70 results on '"Zackai, Elaine"'
Search Results
2. Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome: A survey of practice patterns
- Author
-
Jackson, Oksana A., Paine, Kaitlyn, Magee, Leanne, Maguire, Meg Ann, Zackai, Elaine, McDonald-McGinn, Donna M., McCormack, Susan, and Solot, Cynthia
- Published
- 2019
- Full Text
- View/download PDF
3. Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome
- Author
-
Tang, Sunny X., Moberg, Paul J., Yi, James J., Wiemken, Andrew S., Dress, Erich M., Moore, Tyler M., Calkins, Monica E., McDonald-McGinn, Donna M., Zackai, Elaine H., Emanuel, Beverly S., Gur, Ruben C., Gur, Raquel E., and Turetsky, Bruce I.
- Published
- 2018
- Full Text
- View/download PDF
4. White matter microstructural deficits in 22q11.2 deletion syndrome
- Author
-
Roalf, David R., Eric Schmitt, J., Vandekar, Simon N., Satterthwaite, Theodore D., Shinohara, Russell T., Ruparel, Kosha, Elliott, Mark A., Prabhakaran, Karthik, McDonald-McGinn, Donna M., Zackai, Elaine H., Gur, Ruben C., Emanuel, Beverly S., and Gur, Raquel E.
- Published
- 2017
- Full Text
- View/download PDF
5. Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study
- Author
-
Mekori-Domachevsky, Ehud, Guri, Yael, Yi, James, Weisman, Omri, Calkins, Monica E., Tang, Sunny X., Gross, Raz, McDonald-McGinn, Donna M., Emanuel, Beverly S., Zackai, Elaine H., Zalsman, Gil, Weizman, Abraham, Gur, Ruben C., Gur, Raquel E., and Gothelf, Doron
- Published
- 2017
- Full Text
- View/download PDF
6. Association of airway abnormalities with 22q11.2 deletion syndrome
- Author
-
Sacca, Rosalba, Zur, Karen B., Crowley, T. Blaine, Zackai, Elaine H., Valverde, Kathleen D., and McDonald-McGinn, Donna M.
- Published
- 2017
- Full Text
- View/download PDF
7. Neurocognitive profile in psychotic versus nonpsychotic individuals with 22q11.2 deletion syndrome
- Author
-
Weinberger, Ronnie, Yi, James, Calkins, Monica, Guri, Yael, McDonald-McGinn, Donna M., Emanuel, Beverly S., Zackai, Elaine H., Ruparel, Kosha, Carmel, Miri, Michaelovsky, Elena, Weizman, Abraham, Gur, Ruben C., Gur, Raquel E., and Gothelf, Doron
- Published
- 2016
- Full Text
- View/download PDF
8. Genomic Contributors to Esophageal Atresia and Tracheoesophageal Fistula: A 12 Year Retrospective Review.
- Author
-
Wild, K. Taylor, Conlin, Laura, Blair, Justin, Manfredi, Michael, Hamilton, Thomas E., Muir, Amanda, Zackai, Elaine H., Nace, Gary, Partridge, Emily A., Devine, Matthew, Reynolds, Tom, Rintoul, Natalie E., Hedrick, Holly L., Spinner, Nancy, and Krantz, Ian D.
- Published
- 2024
- Full Text
- View/download PDF
9. A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction: the t(8;22)(q24.13; q11.21)
- Author
-
Sheridan, Molly B., Kato, Takema, Haldeman-Englert, Chad, Jalali, Reza, Milunsky, Jeff M., Zou, Ying, Klaes, Ruediger, Gimelli, Georgio, Gimelli, Stefania, Gemmill, Robert M., Drabkin, Harry A., Hacker, April M., Brown, Julia, Tomkins, David, Shaikh, Tamim H., Kurahashi, Hiroki, Zackai, Elaine H., and Emanuel, Beverly S.
- Subjects
Dysmorphology -- Research ,Meiosis -- Analysis ,Polymerase chain reaction -- Usage ,Translocation (Genetics) -- Analysis ,Biological sciences - Abstract
The study describes a syndrome characterized by extremity anomalies, mild dysmorphia, and intellectual impairment caused by 3:1 meiotic segregation of a previously unrecognized recurrent palindrome-mediated rearrangement, the t(8;22)(q11.21). PCR analysis of sperm DNA from healthy males shows that the t(8;22) arises de novo during gametogenesis in some individuals, suggesting palindrome-mediated translocation is a universal mechanism generating chromosomal rearrangements.
- Published
- 2010
10. Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations
- Author
-
Stankiewicz, Pawel, Sen, Partha, Bhatt, Samarth S., Storer, Mekayla, Xia, Zhilian, Bejjani, Bassem A., Ou, Zhishuo, Wiszniewska, Joanna, Driscoll, Daniel J., Bolivar, Juan, Bauer, Mislen, Zackai, Elaine H., McDonald-McGinn, Donna, Nowaczyk, Ma?gorzata M.J., Murray, Mitzi, Shaikh, Tamim H., Martin, Vicki, Tyreman, Matthew, Simonic, Ingrid, Willatt, Lionel, Paterson, Joan, Mehta, Sarju, Rajan, Diana, Fitzgerald, Tomas, Gribble, Susan, Prigmore, Elena, Patel, Ankita, Shaffer, Lisa G., Carter, Nigel P., Cheung, Sau Wai, Langston, Claire, and Shaw-Smith, Charles
- Subjects
Gene mutations -- Research ,Vascular resistance -- Genetic aspects ,Lung diseases -- Genetic aspects ,Polymerase chain reaction -- Usage ,Nucleotide sequencing -- Usage ,Genetic transcription -- Analysis ,Biological sciences - Abstract
A study was conducted to analyze the role of FOXF1 in human lung and intrinsic pulmonary vascular development by describing inactivating mutations in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Findings reveal that patients with deletions harboring FOXF1 genes have not only ACD/MPV but also distinct malformations.
- Published
- 2009
11. PCDH19-related epilepsy in a male with Klinefelter syndrome: Additional evidence supporting PCDH19 cellular interference disease mechanism
- Author
-
Romasko, Edward J., DeChene, Elizabeth T., Balciuniene, Jorune, Akgumus, Gozde T., Helbig, Ingo, Tarpinian, Jennifer M., Keena, Beth A., Vogiatzi, Maria G., Zackai, Elaine H., Izumi, Kosuke, Massey, Shavonne L., and Tayoun, Ahmad N. Abou
- Published
- 2018
- Full Text
- View/download PDF
12. Psychosis Risk In 22Q11.2 Deletion Syndrome: Findings From The Philadelphia Sample
- Author
-
Gur, Raquel, Yi, James, Tang, Sunny, Calkins, Monica, Moore, Tyler, Schmitt, James, McDonald-McGinn, Donna, Zackai, Elaine, Xie, Michael, Gur, Ruben, and Emanuel, Beverly
- Published
- 2017
- Full Text
- View/download PDF
13. Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome.
- Author
-
Diaz, Laura K., Gaynor, J. William, Koh, Shannon J., Ittenbach, Richard F., Gerdes, Marsha, Bernbaum, Judy C., Zackai, Elaine H., Clancy, Robert R., Rehman, Mohamed A., Pennington, Jeffrey W., Burnham, Nancy, Spray, Thomas L., and Nicolson, Susan C.
- Abstract
Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Methods Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Results Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores ( P 's < .05) alone and after adjusting for relevant covariates. Conclusions Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
14. The Genomics of Congenital Diaphragmatic Hernia: A 10-Year Retrospective Review.
- Author
-
Wild, K. Taylor, Schindewolf, Erica, Hedrick, Holly L., Rintoul, Natalie E., Hartman, Tiffiney, Gebb, Juliana, Moldenhauer, Julie S., Zackai, Elaine H., and Krantz, Ian D.
- Abstract
Objective: To evaluate genetic testing use in infants with congenital diaphragmatic hernia (CDH) over the past decade to better inform future practices and individualize prognostication and management.Study Design: A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children's Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed.Results: The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56).Conclusions: The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
15. Long-term follow-up of ocular findings in children with Stickler's syndrome
- Author
-
Wilson, Martin C., McDonald-McGinn, Donna M., Quinn, Graham E., Markowitz, Gary D., LaRossa, Donato, Pacuraru, Anca D., Zhu, Xiaosong, and Zackai, Elaine H.
- Subjects
Eye -- Refractive errors ,Cleft palate -- Complications ,Health - Published
- 1996
16. NEUROCOGNITIVE FUNCTIONING IN 22Q11.2 DELETION SYNDROME
- Author
-
Gur, Raquel E., Emanuel, Beverly S., Yi, James J., McDonald-McGinn, Donna M., Tang, Sunny X., Zackai, Elaine H.J., Whinna, Daneen, Souders, Margaret C., Calkins, Monica E., Kohler, Christian G., Savitt, Adam, and Gur, Ruben C.
- Published
- 2014
- Full Text
- View/download PDF
17. Molecular Mechanisms Contributing to the Etiology of Congenital Diaphragmatic Hernia: A Review and Novel Cases.
- Author
-
Katz, Olivia L., Wild, K. Taylor, McEldrew, Deborah, Kaur, Maninder, Raible, Sarah, Skraban, Cara M., Zackai, Elaine H., Medne, Livija, Izumi, Kosuke, Fortunato, Sierra, Weatherly, Jamila, Hartman, Tiffiney, Deppen, Paul, Blair, Justin, Devkota, Batsal, Schindler, Emma, Hedrick, Holly L., Peranteau, William, and Krantz, Ian D.
