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22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy.

ABSTRACT: Callous-unemotional (CU) traits are highly disabling behavioral characteristics, common predictors of delinquency and criminality, and pathognomonic for antisocial personality disorder. They are highly heritable, but their specific molecular genetic causes are unknown. Here, we briefly review the literature on neuropsychiatric correlates of 22q11.2 duplication and describe a newly identified case of a 737-kb microduplication within the low copy repeat (LCR) B-D region, involving a 13-yr-old early adoptee with mild developmental delay and severe, chronic antisocial behavior of early childhood onset. When psychiatric symptoms have been reported in relation to duplications in this specific region, 19% of the reports feature aggression-but never previously CU traits-as a component of the phenotype. We discuss the potential implications of gain of function in this chromosomal region for heritable origins of sociopathy and their possible relation to genetic influences on aggression.

SUBMITTER: Vyas S

PROVIDER: S-EPMC6913156 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy.

Vyas Sonam S Constantino John N JN Baldridge Dustin D

Cold Spring Harbor molecular case studies 20191213 6

Callous-unemotional (CU) traits are highly disabling behavioral characteristics, common predictors of delinquency and criminality, and pathognomonic for antisocial personality disorder. They are highly heritable, but their specific molecular genetic causes are unknown. Here, we briefly review the literature on neuropsychiatric correlates of 22q11.2 duplication and describe a newly identified case of a 737-kb microduplication within the low copy repeat (LCR) B-D region, involving a 13-yr-old earl ...[more]

PMID: 31836587

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Project description: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.

Project description:Background22q11.2 deletion syndrome (22q11DS) is a common recurrent neurogenetic condition associated with elevated risk for developmental neuropsychiatric disorders and intellectual disability. Children and adults with 22q11DS often exhibit marked social impairment as well as neurocognitive deficits, and have elevated rates of both autism spectrum disorder (ASD) and psychosis. However, the relationship between the basic processes of social cognition and cognitive ability has not been well studied in 22q11DS. Here, we examined differences in social cognition in 22q11DS, relative to multiple groups of idiopathic neuropsychiatric disorders, and typically developing healthy controls (HC). Additionally, we examined differences in intellectual functioning and its relationship to social cognitive abilities. Finally, we examined the relationship between social cognitive abilities and real-world social behavior.MethodsWe examined social cognition and intellectual functioning in 273 participants (mean age = 17.74 ± 5.18% female = 44.3%): 50 with 22q11DS, 49 youth with first episode psychosis (FEP), 48 at clinical high-risk (CHR) for psychosis, 24 participants with ASD, and 102 HC. Social cognition was assessed using The Awareness of Social Inference Test (TASIT), while reciprocal social behavior was assessed via parent/caregiver ratings on the Social Responsiveness Scale (SRS). Participants were also administered the Wechsler Abbreviated Scale of Intelligence, 2nd edition (WASI-II) to assess intellectual functioning.ResultsThe 22q11DS group exhibited significantly lower social cognitive abilities compared to CHR, FEP, and HC groups after controlling for intellectual functioning, but not in comparison to the ASD group. Significant positive correlations were found between social cognition, as measured by the TASIT and IQ across groups. In contrast, no significant relationships were found between TASIT and real-world social behavior (SRS) for any group.ConclusionsOur findings indicate social cognitive deficits are more prominent in 22q11DS than idiopathic neuropsychiatric conditions across the age range, even after adjusting for global intellectual function. These results contribute to our understanding of the intellectual and social vulnerabilities of 22q11DS in comparison to idiopathic neuropsychiatric disorders. Our findings of robust associations between intellectual ability and social cognition emphasizes the importance of accounting for neurocognitive deficits in social skills interventions and tailoring these existing treatment models for 22q11DS and other populations with intellectual impairment.

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22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy.

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22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy.

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