Impact of Cranial Base Abnormalities on Cerebellar Volume and the Velopharynx in 22q11.2 Deletion Syndrome

2019 ◽  
Vol 57 (4) ◽  
pp. 412-419 ◽  
Author(s):  
Abigail E. Haenssler ◽  
Adriane Baylis ◽  
Jamie L. Perry ◽  
Lakshmi Kollara ◽  
Xiangming Fang ◽  
...  
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Cranial Base ◽  
Deletion Syndrome ◽  
Healthy Children ◽  
22Q11.2 Deletion ◽  
Cerebellar Volume ◽  
Potential Relationship ◽  
Significant Difference ◽  
Cranial Base Angles ◽  
Cerebellum Volume

Objective: The purpose of this study was to analyze the relationship between cranial base, cerebellar, craniofacial, and velopharyngeal (VP) variables in individuals with 22q11.2 deletion syndrome (22q11DS). Methods: Thirteen typically developing healthy children and 13 age- and sex-matched individuals with 22q11DS completed a magnetic resonance imaging scan, which was used to examine craniofacial and VP variables. Results: A statistically significant difference was noted in cerebellum volumes, F 1,24 = 7.947, P = .010, posterior nasal spine to posterior pharyngeal wall (PNS-PPW), F 1,24 = 4.878, P = .037, nasion-sella-basion (NSB) cranial base angles, F 1,24 = 7.253, P = .013, and sella-basion-opisthion (SBO) cranial base angles, F 1,24 = 9.134, P = .006, between children with 22q11DS and controls. The cerebellum volume was significantly reduced and cranial base angles were significantly more obtuse in individuals with 22q11DS. In the 22q11DS group, cerebellum volume was significantly correlated with sella-basion (SB) length, osseous pharyngeal depth, the PNS-PPW length, and velar length ( P < .05). The PNS-PPW length was correlated with SB length, basion-opisthion length, NSB angle, SBO angle, and the VP ratio ( P < .05). Conclusion: This study supports previous findings on anatomical differences among individuals with 22q11DS and has expanded our current understanding of the potential relationship between craniofacial and VP variables in at least a subset of children with 22q11DS. Results provide preliminary insights into the potential relationship between a decrease in cerebellar volume, obtuse cranial base angles, and unfavorable VP dimensions.

scholarly journals Contribution of mitochondrial DNA heteroplasmy to the phenotypic variability in maternally transmitted 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
Boris Rebolledo-Jaramillo ◽  
Maria Gabriela Obregon ◽  
Victoria Huckstadt ◽  
Abel Gomez ◽  
Gabriela M. Repetto
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Congenital Defects ◽  
P Value ◽  
Frequency Change ◽  
22Q11.2 Deletion ◽  
Cardiac Phenotype ◽  
Significant Difference

ABSTRACT22q11.2 deletion syndrome (22q11DS) has an incidence of 1 in 4,000. Most cases occur de novo, but about 10–15% of cases are inherited. Features include congenital heart disease, cleft palate, developmental delay, and other characteristics that can vary even among family members. The presence of nuclear mitochondrial genes in the deleted region, and the requirement of mitochondrial function for proper embryonic development, suggests that intrafamilial variability in maternally transmitted 22q11DS could be explained, at least partially, by variation in mitochondrial DNA (mtDNA). Thus, we sequenced the mtDNA of seventeen 22q11DS mother-child pairs. We identified 29 heteroplasmic variants at the 1% level, and compared the intrafamilial allele frequency change between phenotypically concordant and discordant pairs. We observed a statistically significant difference for the palatal phenotype: p-value = 0.048 (permutation test, 8 concordant vs. 9 discordant pairs), but not for the cardiac phenotype: p-value = 0.568 (6 vs. 11).Mitochondrial function has been primarily studied in mouse models of neurological 22q11DS phenotypes. Our study sets a precedent for considering human mitochondrial variation as a genetic modifier of congenital defects in this syndrome, and although our results are limited by sample size, they suggest a role for mitochondrial variation in the palatal phenotype.

scholarly journals Detecting 22q11.2 Deletion Syndrome Using Flow Cytometry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4207-4207
Author(s):  
Stephen J Markham ◽  
Lisa Bevilaqua ◽  
Haley Zarrin ◽  
Donna McDonald-McGinn ◽  
Elaine Zackai ◽  
...  
Keyword(s):  
Platelet Count ◽  
Conflicts Of Interest ◽  
Flow Cytometric Analysis ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Platelet Disorder ◽  
Significant Difference ◽  
Normal Controls ◽  
Low Expression