- Published
- 2022
- Full Text
- View/download PDF
18. Patient Genotypes Impact Survival After Surgery for Isolated Congenital Heart Disease.
- Author
-
Seung Kim, Daniel, Kim, Jerry H., Burt, Amber A., Crosslin, David R., Burnham, Nancy, McDonald-McGinn, Donna M., Zackai, Elaine H., Nicolson, Susan C., Spray, Thomas L., Stanaway, Ian B., Nickerson, Deborah A., Russell, Mark W., Hakonarson, Hakon, Gaynor, J. William, and Jarvik, Gail P.
- Abstract
Background. Survival after cardiac surgery in infancy requires adaptive responses from oxidative stress management and vascular regulation pathways. We tested the hypothesis that genetic variation in these pathways influences postoperative survival in nonsyndromic congenital heart disease children. Methods. This is an analysis of a cohort of nonsyndromic congenital heart disease patients who underwent cardiac surgery with cardiopulmonary bypass before 6 months of age (n = 422). Six single nucleotide polymorphisms (SNPs) in six genes involved in oxidative stress and vascular response pathways, identified through a priori literature search, were tested for effects on transplant-free survival. Survival curves, adjusting for confounding covariates, were calculated using the Cox proportional hazard models. Results. Long-term survival was strongly associated with vascular endothelial growth factor A gene SNP rs833069 (p = 7.03x10
-4 ) and superoxide dismutase gene SNP rs2758331 (p = 0.019). To test for joint effects of the two SNPs on transplant-free survival, the genotypes were grouped to form a risk score reflecting the cumulative number of risk alleles (0 to 4 alleles per patient). A higher risk score based on the VEGFA and SOD2 SNP genotypes was associated with worse transplant-free survival (p = 3.02x10-4 ) after confounder adjustment. The total burden of risk alleles was additive; subjects with the highest risk score of 4 (n = 59 subjects, 14.2% of the cohort) had a total covariate-adjusted hazard ratio of 15.64 for worse transplant-free survival. Conclusions. After cardiac surgery, infants who are homozygous for the high-risk alleles for both the VEGFA and SOD2 SNPs have an approximately 16-fold increased risk of death or heart transplant, suggesting that genetic variants are important modifiers of survival after surgery for congenital heart disease. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
19. Is cardiac diagnosis a predictor of neurodevelopmental outcome after cardiac surgery in infancy?
- Author
-
Gaynor, J. William, Gerdes, Marsha, Nord, Alex S., Bernbaum, Judy, Zackai, Elaine, Wernovsky, Gil, Clancy, Robert R., Heagerty, Patrick J., Solot, Cynthia B., McDonald-McGinn, Donna, and Jarvik, Gail P.
- Subjects
DEVELOPMENTAL neurobiology ,CARDIAC surgery ,INFANTS ,SURGERY ,CONGENITAL heart disease ,TETRALOGY of Fallot ,TRANSPOSITION of great vessels ,NEUROPSYCHOLOGICAL tests ,VENTRICULAR septal defects - Abstract
Objectives: To determine whether a cardiac diagnosis is a predictor of neurodevelopmental outcomes after infant cardiac surgery. Methods: Infants with ventricular septal defect (VSD), tetralogy of Fallot (TOF), transposition of the great arteries (TGA), and hypoplastic left heart syndrome (HLHS) in a study of apolipoprotein E (APOE) polymorphisms, and neurodevelopmental outcome underwent neurodevelopmental and genetic evaluation at 4 years of age. The domains tested included cognition, language, speech, memory, executive function, visual-motor, fine motor, and reading and math skills. Results: Testing was completed in 178 patients with normal genetic evaluations: VSD (n = 26), TOF (n = 44), TGA (n = 41), and HLHS (n = 67). No differences were found in gestational age, ethnicity, APOE genotype, socioeconomic status, or maternal education among groups. Patient age at the first surgery was significantly lower for patients with TGA and HLHS compared with those with TOF and VSD. The postoperative length of stay was significantly longer for HLHS than all other groups and for TGA compared with TOF and VSD. HLHS correlated significantly with the use of deep hypothermic circulatory arrest and multiple operations. The mean scores for each domain were within normal limits for all groups. Compared with the other patients, those with HLHS had significantly lower scores for cognition, fine motor skills, executive function, and math skills. No significant differences were found among the TGA, TOF or VSD patients for any domain. Significant impairments in at least 1 domain were identified in 8% (2/25) of patients with VSD, 20% (8/41) with TOF, 17% (7/41) with TGA, and 18% (12/65) with HLHS. After correction for the demographic, preoperative, and operative variables, no significant differences were found among the groups for any domain. Conclusions: The mean scores for the neurodevelopmental outcomes domains tested were in the normal range for preschool children with no recognized genetic syndromes after surgery for VSD, TOF, TGA, and HLHS. In each diagnostic group, the number of children with impairments in at least 1 domain increased compared with the general population. Unadjusted neurodevelopmental outcomes for HLHS were lower for cognition, fine motor skills, executive function, and math skills compared with the other patients. After correction for the demographic, preoperative, and operative variables, no significant differences were found among the groups for any domain. The specific cardiac diagnosis determines a large portion of the variation in these covariates. Therefore, although HLHS did predict for poorer outcomes in some domains, it did not add predictive power to the other factors considered. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
20. Genetic factors are important determinants of impaired growth after infant cardiac surgery.
- Author
-
Burnham, Nancy, Ittenbach, Richard F., Stallings, Virginia A., Gerdes, Marsha, Zackai, Elaine, Bernbaum, Judy, Clancy, Robert R., and Gaynor, J. William
- Subjects
CORONARY heart disease in children ,INFANT growth ,GENETIC polymorphisms ,APOLIPOPROTEIN E ,STANDARD deviations ,VENTRICULAR septal defects ,LONGITUDINAL method - Abstract
Objectives: We sought to estimate the prevalence and identify the predictors of impaired growth after infant cardiac surgery. Methods: We performed a secondary analysis of a prospective study of the role of apolipoprotein E gene polymorphisms on neurodevelopment in young children after infant cardiac surgery. Prevalence estimates for growth velocity were derived by using anthropometric measures (weight and head circumference) obtained at birth and at 4 years of age. Genetic evaluation was also performed. Growth measure z scores were calculated by using World Health Organization Child Growth Standards. Growth velocity was evaluated by using 2 different techniques: first by clustering the children into one of 3 growth velocity subgroups based on z scores (impaired growth, difference < −0.5 standard deviation; stable growth, difference of −0.5 to 0.5 standard deviation; and improving growth, difference > 0.5 SD) and second by using continuous difference scores. Statistical analyses were conducted with a combination of proportional odds models for the ordered categories and simple linear regression for the continuous outcomes. Results: Three hundred nineteen full-term subjects had complete anthropometric measures for weight and head circumference at birth and 4 years. The cohort was 56% male. Genetic examinations were available for 97% (309/319) of the cohort (normal, 74%; definite or suspected genetic abnormality, 26%). Frequency counts for weight categories were as follows: impaired growth, 37%; stable growth, 31%; and improving growth, 32%. Frequency counts for head circumference categories were as follows: impaired growth, 39%; stable growth, 28%; and improving growth, 33%. The presence of a definite or suspected genetic syndrome (P = .04) was found to be a predictor of impaired growth for weight but not for head circumference. When growth z scores were used as continuous outcomes, the apolipoprotein E ε2 allele was found to be predictive of lower z scores for both weight (P = .02) and head circumference (P = .03). Conclusions: Impaired growth for both weight and head circumference is common (both >30%) in this cohort of children after infant cardiac surgery. Both the apolipoprotein E ε2 allele and the presence of a definite or suspected genetic syndrome were associated with impaired weight growth velocity. The apolipoprotein E ε2 allele was also associated with impaired growth velocity for head circumference. Persistent poor growth might have long-term implications for the health and development of children with congenital heart defects. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF
21. Ocular findings associated with chromosome 22q11.2 duplication.
- Author
-
Forbes, Brian J., McDonald-McGinn, Donna M., Wootton, Georgia, Dawson, Lindsay, Zackai, Elaine, and Binenbaum, Gil
- Abstract
We describe the ocular features of the chromosome 22q11.2 duplication syndrome and provide ophthalmologic examination recommendations for affected patients. The medical records of 19 children with chromosome 22q11.2 duplication who had undergone complete ophthalmological examination, including dilated fundus examination and cycloplegic refraction, were studied retrospectively. Over half of the children with 22q11.2 duplication syndrome were found to have visually significant ocular abnormalities, including 6 with strabismus, 2 with moderately high astigmatism requiring glasses, 1 with unilateral congenital cataract requiring surgery, 1 with optic disk drusen, 1 with bilateral megalocornea with normal eye pressures, 1 with nystagmus that resolved spontaneously, and 1 with delayed visual maturation. Because of the high incidence of conditions that could affect visual development, we recommend that children with 22q11.2 duplication syndrome have a complete ophthalmological examination on diagnosis and regular vision screenings by their primary care physician thereafter. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
