22q11.2 Deletion Syndrome: Attitudes towards Disclosing the Risk of Psychiatric Illness

22q11.2 Deletion Syndrome (22q11.2DS) is a common microdeletion syndrome with multisystem features. There is a strong association with psychiatric disorders. One in every four to five patients develop schizophrenia. Despite studies showing that early diagnosis and treatment are likely to lead to improved outcome, genetic counselors may be reluctant to discuss the risk of psychiatric illness. The aim of this research was to explore parental attitudes and genetic counselors’ perspectives and practice regarding disclosure of the clinical manifestations of 22q11.2DS, particularly the risk of psychiatric illness. We delivered a questionnaire to genetic counselors via established list-serves, 54 of which were completed. We also conducted interviews with four parents of adults with 22q11.2DS and schizophrenia. The majority of counselors and parents felt that the increased risk to develop a psychiatric illness is important to disclose. However, in the initial counseling session when the diagnosis was made in infancy genetic counselors were significantly less likely to discuss the risk of psychiatric disorders compared to other later onset features such as hypothyroidism (41?% vs. 83?%, p?=?0.001). When the diagnosis of 22q11.2DS was made in infancy, counselors’ responses in regard to timing of disclosure about psychiatric illnesses were fairly evenly divided between infancy, childhood and adolescence. In contrast, for other major features of 22q11.2DS, disclosure would predominantly be in infancy. The respondents reported that the discussion of psychiatric issues with parents was challenging due to the stigma associated with mental illness. Some also noted limited knowledge about psychiatric illness and treatment. These results suggest that genetic counselors could benefit from further education regarding psychiatric illness in 22q11.2DS and best strategies for discussing this important subject with parents and patients.     

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

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.     

Atypical Neuropsychological Profile in a Boy with 22q11.2 Deletion Syndrome Keywords:

In this article the general and specific cognitive impairments of the boy R.H. with a de novo deletion 22q11.2 are described. His full-scale IQ was 73, and he obtained only slightly better verbal than non-verbal subtest scores. Neuropsychological assessment revealed specific impairments in perceptual categorization of objects presented suboptimal, matching of unfamiliar faces, and verbal learning and memory. In contrast, he performed in accordance with his intelligence level on other visual perceptual tasks, on non-verbal learning and memory tasks, and on attention tasks. Voxel-wise statistical comparison of a high-resolution T1-weighted magnetic resonance image of R.H’s brain with similar images obtained from 14 normal control children revealed as major abnormalities a reduction of the right inferior parietal and superior occipital lobe, and a bilateral reduction of deep white matter behind the inferior frontal gyrus. These cognitive impairments and MRI abnormalities are not commonly described in 22q11.2 Deletion Syndrome and may indicate a larger heterogeneity in the neurocognitive phenotype than currently evidenced. At least in this boy the microdeletion seems to have interfered with the development and functioning of particular neural subsystems, while the structure and functioning of other subsystems was left intact.     

Assessment of Parental Disclosure of a 22q11.2 Deletion Syndrome Diagnosis and Implications for Clinicians

Most children with chromosome 22q11.2 deletion syndrome (22q11DS) have an IQ in the range that may allow them to be capable of understanding a genetic diagnosis despite mild intellectual disabilities. However, there are no publications that relate to the disclosure of a 22q11DS diagnosis to the affected child, or the factors that influence parents’ disclosure to the child. A pilot study was conducted including eight semi-structured interviews with caregivers of children with 22q11DS, 10 to 17?years of age, to investigate the factors that influence how parents inform their children of the diagnosis. Six of eight participants had disclosed the diagnosis to the child, and most of these parents felt they could have benefited from additional advice from professionals to increase their confidence and success, as well as the child’s comprehension of the information. Those who had not informed the child were uncertain about the words to use, how to initiate the conversation, or were concerned about the child’s level of understanding. Our results demonstrate that genetics professionals should help prepare caregivers for conversations with their children about the diagnosis of 22q11DS, monitor the understanding of the diagnosis over time, and provide ongoing support.     

Socioeconomic Status and Psychological Function in Children with Chromosome 22q11.2 Deletion Syndrome: Implications for Genetic Counseling

The purpose of this study is to examine the association between parental socio-economic status (SES) and childhood neurocognition and behavior in children with chromosome 22q11.2 deletion syndrome (22q11DS). Although undoubtedly, the deletion of genes in the 22q11.2 interval is primarily responsible for the psychological manifestations, little is known about the role of the environment in either mitigating or contributing to these problems. We examined the association of parental socio-economic status (SES) with cognition and behavior in children with 22q11DS (n = 65) and matched healthy control subjects (n = 52), since SES is a component of family resources. We found that in children with 22q11DS, higher SES correlated with better overall functioning (p < .01) and social skills (p < .01), and less frequent oppositional defiant behavior (p < .001). These findings were in contrast to the control subjects in whom SES correlated with cognition and achievement, but not behavior. Our results indicate that environmental factors influence the behavioral phenotype in children with 22q11DS, providing a framework for developing appropriate interventions. As such, genetic counseling for families with 22q11DS may include consideration of family resources and inclusion of other health professionals, such as social workers, to explore with the family available social supports and resources.     

Neuropsychological profile and neuroimaging in patients with 22Q11.2 Deletion Syndrome: a review.

