scholarly journals Speech and language abilities of children with the familial form of 22q11.2 deletion syndrome

Genetika ◽  
2016 ◽  
Vol 48 (1) ◽  
pp. 57-72
Author(s):  
Marijana Rakonjac ◽  
Goran Cuturilo ◽  
Milena Stevanovic ◽  
Ida Jovanovic ◽  
Ljiljana Jelicic-Dobrijevic ◽  
...  
Keyword(s):  
De Novo ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Speech And Language ◽  
Language Abilities ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Congenital Heart Malformations ◽  
Familial Form ◽  
22Q11.2 Microdeletion

The 22q11.2 Deletion Syndrome (22q11.2DS), which encompasses Shprintzen syndrome, DiGeorge and velocardiofacial syndrome, is the most common microdeletion syndrome in humans with an estimated incidence of approximately 1/4000 per live births. After Down syndrome, it is the second most common genetic syndrome associated with congenital heart malformations. The mode of inheritance of the 22q11.2DS is autosomal dominant. In approximately 72 - 94% of the cases the deletion has occurred de novo, while in 6 to 28% of patients deletion was inherited from a parent. As a part of a multidisciplinary study we examined the speech and language abilities of members of two families with inherited form of 22q11.2DS. The presence of 22q11.2 microdeletion was revealed by fluorescence in situ hybridization (FISH) and/or multiplex ligation-dependent probe amplification (MLPA). In one family we detected 1.5 Mb 22q11.2 microdeletion, while in the other family we found 3Mb microdeletion. Patients from both families showed delays in cognitive, socio-emotional, speech and language development. Furthermore, we found considerable variability in the phenotypic characteristics of 22q11.2DS and the degree of speech-language pathology not only between different families with 22q11.2 deletion, but also among members of the same family. In addition, we detected no correlation between the phenotype and the size of 22q11.2 microdeletion.

scholarly journals Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 977
Author(s):  
Małgorzata Karbarz
Keyword(s):  
Clinical Manifestations ◽  
Monozygotic Twins ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Chromosome 22 ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Transcript Levels ◽  
22Q11.2 Microdeletion ◽  
Genome Level

Chromosomal 22q11.2 deletion syndrome (22q11.2DS) (ORPHA: 567) caused by microdeletion in chromosome 22 is the most common chromosomal microdeletion disorder in humans. Despite the same change on the genome level, like in the case of monozygotic twins, phenotypes are expressed differently in 22q11.2 deletion individuals. The rest of the genome, as well as epigenome and environmental factors, are not without influence on the variability of phenotypes. The penetrance seems to be more genotype specific than deleted locus specific. The transcript levels of deleted genes are not usually reduced by 50% as assumed due to haploinsufficiency. 22q11.2DS is often an undiagnosed condition, as each patient may have a different set out of 180 possible clinical manifestations. Diverse dysmorphic traits are present in patients from different ethnicities, which makes diagnosis even more difficult. 22q11.2 deletion syndrome serves as an example of a genetic syndrome that is not easy to manage at all stages: diagnosis, consulting and dealing with.

scholarly journals Clozapine-induced myocarditis in an adolescent male with DiGeorge Syndrome

2018 ◽  
Vol 8 (6) ◽  
pp. 313-316 ◽  
Author(s):  
Ann Marie Ruhe ◽  
Imran Qureshi ◽  
David Procaccini
Keyword(s):  
Digeorge Syndrome ◽  
Rare Complication ◽  
22Q11.2 Deletion Syndrome ◽  
Adolescent Male ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Clozapine Therapy ◽  
Chromosomal Disorder ◽  
Congenital Heart Malformations ◽  
Pediatric Populations