22. Genetic factors are important determinants of neurodevelopmental outcome after repair of tetralogy of Fallot.
- Author
-
Zeltser, Ilana, Jarvik, Gail P., Bernbaum, Judy, Wernovsky, Gil, Nord, Alex S., Gerdes, Marsha, Zackai, Elaine, Clancy, Robert, Nicolson, Susan C., Spray, Thomas L., and Gaynor, J. William
- Subjects
CONGENITAL heart disease ,HEART abnormalities ,GENETIC polymorphisms ,PULMONARY atresia - Abstract
Objective: Adverse neurodevelopmental sequelae are common in children with congenital heart defects. Tetralogy of Fallot is part of the clinical phenotype of many genetic syndromes. We evaluated the determinants of neurodevelopmental outcome in patients with tetralogy of Fallot. Methods: We performed a subgroup analysis of children with tetralogy of Fallot undergoing complete repair before 6 months of age who were enrolled in a trial assessing apolipoprotein E genotype as a predictor of neurodevelopmental outcome. Assessment included genetic evaluation, neurologic examination, and the Bayley Scales of Infant Development-II, yielding the Mental Developmental Index and Psychomotor Developmental Index. Results: Sixty children were tested at 1 year of age. A confirmed or suspected genetic syndrome was identified in 18.3%. The mean Mental Developmental Index was 89 ± 13, and the mean Psychomotor Developmental Index was 81 ± 17. Scores for the Mental Developmental Index (76 ± 13 vs 92 ± 11) and Psychomotor Developmental Index (63 ± 13 vs 85 ± 15) were significantly lower for patients with genetic syndromes. The presence of a genetic syndrome was a predictor of lower Mental Developmental Index and Psychomotor Developmental Index (P = .002 and P = .001). The presence of tetralogy of Fallot with pulmonary atresia and the apolipoprotein E ε2 allele were predictive of a lower Mental Developmental Index (P = .001 and P = .035). No other preoperative or operative variables were predictive of worse neurodevelopmental outcome. Conclusions: At 1 year of age after repair of tetralogy of Fallot, most patients had neurodevelopmental scores within the normal range. Genetic syndromes and the apolipoprotein E ε2 allele were important risk factors for neurodevelopmental dysfunction and accounted for some interindividual differences in outcome. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
23. Hyperglycemia After Infant Cardiac Surgery Does Not Adversely Impact Neurodevelopmental Outcome.
- Author
-
Ballweg, Jean A., Wernovsky, Gil, Ittenbach, Richard F., Bernbaum, Judy, Gerdes, Marsha, Gallagher, Paul R., Dominguez, Troy E., Zackai, Elaine, Clancy, Robert R., Nicolson, Susan C., Spray, Thomas L., and Gaynor, J. William
- Subjects
HYPERGLYCEMIA ,CARDIAC surgery ,GENETIC polymorphisms ,BRAIN injuries - Abstract
Background: Hyperglycemia has been associated with worse outcome after traumatic brain injury and cardiac surgery in adults. It is not known whether postoperative hyperglycemia results in worse neurodevelopmental outcome after infant cardiac surgery. Methods: Secondary analysis of postoperative glucose levels was performed in infants younger than 6 months of age enrolled in a prospective study of genetic polymorphisms and neurodevelopmental outcomes who were undergoing repair of two-ventricle cardiac defects. Neurodevelopmental outcomes at 1 year of age were assessed with the Bayley Scales of Infant Development-II, yielding two indices: Mental Developmental Index and Psychomotor Developmental Index. Results: Surgical repair was performed in 247 infants with 1 in-hospital and 3 late deaths. Neurodevelopmental evaluation was performed in 188 of 243 (77%) survivors. Glucose levels at cardiac intensive care unit admission and during the first 48 postoperative hours were available for 180 of 188 patients. Mean admission glucose was 328 ± 106 mg/dL; maximum glucose was 340 ± 109 mg/dL. At least one glucose was greater than 200 mg/dL in 160 of 180 patients, and 49 of 180 patients (27%) had a glucose greater than 400 mg/dL. Only 1 patient had a glucose less than 50 mg/dL. Female sex (p = 0.02), but no other patient or operative variable, was associated with higher glucose levels. Mean Mental Developmental Index and Psychomotor Developmental Index were 90.6 ± 14.9 and 81.6 ± 17.2, respectively. Hyperglycemia was not associated with lower Mental Developmental Index and Psychomotor Developmental Index scores for the entire cohort or for neonates alone. Conclusions: Hyperglycemia is common early after infant cardiac surgery, but is not associated with worse neurodevelopmental outcome at 1 year of age. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
24. Patient characteristics are important determinants of neurodevelopmental outcome at one year of age after neonatal and infant cardiac surgery.
- Author
-
Gaynor, J. William, Wernovsky, Gil, Jarvik, Gail P., Bernbaum, Judy, Gerdes, Marsha, Zackai, Elaine, Nord, Alex S., Clancy, Robert R., Nicolson, Susan C., and Spray, Thomas L.
- Subjects
NEURODEVELOPMENTAL treatment ,OCCUPATIONAL therapy ,CARDIAC surgery ,PREOPERATIVE risk factors - Abstract
Objective: Many studies of neurodevelopmental outcomes after neonatal and infant cardiac surgery have focused on potentially modifiable risk factors for adverse outcomes, primarily intraoperative management strategies and the use of deep hypothermic circulatory arrest. There is increasing evidence that patient-specific factors are more important determinants of outcome. Methods: We investigated predictors of neurodevelopmental outcomes at 1 year of age after neonatal and infant cardiac surgery in a subgroup of infants enrolled in a prospective study of apolipoprotein E (APOE) genotype and neurodevelopmental outcome. Children with a variety of 2-ventricle cardiac defects repaired with only 1 operation with cardiopulmonary bypass and no more than 1 episode of deep hypothermic circulatory arrest were included. Neurodevelopmental outcomes at 1 year of age included the Bayley Scales of Infant Development-II, which yield 2 indices, the Mental Developmental Index and the Psychomotor Developmental Index. Results: Two hundred forty-seven infants underwent surgical repair between October 1998 and April 2003 with 1 hospital death and 3 deaths before 1 year of age. Neurodevelopmental evaluation was performed in 188 (77%) of 243 survivors, including 56 patients with tetralogy of Fallot, 39 with transposition of the great arteries with intact ventricular septum, 34 with ventricular septal defects, and 59 with other defects. The median age at operation was 56 days (1–186 days), including 72 (38%) neonates. Confirmed or suspected genetic syndromes were present in 59 (31%) of 188 infants. Deep hypothermic circulatory arrest was used in 67 (35%) infants with a median duration of 34 minutes (1-80 minutes). For the entire cohort, the mean Mental Developmental Index was 90.6 ± 14.9 and the mean Psychomotor Developmental Index was 81.6 ± 17.2. For patients without genetic syndromes, the mean Mental Developmental Index was 93.7 ± 13.6 and the mean Psychomotor Developmental Index was 85.1 ± 14.6. For the entire cohort, predictors of lower scores for both the Mental Developmental Index and Psychomotor Developmental Index were presence of a confirmed or suspected genetic syndrome, lower birth weight, and presence of the APOE ϵ2 allele (all P < .04). Black race was associated with higher scores on the Psychomotor Developmental Index (P = .018). Lower nasopharyngeal temperature during cardiopulmonary bypass was associated with a lower score on the Psychomotor Developmental Index (P = .03) and was the only intraoperative factor that was a significant predictor of either the Mental or Psychomotor Developmental Index. Conclusions: The strongest predictors of a worse neurodevelopmental outcome at 1 year of age were patient-specific factors including presence of a genetic syndrome, low birth weight, and presence of the APOE ϵ2 allele. Patient-specific factors eclipsed the use and duration of deep hypothermic circulatory arrest as predictors of worse neurodevelopmental outcomes. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
25. Ocular findings in the chromosome 22q11.2 deletion syndrome.
- Author
-
Forbes, Brian J., Binenbaum, Gil, Edmond, Jane C., DeLarato, Nicole, McDonald-McGinn, Donna M., and Zackai, Elaine H.
- Subjects
CHROMOSOME abnormalities ,EYE examination ,STRABISMUS ,PATIENTS - Abstract
Purpose: To identify the ocular features of the chromosome 22q11.2 deletion syndrome and to provide ophthalmologic examination recommendations for affected patients. Methods: Ocular abnormalities were evaluated prospectively in patients with 22q11.2 deletion at the Children’s Hospital of Philadelphia between 1997 and 1999. Results: Ninety patients with confirmed 22q11.2 deletion were examined. Posterior embryotoxon was found in 49%, tortuous retinal vessels in 34%, eyelid hooding in 20%, strabismus in 18%, ptosis in 4%, amblyopia in 4%, and tilted optic nerves in 1%. Conclusions: The high incidence of ocular conditions that can potentially affect visual development suggest that children with 22q11.2 deletion should undergo a comprehensive eye examination upon diagnosis of the condition with follow-up as indicated by the findings in each case. In addition, knowledge of the ocular findings, in conjunction with certain cardiac, otolaryngologic, immunologic, and other systemic findings, may alert physicians to the possibility of a chromosome 22q11.2 deletion. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
26. Ocular abnormalities in Apert syndrome: Genotype/phenotype correlations with fibroblast growth factor receptor type 2 mutations.