Abstract The 22q11.2 deletion syndrome (DS) is a multisystem chromosomal deletion disorder with pleotropic phenotypic presentations that may be subtle. We examine retrospectively whether we can support the diagnosis of 22q11.2DS by flow cytometric analysis of platelets for surface CD42 (GPIb/V/IX) as ~89% of these patients (with the classical deletion) should have a deficiency of GPIbbeta due to loss of one copy of the GPIBB gene. Loss of one copy of GPIBB may result in macrothrombocytopenia and a mild bleeding diathesis. We characterized the bleeding manifestations and the level of expression of the CD42 complex in patients with known 22q11.2 deletion to determine if CD42 levels could be used to assess bleeding risk. We evaluated 56 patients with 22q11.2 deletion and compared them to age-matched controls with normal platelet counts and no bleeding as well as with controls evaluated for concern for platelet disorder (platelet disorder subjects – PDS), mostly other thrombocytopenias. Comparisons were also made for other platelet parameters. Expression of the CD42b (GP1bb) varied in individuals with the 22q11.2 deletion. Although only 30/56 (54%) subjects had low CD42 expression (<70% control), CD42 expression overall in the 22q11.2 deleted patients was significantly lower than in PDS (69±5% vs 93±5% of PDS, p<0.002) or in normal controls (69±5% vs 100±5% of WT, p<0.001). For the total population (22q11.2 DS and PDS subjects), MPV and platelet count were inversely related (R2 0.18, p<0.001), but there was no correlation with either CD41 or CD42 expression. There was no significant difference in MPV or platelet count between PDS and 22q11.2DS subjects. When compared to normal control subjects, MPV was significantly higher in 22q11.2DS subjects compared to normal controls (9.5±0.3 vs 7.8±0.3, p< 0.001) and the platelet count was significantly lower (187±12 vs 295±16, p<0.001). We also examined the expression of CD41 (GPIIb) in subjects with 22q11.2DS as it would be expected that in macrothrombocytes expression levels of CD41 might be increased compared to controls since the platelets are larger than control platelets. However, there was no overall increase in CD41 expression compared to PDS subjects. However, the ratio of normalized CD41 expression to CD42 expression in subjects with 22q11.2 deletion was inversely correlated with MPV (-0.31, p=.02) and was significantly lower than in other platelet disorders (5.2±0.6 vs 4.3±0.6, p<0.05). Bleeding manifestations were reported in 19/56 patients with 22qDS and of these 9/19 (47%) had low expression of CD42b and did not correlate with level of expression of CD42 (p NS). Taken together these data demonstrate that macro-thrombocytopenia (MPV >9, plt <150) with low expression of CD42 (<70% control) and high normalized CD41:CD42 ratio (>7), the diagnosis of 22q11.2 deletion syndrome results in a specificty of 85% to detect 22q11.2DS with a positive predictive value of 67% when at least 3 of the 4 criteria are present. We suggest that if subjects evaluated for thrombocytopenia manifest this constellation, appropriate genetic testing should be considered and sent, especially given that the manifestations of the disorder can be subtle, but the consequences for management are significant. Future studies will focus on prospectively evaluating all subjects with the combination of decreased CD42 expression, macrothrombocytopenia and low normalized CD42:CD41 ratio to see if this combination can predict the presence of 22q11.2 deletion. Disclosures No relevant conflicts of interest to declare.

scholarly journals CD4+ CD25+ T-Cell Production in Healthy Humans and in Patients with Thymic Hypoplasia

2002 ◽  
Vol 9 (5) ◽  
pp. 1129-1131 ◽  
Author(s):  
Kathleen E. Sullivan ◽  
Donna McDonald-McGinn ◽  
Elaine H. Zackai
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Healthy Children ◽  
22Q11.2 Deletion ◽  
Healthy Humans ◽  
Healthy Infants ◽  
Chromosome 22Q11.2 ◽  
Chromosome 22Q11.2 Deletion Syndrome

ABSTRACT Regulatory T cells are found primarily in the CD4+ CD25+ fraction of T cells and play an important role in the prevention of autoimmunity. We examined CD4+ CD25+ T cells in 33 healthy children and adults and compared them to a population with an inherited form of thymic hypoplasia and a predisposition to autoimmune disease. Absolute numbers of CD4+ CD25+ T cells were markedly higher in healthy infants than in infants with chromosome 22q11.2 deletion syndrome.

Surgical Management of Patients With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (5) ◽  
pp. 857-869
Author(s):  
Oksana A. Jackson ◽  
Alison E. Kaye
Keyword(s):  
Surgical Management ◽  
Preoperative Evaluation ◽  
Preoperative Assessment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Surgical Decision ◽  
Obstructive Sleep ◽  
Spine Abnormalities ◽  
Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (4) ◽  
pp. 633-640 ◽  
Author(s):  
Canice E. Crerand ◽  
Ari N. Rabkin
Keyword(s):  
Cognitive Abilities ◽  
Psychotic Disorders ◽  
Developmental Stages ◽  
Early Adulthood ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychosocial Risks ◽  
Empirically Supported ◽  
Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

Conotruncal heart defects and aortic arch anomalies in fetuses with 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
I.V. Novikova, O.M. Khurs, T.V. Demidovich et all
Keyword(s):  
Aortic Arch ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
Ventricular Outflow Tract ◽  
Double Outlet Right Ventricle ◽  
Interrupted Aortic Arch ◽  
Left Ventricular ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Aortic Arch Anomalies

16 second trimester fetuses with 22q11.2 deletion syndrome have been examined at anatomic-pathological investigation. Main cardiovascular diseases were ascending aorta hypoplasia with aortic valve stenosis (n = 6; 37.5%), truncus arteriosus (n = 5; 31.25%), tetralogy of Fallot (n = 3; 18.75%) and double-outlet right ventricle (n = 1; 6.25%). Ventricular septal defect was present in 16 cases. Associated aortic arch anomalies included interrupted aortic arch (n = 9; 56.25%), right aortic arch (n = 6; 37.5%), retroesophageal ring (n = 1; 6.25%) and aberrant right subclavian arteria (n = 5; 31.25%). 5 fetuses had left ventricular outflow tract obstructive lesions with interrupted aortic arch of type B combined with aberrant right subclavian arteria.

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