Abstract DiGeorge Syndrome (22q11.2 deletion syndrome) is a chromosomal disorder associated with both congenital heart malformations and schizophrenia, which is often treatment-resistant and may warrant treatment with clozapine. Clozapine-induced myocarditis (CIM) is a rare complication of clozapine therapy, with a reported incidence ranging from 0.015% to 3%. Fulminant CIM has a nonspecific presentation in both adult and pediatric populations and a mortality rate approaching 50%. Few cases of pediatric CIM have been documented in the literature. This report highlights a case of CIM in an adolescent male with DiGeorge Syndrome whose clinical course was characterized by a subtle, nonspecific presentation and resolution with supportive care.

scholarly journals Episodic Behavioural Regression in an 8-Year-Old Female: Sequelae of 22q11.2 Duplication Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
A. Bahji ◽  
S. Khalid-Khan
Keyword(s):  
Case Reports ◽  
22Q11.2 Deletion Syndrome ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Medical Illness ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Potential Risk Factors ◽  
22Q11.2 Duplication Syndrome ◽  
Duplication Syndrome

22q11.2 duplication syndrome is a recently discovered genetic syndrome with unclear neuropsychiatric sequelae. While its connection to 22q11.2 deletion syndrome is actively investigated, case reports on the neuropsychiatric sequelae of affected individuals have been previously described, largely focusing on comorbid autism spectrum disorder. Here, we present the case of an 8-year-old female experiencing episodes of severe behavioural regression following medical illness. We analyze the case and relate it to the available literature and identify potential risk factors.

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study

2018 ◽  
Vol 48 (1) ◽  
pp. 20-26 ◽  
Author(s):  
R. Weinberger ◽  
O. Weisman ◽  
Y. Guri ◽  
T. Harel ◽  
A. Weizman ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
22Q11.2 Deletion Syndrome ◽  
Structured Interview ◽  
Neurocognitive Functioning ◽  
Deletion Syndrome ◽  
Psychotic Symptoms ◽  
Psychiatric Evaluation ◽  
Neurocognitive Performance ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome

AbstractBackgroundThe 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories.MethodsForty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12–35 years, were assessed at two time points (15.2 ± 2.1 months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB).Results22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS.ConclusionsOur results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

scholarly journals 22q11.2 Low Copy Repeats Expanded in the Human Lineage

2021 ◽  
Vol 12 ◽  
Author(s):  
Lisanne Vervoort ◽  
Nicolas Dierckxsens ◽  
Zjef Pereboom ◽  
Oronzo Capozzi ◽  
Mariano Rocchi ◽  
...  
Keyword(s):  
Human Population ◽  
De Novo ◽  
Phenotypic Variability ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Species Variation ◽  
Human Lineage ◽  
22Q11.2 Deletion ◽  
Functional Studies ◽  
Low Copy Repeats

Segmental duplications or low copy repeats (LCRs) constitute duplicated regions interspersed in the human genome, currently neglected in standard analyses due to their extreme complexity. Recent functional studies have indicated the potential of genes within LCRs in synaptogenesis, neuronal migration, and neocortical expansion in the human lineage. One of the regions with the highest proportion of duplicated sequence is the 22q11.2 locus, carrying eight LCRs (LCR22-A until LCR22-H), and rearrangements between them cause the 22q11.2 deletion syndrome. The LCR22-A block was recently reported to be hypervariable in the human population. It remains unknown whether this variability also exists in non-human primates, since research is strongly hampered by the presence of sequence gaps in the human and non-human primate reference genomes. To chart the LCR22 haplotypes and the associated inter- and intra-species variability, we de novo assembled the region in non-human primates by a combination of optical mapping techniques. A minimal and likely ancient haplotype is present in the chimpanzee, bonobo, and rhesus monkey without intra-species variation. In addition, the optical maps identified assembly errors and closed gaps in the orthologous chromosome 22 reference sequences. These findings indicate the LCR22 expansion to be unique to the human population, which might indicate involvement of the region in human evolution and adaptation. Those maps will enable LCR22-specific functional studies and investigate potential associations with the phenotypic variability in the 22q11.2 deletion syndrome.