- Author
-
Jadico, Suzanne K., Young, David A., Huebner, Alexandra, Edmond, Jane C., Pollock, Avrum N., McDonald-McGinn, Donna M., Li, Yi-Ju, Zackai, Elaine H., and Young, Terri L.
- Subjects
GENETIC research ,AMBLYOPIA ,VISION disorders ,MYOPIA - Abstract
Background/Purpose: Apert syndrome, a disorder of craniosynostosis, syndactyly, and other craniofacial malformations, is caused by point mutations (Ser252Trp or Pro253Arg) in the fibroblast growth factor receptor 2 gene. This study’s goal was to determine ophthalmic phenotype/genotype correlations in patients with either mutation. Methods: A retrospective chart review of demographic and ophthalmologic data was performed for 18 children carrying either the S252W (11) or the P253R (7) mutation. Fisher exact tests were performed to determine significance of variable phenotypes between the two mutation groups. Results: In the P253R group, 85% had strabismus (14% required surgery), 71% had ptosis, 43% had amblyopia, 14% had nasolacrimal duct obstruction, 14% had myopia, 14% had hyperopia, and 14% had astigmatism. In the S252W group, 91% had strabismus (64% required surgery), 73% had ptosis, 73% had amblyopia, 100% had nasolacrimal duct obstruction, 36% had myopia, 9% had hyperopia, and 82% had astigmatism. Overall, S252W and P253R groups showed significantly different numbers of patients with strabismus requiring surgery (p = 0.039), superior rectus muscle underaction (p = 0.024), nasolacrimal duct obstruction (p = 0.0002), and astigmatism (p = 0.005). Conclusions: Compared with patients with the P253R mutation, Apert syndrome patients with the S252W mutation may have more severe ocular phenotypes with a higher likelihood of developing strabismus, especially vertical deviation. They also are more likely to develop astigmatic refractive errors and tearing secondary to nasolacrimal system anomalies. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
27. Ocular Phenotype Correlations in Patients with TWIST Versus FGFR3 Genetic Mutations.
- Author
-
Jadico, Suzanne K., Huebner, Alexandra, McDonald-McGinn, Donna M., Zackai, Elaine H., and Young, Terri L.
- Subjects
EYE movement disorders ,STRABISMUS surgery ,ASTIGMATISM ,HYPEROPIA - Abstract
Background/purpose: Despite the similar clinical phenotype of the Saethre-Chotzen and Muenke craniosynostoses, the 2 syndromes are now genotypically distinct. Patients with Saethre-Chotzen and Muenke syndromes carry mutations in the TWIST and fibroblast growth factor receptor (FGFR) 3 genes, respectively. We sought to assess possible ocular phenotypic differences in patients with mutations of either gene previously grouped according to phenotype only. Methods: A retrospective chart review was performed for 21 children with known mutations of the TWIST (n=10) or the FGFR3 (n=11) genes. Data gathered included patient sex, age, family craniofacial history, craniofacial and ophthalmic surgeries, type of strabismus, ptosis, cycloplegic refraction, visual acuity, the presence of amblyopia, nasolacrimal duct obstruction (NLDO), nystagmus, hypertelorism, epicanthal fold anomalies, and any ocular structural abnormalities. Results: In the TWIST group, ptosis was present in 90%, amblyopia in 70%, horizontal strabismus in 70%, vertical strabismus in 60%, NLDO in 60%, astigmatism in 50%, inferior oblique overaction (IOOA) in 40%, hyperopia in 40%, myopia in 30%, nystagmus in 30%, and optic nerve findings in 30%. In the FGFR3 group, ptosis was present in 36%, amblyopia in 18%, horizontal strabismus in 55%, vertical strabismus in 36%, NLDO in 0%, astigmatism in 9%, IOOA in 45%, hyperopia in 27%, myopia in 18%, nystagmus in 18%, and optic nerve findings in 27%. Conclusions: Patients with TWIST gene mutations may have more ophthalmic abnormalities, including more strabismus, ptosis, NLDO, astigmatism, vertical deviations, and amblyopia compared with patients with FGFR3 gene mutations. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
28. Neurodevelopmental outcome after early repair of a ventricular septal defect with or without aortic arch obstruction.
- Author
-
Kaltman, Jonathan R., Jarvik, Gail P., Bernbaum, Judy, Wernovsky, Gil, Gerdes, Marsha, Zackai, Elaine, Clancy, Robert R., Nicolson, Susan C., Spray, Thomas L., and Gaynor, J. William
- Subjects
NEURODEVELOPMENTAL treatment ,NEUROLOGICAL disorders ,DISABILITIES ,CHILD development testing - Abstract
Objectives: Cross-sectional studies of intermediate-term survivors of infant cardiac surgery have revealed a high frequency of neurodevelopmental disabilities. Few data exist regarding neurodevelopmental outcome of infants undergoing surgical intervention for a ventricular septal defect. The purpose of this study was to evaluate the neurodevelopmental outcome at 1 year of age of children who had surgical repair in infancy of a ventricular septal defect or a ventricular septal defect with aortic arch obstruction. Methods: Children who underwent repair of a ventricular septal defect or single-stage repair of a ventricular septal defect with aortic arch obstruction at less than 6 months of age were assessed at 1 year of age by using the Bayley Scales of Infant Development II, which yields the Mental Development Index and the Psychomotor Development Index, both with an expected mean of 100 ± 15. Results: At 1 year, 55 patients (ventricular septal defect alone = 36; ventricular septal defect with aortic arch obstruction = 19) returned for evaluation. The mean Mental Development Index was 92.6 ± 11.7, with 3 (5%) patients scoring 70 or less. The mean Psychomotor Development Index was 86.1 ± 16.4, with 10 (18%) patients scoring 70 or less. Patients with a suspected or confirmed genetic syndrome had both a lower Mental Development Index score (P = .011) and a lower Psychomotor Development Index score (P = .001). Mental Development Index and Psychomotor Development Index were independent of anatomic (specifically aortic arch obstruction) and intraoperative factors (specifically deep hypothermic circulatory arrest). Conclusions: Neurodevelopmental outcome at 1 year of age was within the normal limits for most patients who underwent repair of a ventricular septal defect or a ventricular septal defect with aortic arch obstruction during infancy. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
29. The relationship of postoperative electrographic seizures to neurodevelopmental outcome at 1 year of age after neonatal and infant cardiac surgery.
- Author
-
Gaynor, J. William, Jarvik, Gail P., Bernbaum, Judy, Gerdes, Marsha, Wernovsky, Gil, Burnham, Nancy B., D’Agostino, Jo Ann, Zackai, Elaine, McDonald-McGinn, Donna M., Nicolson, Susan C., Spray, Thomas L., and Clancy, Robert R.
- Subjects
CONGENITAL heart disease ,CARDIAC surgery & psychology ,NEWBORN infants ,BAYLEY Scales of Infant Development - Abstract
Objective: The occurrence of a seizure after the arterial switch operation is associated with a worse long-term neurodevelopmental outcome. The significance of seizures after neonatal and infant repair of other congenital heart defects is not known. Methods: A recent study at our institution demonstrated seizures documented by 48-hour electroencephalographic monitoring in 20 (11%) of 178 neonates and infants after surgery for complex congenital heart defects, including hypoplastic left heart syndrome or variants. The developmental outcomes of this cohort were evaluated at 1 year of age by using the Bayley Scales of Infant Development II, which yields 2 scores: the Mental Developmental Index and the Psychomotor Developmental Index. Results: Developmental evaluations were performed in 114 (70%) of 164 survivors, including 36 with hypoplastic left heart syndrome. Postoperative electroencephalographic seizures had occurred in 15 (13%) of 114 of the entire group and in 8 (22%) of 36 of those with hypoplastic left heart syndrome. For the entire cohort, the Mental Developmental Index was 92.3 ± 13.5, and the Psychomotor Developmental Index was 79.9 ± 18.8 for patients without seizures, compared with 90.3 ± 10.7 and 74.4 ± 19.3 for those with seizures (both P > .5). For the hypoplastic left heart syndrome subgroup, the Mental Developmental Index was 92.3 ± 14.9, and the Psychomotor Developmental Index was 74.8 ± 19.3 for patients with seizures, compared with 91.9 ± 12.4 and 73.9 ± 18.3 for those without seizures (both P > .5). A frontal onset of seizures was predictive of a lower score on the Psychomotor Developmental Index, but not on the Mental Developmental Index. Conclusions: The occurrence of a seizure after cardiac operation is a marker of central nervous system injury. However, in this cohort of neonates and infants with complex congenital heart defects, the occurrence of a seizure was not predictive of a worse developmental outcome at 1 year of age as assessed by the Bayley Scales of Infant Development II. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
30. Effect of congenital heart disease on neurodevelopmental outcomes within multiple-gestation births.
- Author
-
Schultz, Amy H., Jarvik, Gail P., Wernovsky, Gil, Bernbaum, Judy, Clancy, Robert R., D'Agostino, Jo Ann, Gerdes, Marsha, McDonald-McGinn, Donna, Nicolson, Susan C., Spray, Thomas L., Zackai, Elaine, and Gaynor, J. William
- Subjects
HEART diseases ,CONGENITAL heart disease ,CARDIOLOGY ,CARDIAC surgery - Abstract
Objectives: We sought to assess the effect of congenital heart disease requiring surgical intervention with cardiopulmonary bypass at 6 months of age or less on developmental outcomes and growth at 1 year of age while controlling for socioeconomic status, prematurity, home environment, and parental intelligence. Methods: We performed within-family comparison of 11 multiple-gestation births in which one child had congenital heart disease. At 1 year of age, the Bayley Scales of Infant Development II were administered, and growth parameters were assessed. Paired comparisons were made by using fixed effects regression conditioned on family. Results: The multiple-gestation subjects were mildly premature on average (mean gestational age, 35.4 ± 3.0 weeks). At 1 year of age, children with congenital heart disease scored lower on the Mental Development Index (85.0 ± 19.3 vs 93.9 ± 16.0, P = .037) and the Psychomotor Development Index (76.6 ± 16.9 vs 91.3 ± 14.9, P = .015) on the Bayley Scales of Infant Development II than did their siblings without congenital heart disease. There were no differences between siblings in weight, height, or head circumference. Conclusions: The presence of congenital heart disease requiring surgical intervention with cardiopulmonary bypass at 6 months of age or less is associated with a deficit in developmental achievement at 1 year of age, as measured by using the Bayley Scales of Infant Development II. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
31. Autosomal dominant mannose-binding lectin deficiency is associated with worse neurodevelopmental outcomes after cardiac surgery in infants.