22q11.2 Deletion Syndrome is associated with cognitive, behavioural, and psychiatric problems and is known to affect brain structure. Recently, 22q11.2 Deletion Syndrome has been proposed as a disease model for a genetic subtype of schizophrenia. In this paper we discuss the currently available literature on neurocognitive functioning and brain anatomy in patients with 22q11.2 Deletion Syndrome, and how this contributes to our understanding of the neurobiology of schizophrenia. Research on cognitive functioning in 22q11.2 Deletion Syndrome patients suggests a specific cognitive profile with impairments on arithmetical, visuo-spatial, and executive tasks and relatively preserved language skills. Prominent findings of neuroimaging studies in 22q11.2 Deletion Syndrome patients are: reduction of overall brain volume, midline defects, structural alterations of cerebellum and frontal lobe, white matter abnormalities, and decreased grey matter volumes in parietal and temporal areas. We describe how brain abnormalities in patients with 22q11.2 Deletion Syndrome may contribute to the understanding of the clinical syndrome including cognitive impairments, psychotic symptoms, and social and communication problems.     

22q11.2 deletion syndrome: genetics, neuroanatomy and cognitive/behavioral features keywords.

This paper presents a conceptual review of the genetic underpinnings of 22q11.2 Deletion Syndrome. The neuroanatomical, neuropsychological, behavioral, and psychiatric phenotype associated with 22q11.2 Deletion Syndrome is also explored, including variables that are thought to affect symptom expression. The history of the deletion syndrome is described, and future directions for continued research are discussed.     

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.     

Patient and Family Experiences and Opinions on Adding 22q11 Deletion Syndrome to the Newborn Screen

22q11 deletion syndrome (22qDS) has recently been proposed for addition to the newborn screening panel in Wisconsin and it seems likely that it may soon be considered in other states as well. Input from patients with 22qDS and their family was gathered from 21 phone interviews. Cardiac, palate, hypocalcemia, and multiple anomalies were common reasons for involved patients to be diagnosed, though age at diagnosis ranged from birth to adulthood. Many commented on their struggles with 22qDS, including worries about the future and the patient’s independence. In general, respondents favored newborn screening for 22qDS because it would help prevent some medical problems, increase access to services, explain existing problems, and identify mild cases. However, a minority expressed reservations, including concerns that it would disrupt bonding, could be too costly, and would not be useful for mild cases.     

Domain specific attentional impairments in children with chromosome 22q11.2 deletion syndrome

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 children with the disorder was compared in these tasks with a group of age-matched typically developing children. The children with DS22q11.2 demonstrated impaired spatially based orienting which is consistent with previous findings in this group. Strikingly, the children with DS22q11.2 also demonstrated an improved ability to use object-based cues, relative to the typically developing group. Finally, the children with DS22q11.2 demonstrated an intact inhibition of return system, however, it appears to be delayed developmentally.     

Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome

Dopamine plays a critical role in regulating neural activity in prefrontal cortex (PFC) and modulates cognition via a hypothesized inverse U function. We investigated PFC function in children with chromosome 22q11.2 deletion syndrome (22q11.2DS) in which one copy of catechol-O-methyltransferase (COMT) is deleted, thereby shifting them toward the lower end of dopamine turnover on the nonlinear function. A common polymorphism with valine to methionine substitution alters COMT activity that results in higher enzyme activity in the valine variant. Twenty-seven children with 22q11.2DS between 7 and 14 years old, and 21 age-matched typically developing children, performed a modified version of the Attention Network Test. Children with a single valine allele showed a reduction in response times when trials with incongruent flankers were repeated, whereas those who were hemizygous for the methionine allele did not show the same context-based response facilitation. Our results support that a single gene, COMT, could modulate PFC-dependent cognition.     

Effects of selective forebrain noradrenaline loss on behavioral inhibition in the rat.

Virtually total depletion of cortical and hippocampal noradrenaline by stereotaxic injection of 6-hydroxydopamine into the fibers of the dorsal noradrenergic bundle produced no impairment in acquisition learning of a runway response for food reward. Extinction of this response, once learned, was markedly slower in the treated group than in controls, the treated animals perseverating in rapid running to the goal box even with no food present there. Similarly, no impairment was found on acquisition of a continuously reinforced lever-pressing response for food. Extinction of this response, however, was again slower in the treated group. Subsequent acquisition of a successive light-dark discrimination task was also slower in the treated group, with these animals perseverating in responding to the negative stimulus. Although selective forebrain noradrenaline loss does not impair the acquisition of appetitive responses, the suppression of responses in the absence of reward is impeded. A parallel is drawn with those effects found classically after surgical lesion to the hippocampus.     

Effects of fixed and variable ratios on human behavioral variability.

The effect that ratio schedules of reinforcement had upon variability of responding was investigated in college students. Subjects were paid $0.02 contingent upon completion of eight presses, distributed in any combination across two push buttons; 256 different sequences were possible. Sequence emission was reinforced according to fixed- and variable-ratio schedules. Ratio requirements of 1, 2, 4 and 8 were presented in alternate components of a multiple schedule. The variability engendered by variable-ratio schedules was also compared to that engendered by fixed ratios. Variability increased with ratio size, irrespective of whether the schedule requirement was fixed or variable. The data demonstrate the similarity between the determinants of human and nonhuman variability, and they illustrate the role of ratio size in determining variability in operant behavior.     

Relations among children's perceptions of maternal behavior,attributional styles,and behavioral symptomatology in maltreated children

This investigation examined relations among perceptions of mothers, attributional style, and counselor-rated behavior problems in 187 school age children (88 maltreated, 99 nonmaltreated). Hypotheses regarding the presence of higher levels of internalizing and externalizing behavior problems in maltreated children were confirmed. Attributional style was found to function as a moderator of externalizing behavior problems, suggesting that attributional style exerts a protective role against the harmful effect of child maltreatment. Perceptions of mothers were found to operate as a mediator of both internalizing and externalizing symptomatology, with maltreated children with less positive perceptions of their mothers exhibiting greater internalizing and externalizing behavior problems. These findings advance knowledge of how cognitive processes contribute to behavior problems in maltreated children and possess implications for prevention and intervention efforts.