early adulthood [Murphy et al., 1999; Bassett et al., 2003; Gothelf et al., 2007; Vorstman et al., 2006; Green et al., 2009; Stoddard et al., 2010; Hooper et al., 2013; Tang et al., 2013]. Multiple congenital, psychiatric and neurocognitive phenotypes observed in 22q11DS enable investigation of interactions among genetic vulnerability and congenital anomalies that may impact intrauterine brain development and be associated with psychiatric disorders. "
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    ABSTRACT: Children with 22q11.2 deletion syndrome (22q11DS) present with congenital heart disease (CHD) and high prevalence of psychiatric disorders and neurocognitive deficits. Although CHD has been implicated in neurodevelopment, its role in the neuropsychiatric outcome in 22q11DS is poorly understood. We investigated whether CHD contributes to the high prevalence of psychiatric disorders and neurocognitive impairments in 22q11DS. Fifty-four children ages 8-14 years with 22q11DS and 16 age-matched non-deleted children with CHD participated. They were assessed using semi-structured interviews and a Computerized Neurocognitive Battery. CHD status was assessed using available medical records. Prevalence of psychiatric disorders and cognitive profiles were compared among the groups. There were no significant differences between the prevalence of psychiatric disorders in the 22q11DS with and without CHD. In 22q11DS with CHD, the prevalence rates were 41% anxiety disorders, 37% ADHD and 71% psychosis spectrum. In 22q11DS without CHD, the rates were 33% anxiety disorders, 41% ADHD and 64% psychosis spectrum. In comparison, the non-deleted CHD group had lower rates of psychopathology (25% anxiety disorders, 6% ADHD, and 13% psychosis spectrum). Similarly, the 22q11DS groups, regardless of CHD status, had significantly greater neurocognitive deficits across multiple domains, compared to the CHD-only group. We conclude that CHD in this sample of children with 22q11.2DS does not have a major impact on the prevalence of psychiatric disorders and is not associated with increased neurocognitive deficits. These findings suggest that the 22q11.2 deletion status itself may confer significant neuropsychiatric vulnerability in this population. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2014; 165(2). DOI:10.1002/ajmg.b.32215 · 3.42 Impact Factor
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    • "The most commonly reported psychiatric disorders are attention deficit/hyperactivity disorder (ADHD),33,34 anxiety20,35,36 autism spectrum disorders,37 mood disorders including major depression and bipolar disorder,38,39 and psychotic disorders.40–42 There has also been substantial research focusing on brain structure and function in 22q11DS.43–45 "
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    ABSTRACT: 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.
    Neuropsychiatric Disease and Treatment 12/2013; 9:1873-1884. DOI:10.2147/NDT.S52188 · 1.74 Impact Factor
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