- Author
-
Kim, Daniel Seung, Li, Yatong K., Kim, Jerry H., Bergquist, Curtis S., Gerdes, Marsha, Bernbaum, Judy C., Burnham, Nancy, McDonald-McGinn, Donna M., Zackai, Elaine H., Nicolson, Susan C., Spray, Thomas L., Nickerson, Deborah A., Hakonarson, Hakon, Jarvik, Gail P., and Gaynor, J. William
- Abstract
Objectives The MBL2 gene is the major genetic determinant of mannose-binding lectin (MBL)—an acute phase reactant. Low MBL levels have been associated with adverse outcomes in preterm infants. The MBL2 Gly54Asp missense variant causes autosomal dominant MBL deficiency. We tested the hypothesis that MBL2 Gly54Asp is associated with worse neurodevelopmental outcomes after cardiac surgery in neonates. Methods This is an analysis of a previously described cohort of patients with nonsyndromic congenital heart disease who underwent cardiac surgery with cardiopulmonary bypass before age 6 months (n = 295). Four-year neurodevelopment was assessed in 3 domains: Full-Scale Intellectual Quotient, the Visual Motor Integration development test, and the Child Behavior Checklist to assess behavior problems. The Child Behavior Checklist measured total behavior problems, pervasive developmental problems, and internalizing/externalizing problems. A multivariable linear regression model, adjusting for confounders, was fit. Results MBL2 Gly54Asp was associated with a significantly increased covariate-adjusted pervasive developmental problem score (β = 3.98; P = .0025). Sensitivity analyses of the interaction between age at first surgery and MBL genotype suggested effect modification for the patients with MBL2 Gly54Asp ( P interaction = .039), with the poorest neurodevelopment outcomes occurring in children who had surgery earlier in life. Conclusions We report the novel finding that carriers of MBL2 Gly54Asp causing autosomal dominant MBL deficiency have increased childhood pervasive developmental problems after cardiac surgery, independent of other covariates. Sensitivity analyses suggest that this effect may be larger in children who underwent surgery at earlier ages. These data support the role of nonsyndromic genetic variation in determining postsurgical neurodevelopment-related outcomes in children with congenital heart disease. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
32. Hearing Loss after Cardiac Surgery in Infancy: An Unintended Consequence of Life-Saving Care.
- Author
-
Grasty, Madison A, Ittenbach, Richard F, Knightly, Carol, Solot, Cynthia B, Gerdes, Marsha, Bernbaum, Judy C, Wernovsky, Gil, Spray, Thomas L, Nicolson, Susan C, Clancy, Robert R, Licht, Daniel J, Zackai, Elaine, Gaynor, J William, and Burnham, Nancy B
- Abstract
Objectives: To investigate the prevalence of hearing loss after cardiac surgery in infancy, patient and operative factors associated with hearing loss, and the relationship of hearing loss to neurodevelopmental outcomes.Study Design: Audiologic and neurodevelopmental evaluations were conducted on 348 children who underwent repair of congenital heart disease at the Children's Hospital of Philadelphia as part of a prospective study evaluating neurodevelopmental outcomes at 4 years of age. A prevalence estimate was calculated based on presence and type of hearing loss. Potential risk factors and the impact of hearing loss on neurodevelopmental outcomes were evaluated.Results: The prevalence of hearing loss was 21.6% (95% CI, 17.2-25.9). The prevalence of conductive hearing loss, sensorineural hearing loss, and indeterminate hearing loss were 12.4% (95% CI, 8.8-16.0), 6.9% (95% CI, 4.1-9.7), and 2.3% (95% CI, 0.6-4.0), respectively. Only 18 of 348 subjects (5.2%) had screened positive for hearing loss before this study and 10 used a hearing aid. After adjusting for patient and operative covariates, younger gestational age, longer postoperative duration of stay, and a confirmed genetic anomaly were associated with hearing loss (all P < .01). The presence of hearing loss was associated with worse language, cognition and attention (P <.01).Conclusions: These findings suggest that the prevalence of hearing loss in preschool children after heart surgery in infancy may be 20-fold higher than in the 1% prevalence seen in the general population. Younger gestational age, presence of a genetic anomaly, and longer postoperative duration of stay were associated with hearing loss. Hearing loss was associated with worse neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
33. Effect of congenital heart disease on 4-year neurodevelopment within multiple-gestation births.
- Author
-
Schultz, Amy H., Ittenbach, Richard F., Gerdes, Marsha, Jarvik, Gail P., Wernovsky, Gil, Bernbaum, Judy, Solot, Cynthia, Clancy, Robert R., Nicolson, Susan C., Spray, Thomas L., McDonald-McGinn, Donna, Zackai, Elaine, and Gaynor, J. William
- Abstract
Objectives We sought to assess the effect of congenital heart disease requiring infant surgery with cardiopulmonary bypass on neurodevelopmental outcomes and growth at 4 years of age, while matching for gestational age, socioeconomic status, maternal gestational conditions, home environment, and parental intelligence by studying multiple-gestation births. Methods We performed within-family comparison of 14 multiple-gestation births in which 1 child had congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age. Between 4 and 5 years of age, a comprehensive neurodevelopmental assessment was performed. Paired comparisons were conducted between siblings with and without heart defects using a series of nonparametric tests. Results On average, the children qualified as late preterm (mean gestational age 35.4 ± 2.6 weeks). At an average age of 4.8 ± 0.1 years, children with congenital heart disease weighed less than their siblings (median weight for age z score −0.4 vs 0.1, P = .02) and had worse performance for cognition (median full-scale IQ 99 vs 109, P = .02) and fine motor skills (median Wide Range Assessment of Visual Motor Ability, Fine Motor score 94.5 vs 107.5, P < .01). Conclusions After controlling for socioeconomic status, home environment, parental intelligence, and gestational factors by using multiple-gestation births, congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age is associated with lower weight, cognitive abilities and fine motor skills at 4 years of age. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
34. Burden of potentially pathologic copy number variants is higher in children with isolated congenital heart disease and significantly impairs covariate-adjusted transplant-free survival.
- Author
-
Kim, Daniel Seung, Kim, Jerry H., Burt, Amber A., Crosslin, David R., Burnham, Nancy, Kim, Cecilia E., McDonald-McGinn, Donna M., Zackai, Elaine H., Nicolson, Susan C., Spray, Thomas L., Stanaway, Ian B., Nickerson, Deborah A., Heagerty, Patrick J., Hakonarson, Hakon, Gaynor, J. William, and Jarvik, Gail P.
- Abstract
Objectives Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival. Methods These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival. Results Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment. Conclusions We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
35. Neurodevelopmental outcomes in preschool survivors of the Fontan procedure.
- Author
-
Gaynor, J. William, Ittenbach, Richard F., Gerdes, Marsha, Bernbaum, Judy, Clancy, Robert R., McDonald-McGinn, Donna M., Zackai, Elaine H., Wernovsky, Gil, Nicolson, Susan C., and Spray, Thomas L.