scholarly journals Incidental finding of APC deletion in a child: double trouble or double chance? – a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Erica Rosina ◽  
Berardo Rinaldi ◽  
Rosamaria Silipigni ◽  
Luca Bergamaschi ◽  
Giovanna Gattuso ◽  
...  
Keyword(s):  
De Novo ◽  
22Q11.2 Deletion Syndrome ◽  
Copy Number Variations ◽  
Velopharyngeal Insufficiency ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
22Q11.2 Deletion ◽  
Poor Growth ◽  
Genome Wide ◽  
A Genome

Abstract Background 22q11.2 deletion syndrome is one of the most common genomic disorders, characterized by the variable presence of facial dysmorphisms, congenital cardiac defects, velopharyngeal insufficiency/cleft palate, thymic hypoplasia/aplasia, immunodeficiency, parathyroid hypoplasia, developmental delay, learning disabilities, psychiatric disorders, renal, ocular, and skeletal malformations, hearing loss and laryngeal abnormalities. Chromosomal microarray (CMA) hybridization is one of the most performed diagnostic tests but as a genome wide analysis, it can point out relevant incidental copy number variations. Case presentation We report the case of a 2-year-old boy that came to our attention for mild psychomotor delay, poor growth, and minor facial anomalies. Considering a diagnosis of 22q11.2 deletion syndrome, we performed CMA that not only confirmed our diagnosis, but also pointed out an additional de novo 5q21.3q22.2 microdeletion, encompassing APC gene. As a result of the genetic testing we enrolled the patient in a tailored surveillance protocol that enabled the early detection of a hepatoblastoma. The child underwent surgical and chemotherapic treatments with complete cancer eradication. Conclusions The concurrent finding of an expected result and an additional deletion of APC gene represents an example of a relevant issue about the health and ethical management of secondary findings revealed by genome-wide tests. Furthermore, this report highlights the need to develop dedicated surveillance guidelines for children with APC-related polyposis and raise the question whether to suspect and screen for APC-related conditions in cases of sporadic hepatoblastomas.

scholarly journals Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

2020 ◽  
Author(s):  
Maria Gudbrandsen ◽  
Anke Bletsch ◽  
Caroline Mann ◽  
Eileen Daly ◽  
Clodagh M Murphy ◽  
...  
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Precentral Gyrus ◽  
22Q11.2 Deletion ◽  
Autism Symptomatology ◽  
Main Effect ◽  
22Q11.2 Microdeletion

Abstract Background: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 Deletion Syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same – or distinct – neural systems that mediate these symptoms in non-deletion carriers. Methods: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n=25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e. idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e. multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. Results: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS ( p <0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. Limitations: We employed a multicenter design to overcome single-site recruitment limitations, however, FreeSurfer derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field-strengths’. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e. 6-25 years). Conclusions: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

scholarly journals Hypocalcemia due to 22q11.2 deletion syndrome diagnosed in adulthood

2018 ◽  
Vol 2018 ◽  
Author(s):  
Maria Cabrer ◽  
Guillermo Serra ◽  
María Soledad Gogorza ◽  
Vicente Pereg
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Neck Surgery ◽  
Hereditary Disease ◽  
Deletion Syndrome ◽  
List Type ◽  
22Q11.2 Deletion ◽  
Genetic Syndrome ◽  
Chromosome 22Q11.2 ◽  
Symptomatic Hypocalcemia ◽  
New Diagnosis

Summary Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic syndrome that may present with hypocalcemia due to primary hypoparathyroidism (PH) at any age. We report a new diagnosis of 22q11.2DS in a 57-year-old man who presented with symptomatic hypocalcemia. It is important to consider genetic causes of hypocalcemia due to PH regardless of age. Learning points: It is important to discard genetic cause of primary hypoparathyroidism in a patient without autoimmune disease or prior neck surgery. A new diagnosis of a hereditary disease has familial implications and needs genetic counselling. It is also important to discard other syndrome’s comorbidities.

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