- Abstract
Objectives: The study objectives were to compare the neurodevelopmental outcomes of preschool survivors of the Fontan procedure with those of children with congenital heart disease undergoing biventricular repair and to investigate predictors of neurodevelopmental outcome for those with single ventricle congenital heart disease, including hypoplastic left heart syndrome. Methods: Neurodevelopmental outcomes were assessed at 4 years of age, including cognition, visual–motor integration, behavior, social skills, and academic achievement. Unadjusted outcomes were compared between patients with biventricular circulation and patients with single ventricles. Predictors of neurodevelopmental outcome were assessed in the patients with single ventricles. Multiple covariate models were evaluated using patient-related, operative, and postoperative covariates. Results: Neurodevelopmental evaluation was performed in 365 children, 112 after the Fontan procedure (hypoplastic left heart syndrome, n = 91; other single ventricle, n = 21) and 253 after biventricular repair. Compared with patients with biventricular circulation, patients with single ventricles performed worse in terms of processing speed, inattention, and impulsivity. Otherwise, there were no significant differences between the groups for any domain. There was a trend toward lower performance for patients with single ventricles on visual motor integration. Outcomes for patients with hypoplastic left heart syndrome were not worse than for other forms of functional single ventricle. Patient factors were more important predictors of neurodevelopmental outcomes than were operative management variables. Conclusions: In this cohort, unadjusted neurodevelopmental outcomes for preschool survivors of the Fontan procedure are similar to those for children with congenital heart disease undergoing biventricular repair for most domains. Among the patients undergoing the Fontan procedure, hypoplastic left heart syndrome was not associated with worse outcomes compared with other forms of single ventricle. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
36. A binational study assessing risk and resilience factors in 22q11.2 deletion syndrome.
- Author
-
Gur, Raquel E., White, Lauren K., Shani, Shachar, Barzilay, Ran, Moore, Tyler M., Emanuel, Beverly S., Zackai, Elaine H., McDonald-McGinn, Donna M., Matalon, Noam, Weinberger, Ronnie, Gur, Ruben C., and Gothelf, Doron
- Subjects
- *
22Q11 deletion syndrome , *EMOTIONS , *NEUROBEHAVIORAL disorders , *SYNDROMES , *PHENOTYPES , *APATHY , *SELF-reliance - Abstract
The presentation of neurogenetic disorders such as 22q11.2 Deletion Syndrome (22q11.2DS) includes broad neuropsychiatric phenotypes that impact functioning and require assessment and treatment. Like in non-syndromal neuropsychiatric disorders, there is heterogeneity in symptom severity and illness course. The study of risk and resilience in the general population has benefited from measurement tools that parse heterogeneity and guide treatment. Suitability of such tools in neurogenetic disorders has not been examined and is essential to establish as prerequisite for examining whether similar processes modulate psychopathology in these populations. We applied the Risk & Resilience Battery assessing intrapersonal, interpersonal, and environmental domains, to 80 patients with 22q11.2DS, 30 from Philadelphia, USA and 50 from Tel-Aviv, Israel. We also evaluated global functioning and obtained self-reports of anxiety and depression. We examined the Risk & Resilience Battery reliability for each factor and used partial correlations to examine relations between the Risk & Resilience Battery factors and clinical measures. Across samples, items within each risk and resilience factor showed good to excellent internal consistency. Higher scores on peer victimization, emotion dysregulation, and hostile close relationships were related to reports of anxiety and depression. Higher levels of self-reliance related to lower anxiety while greater security in close relationships related to lower depression. The Risk & Resilience Battery can be applied to 22q11.2DS samples and advance Gene X Environment research and interventions. • Risk and Resilience factors in the general population are similarly prominent in a neurogenetic syndrome. • These Risk and Resilience factors modulate symptom severity and functioning in a neurogenetic syndrome. • The Risk and Resilience measures can be reliably applied across international sites. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. Primary lymphedema and other lymphatic anomalies are associated with 22q11.2 deletion syndrome.
- Author
-
Unolt, Marta, Barry, Jessica, Digilio, Maria Cristina, Marino, Bruno, Bassett, Anne, Oechslin, Erwin, Low, David W., Belasco, Jean B., Kallish, Staci, Sullivan, Kathleen, Zackai, Elaine H., and McDonald–McGinn, Donna M.
- Subjects
- *
LYMPHEDEMA , *DELETION mutation , *LABORATORIES , *VASCULAR endothelial growth factor receptors , *IMAGING systems - Abstract
Background Lymphedema is an abnormal accumulation of interstitial fluid within the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it has been historically classified based on age at presentation. Although most cases are sporadic, primary lymphedema may be familial or present in association with chromosomal abnormalities and syndromic disorders. To the best of our knowledge, primary lymphedema has never been described in patients with 22q11.2 deletion syndrome. Methods and results We identified 4 patients with 22q11.2 deletion syndrome and primary lymphedema via our International 22q11.2 Deletion Syndrome Consortium. All patients underwent comprehensive clinical, laboratory and imaging assessments to rule out other causes of lymphedema. All patients had de novo typical deletions and family histories were negative for lymphedema. Conclusions We report the novel association of primary lymphedema with 22q11.2 deletion syndrome. Importantly, animal models demonstrated Tbx1 playing a critical role in lymphangiogenesis by reducing Vegfr3 expression in lymphatic endothelial cells. Moreover, the VEGFR3 pathway is essential for lymphangiogenesis with mutations identified in hereditary primary lymphedema. Accordingly, our findings provide a new insight into understanding cellular mechanisms of lymphangiogenesis disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
38. Impairment of different protein domains causes variable clinical presentation within Pitt-Hopkins syndrome and suggests intragenic molecular syndromology of TCF4.
- Author
-
Bedeschi, Maria Francesca, Marangi, Giuseppe, Calvello, Maria Rosaria, Ricciardi, Stefania, Leone, Francesca Pia Chiara, Baccarin, Marco, Guerneri, Silvana, Orteschi, Daniela, Murdolo, Marina, Lattante, Serena, Frangella, Silvia, Keena, Beth, Harr, Margaret H., Zackai, Elaine, and Zollino, Marcella
- Subjects
- *
DEVELOPMENTAL delay , *DELETION mutation , *EXONS (Genetics) , *NOSOLOGY , *PHENOTYPES - Abstract
Pitt-Hopkins syndrome is a neurodevelopmental disorder characterized by severe intellectual disability and a distinctive facial gestalt. It is caused by haploinsufficiency of the TCF4 gene. The TCF4 protein has different functional domains, with the NLS (nuclear localization signal) domain coded by exons 7–8 and the bHLH (basic Helix-Loop-Helix) domain coded by exon 18. Several alternatively spliced TCF4 variants have been described, allowing for translation of variable protein isoforms. Typical PTHS patients have impairment of at least the bHLH domain. To which extent impairment of the remaining domains contributes to the final phenotype is not clear. There is recent evidence that certain loss-of-function variants disrupting TCF4 are associated with mild ID, but not with typical PTHS. We describe a frameshift-causing partial gene deletion encompassing exons 4–6 of TCF4 in an adult patient with mild ID and nonspecific facial dysmorphisms but without the typical features of PTHS, and a c.520C > T nonsense variant within exon 8 in a child presenting with a severe phenotype largely mimicking PTHS, but lacking the typical facial dysmorphism. Investigation on mRNA, along with literature review, led us to suggest a preliminary phenotypic map of loss-of-function variants affecting TCF4 . An intragenic phenotypic map of loss-of-function variants in TCF4 is suggested here for the first time: variants within exons 1–4 and exons 4–6 give rise to a recurrent phenotype with mild ID not in the spectrum of Pitt-Hopkins syndrome (biallelic preservation of both the NLS and bHLH domains); variants within exons 7–8 cause a severe phenotype resembling PTHS but in absence of the typical facial dysmorphism (impairment limited to the NLS domain); variants within exons 9–19 cause typical Pitt-Hopkins syndrome (impairment of at least the bHLH domain). Understanding the TCF4 molecular syndromology can allow for proper nosology in the current era of whole genomic investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
39. The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.
- Author
-
Niarchou, Maria, Moore, Tyler M., Tang, Sunny X., Calkins, Monica E., McDonald-McGuinn, Donna M., Zackai, Elaine H., Emanuel, Beverly S., Gur, Ruben C., and Gur, Raquel E.
- Subjects
- *
PATHOLOGICAL psychology , *SUICIDE risk factors , *SUICIDE prevention , *NEUROLOGY , *ANESTHESIA in neurology - Abstract
Background 22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. Methods We evaluated 331 individuals with 22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). Results Psychopathology in 22q11.2DS was divided into one ‘general psychopathology’ factor and four specific dimensions (i.e., ‘anxiety’, ‘mood’, ‘ADHD’ and ‘psychosis’). The ‘psychosis’ symptoms loaded strongly on the ‘general psychopathology’ factor. Conclusions The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
40. The Psychosis Spectrum in 22q11.2 Deletion Syndrome Is Comparable to That of Nondeleted Youths.
- Author
-
Tang, Sunny X., Moore, Tyler M., Calkins, Monica E., Yi, James J., Savitt, Adam, Kohler, Christian G., Souders, Margaret C., Zackai, Elaine H., McDonald-McGinn, Donna M., Emanuel, Beverly S., Gur, Ruben C., and Gur, Raquel E.
- Subjects
- *
DELETION mutation , *PSYCHOSES , *CHROMOSOME abnormalities , *DISEASES in youths , *STATISTICAL correlation , *PROBABILITY theory , *DIAGNOSIS - Abstract
Background Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and nondeleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity. Methods ND youths ( n = 150) ages 9 to 24 years were matched to 22q11DS individuals ( n = 150) on age and sex, stratifying for presence of psychosis spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes, and for attention-deficit/hyperactivity, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differs from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis. Results Onset of psychosis proneness was similar among 22q11DS (mean: 11.0 years) and ND (mean: 12.1 years) individuals. Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND individuals were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but it did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis spectrum 22q11DS; substance-related disorders were more likely in ND. Global assessment of function was similar in 22q11DS and ND individuals, except among those with low total Structured Interview for Prodromal Syndromes scores. Conclusions Individuals with 22q11DS share overarching similarities with ND individuals in psychosis symptoms and age of onset for psychosis proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
41. Aberrant Cortical Morphometry in the 22q11.2 Deletion Syndrome.
- Author
-
Schmitt, J. Eric, Vandekar, Simon, Yi, James, Calkins, Monica E., Ruparel, Kosha, Roalf, David R., Whinna, Daneen, Souders, Margaret C., Satterwaite, Theodore D., Prabhakaran, Karthik, McDonald-McGinn, Donna M., Zackai, Elaine H., Gur, Ruben C., Emanuel, Beverly S., and Gur, Raquel E.
- Subjects
- *
BRAIN abnormalities , *MAGNETIC resonance imaging of the brain , *THICKNESS measurement , *PEOPLE with schizophrenia ,PSYCHOSES risk factors - Abstract
Background There is increased risk of developing psychosis in 22q11.2 deletion syndrome (22q11DS). Although this condition is associated with morphologic brain abnormalities, simultaneous examination of multiple high-resolution measures of cortical structure has not been performed. Methods Fifty-three patients with 22q11DS, 30 with psychotic symptoms, were compared with demographically matched nondeleted youths: 53 typically developing and 53 with psychotic symptoms. High-resolution magnetic resonance imaging measures of cerebral volume, cortical thickness, surface area, and an index of local gyrification were obtained and compared between groups. Results Patients with 22q11DS demonstrated global increases in cortical thickness associated with reductions in surface area, reduced index of local gyrification, and lower cerebral volumes relative to typically developing controls. Findings were principally in the frontal lobe, superior parietal lobes, and in the paramedian cerebral cortex. Focally decreased thickness was seen in the superior temporal gyrus and posterior cingulate cortex in 22q11DS relative to nondeleted groups. Patterns between nondeleted participants with psychotic symptoms and 22q11DS were similar but with important differences in several regions implicated in schizophrenia. Post hoc analysis suggested that like the 22q11DS group, cortical thickness in nondeleted individuals with psychotic symptoms differed from typically developing controls in the superior frontal gyrus and superior temporal gyrus, regions previously linked to schizophrenia. Conclusions Simultaneous examination of multiple measures of cerebral architecture demonstrates that differences in 22q11DS localize to regions of the frontal, superior parietal, superior temporal, and paramidline cerebral cortex. The overlapping patterns between nondeleted participants with psychotic symptoms and 22q11DS suggest partially shared neuroanatomic substrates. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
42. Subthreshold Psychotic Symptoms in 22q11.2 Deletion Syndrome.
- Author
-
Tang, Sunny X., Yi, James J., Moore, Tyler M., Calkins, Monica E., Kohler, Christian G., Whinna, Daneen A., Souders, Margaret C., Zackai, Elaine H., McDonald-McGinn, Donna M., Emanuel, Beverly S., Bilker, Warren B., Gur, Ruben C., and Gur, Raquel E.
- Subjects
- *
22Q11 deletion syndrome , *CHROMOSOME abnormalities , *SCHIZOPHRENIA , *CAREGIVERS , *YOUTH ,PSYCHOSES risk factors - Abstract
Objective: Chromosome 22q11.2 deletion syndrome (22q11DS) confers 25% risk for psychosis and is an invaluable window for understanding the neurobiological substrate of psychosis risk. The Structured Interview for Prodromal Syndromes (SIPS) is well validated in nondeleted populations for detecting clinical risk but has only recently been applied to 22q11DS. We assessed the largest 22q11DS cohort to date and report on SIPS implementation and symptoms elicited. Method: The SIPS, including its 19 subscales, was administered to 157 individuals with 22q11DS aged 8 to 25 years. Youth and caregiver interviews were conducted and rated separately, then compared for agreement. Implementation of the SIPS in 22q11DS was challenging because of the prevalence of developmental delay and comorbid conditions. However, by explaining questions and eliciting examples, we were able to help youths and caregivers understand and respond appropriately. Consensus ratings were formulated and analyzed with itemwise and factor analysis. Results: Subthreshold symptoms were common, with 85% of individuals endorsing 1 or more. The most commonly rated items were ideational richness (47%) and trouble with focus and attention (44%). Factor analysis revealed a 3-factor solution with positive, negative, and disorganized components. Youth-caregiver comparisons suggested that youths report greater symptoms of perceptual abnormalities, suspiciousness, trouble with emotional expression, and bizarre thinking. Caregivers reported more impaired tolerance to normal stress, poor hygiene, and inattention. Conclusion: The SIPS was adapted for 22q11DS through comprehensive and semi-structured administration methods, yielding a high prevalence of subthreshold psychotic symptoms. The significance and predictive validity of these symptoms require future longitudinal analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
43. 22q11.2 Deletion syndrome and obstructive sleep apnea.
- Author
-
Kennedy, William P., Mudd, Pamela A., Maguire, Meg A., Souders, Margaret C., McDonald-McGinn, Donna M., Marcus, Carole L., Zackai, Elaine H., Solot, Cynthia B., Alexander Mason, Thornton B., Jackson, Oksana A., and Elden, Lisa M.
- Subjects
- *
VELOCARDIOFACIAL syndrome , *SLEEP apnea syndromes , *OPERATIVE otolaryngology , *POLYSOMNOGRAPHY , *VELOPHARYNGEAL insufficiency , *ADENOTONSILLECTOMY , *THERAPEUTICS - Abstract
Otolaryngologic problems are common in the 22q11.2 deletion syndrome (DS) population. Structural anomalies and retrognathia may predispose these patients to obstructive sleep apnea (OSA). The current association of OSA in this population is not defined. Objective (1) Define the frequency of OSA in 22q11.2 DS patients referred for polysomnography (PSG). (2) Determine if OSA is present before and/or after surgery to correct velopharyngeal insufficiency (VPI). (3) Determine effect of prior adenotonsillectomy on OSA following VPI surgery. Methods Retrospective review of children treated from 2006 to 2013 in a tertiary care setting identified by ICD-9 758.32 (velocardiofacial syndrome) and 279.11 (DiGeorge syndrome). Surgical history and PSG data were abstracted from the identified records. Results We identified 323 patients with 22q11.2 DS; 57 (18%) were screened at any point in care using PSG and 15 patients had PSG at multiple time points in care. In most cases, indication for PSG was sleep disordered breathing or pre-operative planning. Overall, 33 patients met criteria for OSA on PSG, accounting for 10.2% of our study population; however, the percentage of patients with OSA was significantly higher within the group of 57 patients (58%) who were screened with PSG. Twenty-one of the screened patients (54%) had PSG prior to any pharyngeal surgery and had mild to severe OSA (obstructive apnea/hypopnea index (AHI): median 5.1/h, range 1.9-25.6). Eighteen patients had PSG after adenotonsillectomy; 8 of these patients (44%) had mild to moderate OSA (median AHI 2.95/h, range 1.9-5.4). Seventeen patients had PSG after VPI surgery (palatopharyngeal flap (PPF) n = 16, sphincteroplasty n = 1). Nine of these patients (53%) had mild to severe OSA (median AHI 3/h, range 1.9-15). Patients who underwent adenotonsillectomy prior to VPI surgery had similar prevalence of OSA (50%, n = 12) than those who did not (OSA: 60%, n = 5, p = 0.70). Most children had mild OSA. Conclusion Prevalence of OSA in this population of 22q11.2 DS patients is higher than expected in the general population. OSA risk is highest after VPI surgery, and may be decreased by adenotonsillectomy. Providers should have awareness of increased prevalence of OSA in patients with 22q11.2 DS. Close monitoring for OSA is warranted given the likelihood of subsequent surgical intervention that can worsen OSA. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
44. A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients
- Author
-
Widdershoven, Josine C.C., Bowser, Mark, Sheridan, Molly B., McDonald-McGinn, Donna M., Zackai, Elaine H., Solot, Cynthia B., Kirschner, Richard E., Beemer, Frits A., Morrow, Bernice E., Devoto, Marcella, and Emanuel, Beverly S.
- Subjects
- *
PHENOTYPES , *GENE expression , *SOFT palate , *DELETION mutation , *HUMAN genetic variation , *SINGLE nucleotide polymorphisms , *NUCLEOTIDE sequence - Abstract
Abstract: Objective: Palatal anomalies are one of the identifying features of 22q11.2 deletion syndrome (22q11.2DS) affecting about one third of patients. To identify genetic variants that increase the risk of cleft or palatal anomalies in 22q11.2DS patients, we performed a candidate gene association study in 101 patients with 22q11.2DS genotyped with the Affymetrix genome-wide human SNP array 6.0. Methods: Patients from Children''s Hospital of Philadelphia, USA and Wilhelmina Children''s Hospital Utrecht, The Netherlands were stratified based on palatal phenotype (overt cleft, submucosal cleft, bifid uvula). SNPs in 21 candidate genes for cleft palate were analyzed for genotype–phenotype association. In addition, TBX1 sequencing was carried out. Quality control and association analyses were conducted using the software package PLINK. Results: Genotype and phenotype data of 101 unrelated patients (63 non-cleft subjects (62.4%), 38 cleft subjects (37.6%)) were analyzed. A Total of 39 SNPs on 10 genes demonstrated a p-value ≤0.05 prior to correction. The most significant SNPs were found on FGF10. However none of the SNPs remained significant after correcting for multiple testing. Conclusions: Although these results are promising, analysis of additional samples will be required to confirm that variants in these regions influence risk for cleft palate or palatal anomalies in 22q11.2DS patients. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
45. Affective disorders and other psychiatric diagnoses in children and adolescents with 22q11.2 Deletion Syndrome
- Author
-
Jolin, Edith M., Weller, Ronald A., Jessani, Naushad R., Zackai, Elaine H., McDonald-McGinn, Donna M., and Weller, Elizabeth B.
- Subjects
- *
AFFECTIVE disorders , *PSYCHIATRIC diagnosis , *CHROMOSOME abnormalities , *PATHOLOGICAL psychology , *BIPOLAR disorder , *SCHIZOPHRENIA , *ADULTS , *CHILD psychiatry - Abstract
Abstract: Background: 22q11.2 Deletion Syndrome (22qDS) is a common chromosome deletion syndrome that has been associated with severe psychopathology, including bipolar disorder and schizophrenia, in adults. Assessment of psychiatric diagnoses in children and adolescents with 22qDS is in the early stages of investigation. Methods: 24 children and adolescents with 22qDS established by chromosomal analysis were randomly selected from a 22qDS clinic. Children and their parents were interviewed by trained psychometricians with a standardized structured diagnostic interview. A diagnosis was considered present if DSM-IV diagnostic criteria were met on either the parent or the child interview. Results: 24 22qDS subjects (mean age 9.7±3.3 years) had a mean of two DSM-IV psychiatric disorders. 79% met criteria for at least one DSM-IV psychiatric disorder and over one third had three or more diagnoses. 12.5% met criteria for major depression but none had bipolar disorder. Anxiety disorders (54%), attention-deficit/hyperactivity disorder (38%), and oppositional defiant disorder (38%) were common. Although 29% reported at least one psychotic-like symptom, none met criteria for a psychotic disorder. Limitations: Small sample size may have obscured significant associations. Other limitations included non-blinded interviewers and lack of a simultaneously studied control group. Conclusion: Affective, anxiety, attentional, and behavioral disorders were relatively common in this randomly selected group of children and adolescents with 22qDS. No child met criteria for bipolar disorder or schizophrenia. Prospective, longitudinal study is needed to determine whether early psychiatric symptomatology in children with 22qDS predicts continuing or more severe psychopathology later in life. Early psychiatric screening and monitoring appears warranted in 22qDS patients. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
46. A 3.1-Mb microdeletion of 3p21.31 associated with cortical blindness, cleft lip, CNS abnormalities, and developmental delay
- Author
-
Haldeman-Englert, Chad R., Gai, Xiaowu, Perin, Juan Carlos, Ciano, Melissa, Halbach, Sara S., Geiger, Elizabeth A., McDonald-McGinn, Donna M., Hakonarson, Hakon, Zackai, Elaine H., and Shaikh, Tamim H.
- Subjects
- *
CENTRAL nervous system abnormalities , *DEVELOPMENTAL delay , *VISION disorders , *CLEFT lip , *DISEASES in women , *NEURONS , *DNA microarrays - Abstract
Abstract: We report a 3.1-Mb de novo deletion of 3p21.31 in a 3.5-year-old female with cortical blindness, cleft lip, CNS abnormalities, and gross developmental delays. Examination of the region showed ∼80 genes to be involved in the deletion. Functional analysis of the deleted genes suggests that several of them may be important in normal neuronal maturation and function. Thus, haploinsufficiency of one or more of these genes could potentially contribute to the observed phenotype. Our patient does not have clinical features that overlap completely with either proximal or distal 3p deletions, suggesting that the deletion seen in our patient leads to a distinct clinical phenotype not described previously. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
47. Corpus callosum morphology and ventricular size in chromosome 22q11.2 deletion syndrome
- Author
-
Machado, Alexei M.C., Simon, Tony J., Nguyen, Vy, McDonald-McGinn, Donna M., Zackai, Elaine H., and Gee, James C.
- Subjects
- *
HUMAN chromosome abnormalities , *CORPUS callosum , *COGNITIVE ability , *COGNITION , *CHROMOSOME abnormalities - Abstract
Abstract: In this paper, novel methods were used to map the corpus callosum morphology of children with chromosome 22q11.2 deletion syndrome in order to further investigate changes to that structure and to examine their possible effects on cognitive function. The callosal profiles were extracted from the centermost MRI midsagittal slice by supervised thresholding and the structure''s boundary and midline were computed automatically. Difference analysis was based on non-rigid registration, in which a template image is warped to conform to the shape of each corpus callosum in the sample. Boundaries and midlines were registered to a template and the results used to determine the average callosal shapes for children with the deletion and for controls. Pointwise registration also enabled the detailed evaluation of callosal curvature, width, area and length. Significant differences between the two groups were found in shape, size and bending angle. Results showed group differences that were concentrated in the anterior part of the structure, more specifically in the rostrum, which was larger and longer in the group with the syndrome. Correlation analyses showed that ventricular enlargement does not fully account for callosal morphology differences in children with the deletion. However, areal measurements did reveal important relationships between changes in callosal morphology and cognitive function. These novel findings reveal intricate relationships between genetic and disease-specific factors in the callosal anatomy and the potential impact of those changes on cognitive functions. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
48. Specific cerebellar reductions in children with chromosome 22q11.2 deletion syndrome
- Author
-
Bish, Joel P., Pendyal, Akshay, Ding, Lijun, Ferrante, Heather, Nguyen, Vy, McDonald-McGinn, Donna, Zackai, Elaine, and Simon, Tony J.
- Subjects
- *
PATHOLOGICAL psychology , *CEREBELLUM diseases , *MENTAL health , *BRAIN diseases - Abstract
Abstract: Children with chromosome 22q11.2 deletion syndrome commonly are found to have morphological brain changes, cognitive impairments, and elevated rates of psychopathology. One of the most commonly and consistently reported brain changes is reduced cerebellar volume. Here, we demonstrate that, in addition to the global cerebellum reductions previously reported, volumetric reductions of the anterior lobule and the vermal region of the neo-cerebellum in the mid-sagittal plane best differentiate children with the deletion from typically developing children. These results suggest that the morphological changes of specific portions of the cerebellum may be an important underlying substrate of cognitive impairments and increased incidence of psychopathology in this group. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
49. Cardiac Magnetic Resonance Imaging for Accurate Diagnosis of Aortic Arch Anomalies in Patients with 22q11.2 Deletion
- Author
-
Johnson, Tiffanie R., Goldmuntz, Elizabeth, McDonald-McGinn, Donna M., Zackai, Elaine H., and Fogel, Mark A.
- Subjects
- *
CARDIAC magnetic resonance imaging , *DIAGNOSTIC imaging , *ECHOCARDIOGRAPHY , *HEART anatomy - Abstract
This study demonstrates, in patients with 22q11.2 deletion, the wide variety of complex aortic arch anomalies that can be accurately defined by cardiac magnetic resonance imaging (MRI) compared with echocardiography. From May 1999 to August 2003, 17 of 68 patients (25%) with 22q11.2 deletion referred for cardiac evaluation required cardiac MRI, after echocardiography, to clarify aortic arch anatomy. Images of cardiac anatomy were obtained using steady-state free precession, half-Fourier acquired single turbo spin-echo dark blood sequences and gadolinium for 3-dimensional reconstruction. All MRI findings were abnormal, and in 16 of 17 cases, echocardiography was unable to define aortic arch anomalies correctly compared with MRI. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
50. Chromosomal and cardiovascular anomalies associated with congenital laryngeal web
- Author
-
McElhinney, Doff B., Jacobs, Ian, McDonald-McGinn, Donna M., Zackai, Elaine H., and Goldmuntz, Elizabeth
- Subjects
- *
LARYNGEAL diseases , *CYTOGENETICS - Abstract
Objective: The purpose of this study was to estimate the frequency of chromosomal and cardiovascular anomalies associated with a congenital laryngeal web. Methods: We reviewed our experience with 25 patients who underwent intervention for a symptomatic congenital laryngeal web between 1988 and 2000, in order to investigate the frequency of associated chromosomal and cardiovascular anomalies. Twelve patients underwent cytogenetic evaluation, including seven that were tested for a chromosome 22q11 deletion by fluorescence in situ hybridization. Results: Chromosomal abnormalities were detected in seven of the 12 patients in whom cytogenetic evaluation was performed (28% of the entire cohort), including a chromosome 22q11 deletion in six and trisomy 21 in one. Associated cardiovascular anomalies were diagnosed in nine of the 25 patients, most commonly aortic arch anomalies. Of the patients with cardiovascular anomalies, 55% also had chromosomal alterations, and 71% of patients with chromosomal alterations also had a cardiovascular defect, of which four had the triad of a congenital laryngeal web, a chromosome 22q11 deletion, and congenital cardiovascular anomalies. Conclusions: Chromosomal and cardiovascular anomalies are common in patients with a congenital laryngeal web. A chromosome 22q11 deletion was particularly common, as were the cardiovascular anomalies associated with the chromosome 22q11 deletion syndrome. Accordingly, patients with a congenital laryngeal web should undergo genetic screening, including evaluation for a chromosome 22q11 deletion, and a thorough cardiovascular evaluation, including imaging of the aortic arch. Particular attention should be paid to identifying patients with the triad of a congenital laryngeal web, a chromosome 22q11 deletion, and cardiovascular anomalies, particularly a vascular ring. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.