Medicine and Health Sciences Commons^™

Velo-Cardio-Facial Syndrome: 30 Years Of Study, Robert Shprintzen

Robert J. Shprintzen

Velo-cardio-facial syndrome is one of the names that has been attached to one of the most common multiple anomaly syndromes in humans. The labels DiGeorge sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22, and Sedlačková syndrome have all been attached to the same disorder. Velo-cardio-facial syndrome has an expansive phenotype with more than 180 clinical features described that involve essentially every organ and system. The syndrome has drawn considerable attention because a number of common psychiatric illnesses are phenotypic features including attention deficit disorder, schizophrenia, and bipolar disorder. The expression is highly variable with some individuals being essentially …

Overt Cleft Palate Phenotype And Tbx1 Genotype Correlations In Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients, Sean Herman, Tingwei Guo, Donna Mcdonald Mcginn, Anna Blonska, Alan Shanske, Anne Bassett, Eva Chow, Mark Bowser, Molly Sheridan, Frits Beemer, Koen Devriendt, Ann Swillen, Jeroen Breckpot, Maria Digilio, Bruno Marino, Bruno Dallapiccola, Courtney Carpenter, Xin Zheng, Jacob Johnson, Jonathan Chung, Anne Marie Higgins, Nicole Philip, Tony Simon, Karlene Coleman, Damian Heine Suñer, Jordi Rosell, Wendy Kates, Marcella Devoto, Elaine Zackai, Tao Wang, Robert Shprintzen, Beverly Emanuel, Bernice Morrow, International Chromosome 22q11.2 Consortium

Robert J. Shprintzen

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000 – 1/4,000 live births. Approximately 9–11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, …

Catatonia In An Adolescent With Velo-Cardio-Facial Syndrome, Gianni Faedda, Lee Wachtel, Anne Marie Higgins, Robert Shprintzen

Robert J. Shprintzen

Velo-cardio-facial syndrome (VCFS) is the most common microdeletion syndrome in humans and is probably the most frequent genetic cause of psychosis currently known. Many psychiatric disorders have been reported to occur in people with VCFS including, but not limited to schizophrenia, unipolar and bipolar mood disorders (with or without psychotic features), schizoaffective disorder, psychosis NOS, social phobia, generalized and separation anxiety, obsessive-compulsive disorder, autism spectrum disorder, cognitive impairment, and ADHD. This report describes the psychiatric onset and development of catatonia in an adolescent female with VCFS that was undiagnosed until 15 years of age. Catatonia may be a relatively common …

Pharyngeal Flap And Obstructive Apnea: Maximizing Speech Outcome While Limiting Complications, Burke Chegar, Robert Shprintzen, Michael Curtis, Sherard Tatum

Robert J. Shprintzen

Objective To assess speech results and rate of obstructive sleep apnea using a modified, superiorly based pharyngeal flap performed after staged adenotonsillectomy in a group with velopharyngeal insufficiency. Methods In this nonrandomized, retrospective case series (July 1, 1996, through June 30, 2003), patients were mainly children referred to a multispecialty craniofacial clinic. Patients underwent staged adenotonsillectomy 2 months before width-customized pharyngeal flap surgery. Short flaps were created high above the level of the palate, just long enough to reach the nasal surface. Donor sites were closed by superior advancement of the inferior posterior pharyngeal wall tissue. Cardiopulmonary and oximetry data …

Cervical Vascular And Upper Airway Asymmetry In Velo-Cardio-Facial Syndrome: Correlation Of Nasopharyngoscopy With Mra, Avi Oppenheimer, Susan Fulmer, Keivan Shifteh, Ja-Kwei Chang, Allan Brook, Alan Shanske, Robert Shprintzen

Robert J. Shprintzen

Purpose Velo-cardio-facial syndrome (VCFS), the most common genetic syndrome causing cleft palate, is associated with internal carotid and vertebral artery anomalies, as well as upper airway asymmetry. Medially displaced internal carotid arteries, often immediately submucosal, present a risk of vascular injury during pharyngeal flap surgery for velopharyngeal insufficiency (VPI). We evaluate the frequency and spectrum of cervical vascular anomalies in a large cohort of VCFS patients correlating MRA with nasopharyngolaryngoscopy in detecting at risk carotid arteries. Furthermore, we assess the relationship with respect to laterality between cervical vascular patterns and the asymmetric abnormalities of these subjects’ upper airways. Methods Cervical …

The Effects Of Gender And Catechol O-Methyltransferase (Comt) Val108/158met Polymorphism On Emotion Regulation In Velo-Cardio-Facial Syndrome (22q11.2 Deletion Syndrome): An Fmri Study, Ioana Coman, Matthew Gnirke, Frank Middleton, Kevin Antshel, Wanda Fremont, Anne Higgins, Robert Shprintzen, Wendy Kates

Robert J. Shprintzen

Velo-cardio-facial syndrome (VCFS) is caused by a micro-deletion of over 40 genes at the q11.2 locus of chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. COMT, one of the genes located in the deleted region, has been considered as a major candidate gene for genetic susceptibility in psychiatric diseases. Its functional polymorphism Val108/158Met has been shown to affect prefrontal function and working memory and has been associated with emotional dysregulation. We utilized a functional magnetic resonance imaging (fMRI) event-related paradigm to asses COMT genotype and gender-moderated effects on the neural activation that …

Comparing Phenotypes In Patients With Idiopathic Autism To Patients With Velocardiofacial Syndrome (22q11 Ds) With And Without Autism, Wendy Kates, Kevin Antshel, Wanda Fremont, Robert Shprintzen, Leslie Strunge, Courtney Burnette, Anne Marie Higgins

Robert J. Shprintzen

At least three research groups have reported that autism is diagnosed in up to 20% of children with velocardiofacial syndrome (VCFS). However the degree of phenotypic overlap between VCFS-affected children with autism and those with idiopathic autism has not been established. The purpose of this study was to define and differentiate the behavioral phenotype of autism in samples of children with either (VCFS) or idiopathic autism. Five groups of children ages 5–15 were included in the between-group design. Parent report of autism behaviors (based on the Autism Diagnostic Interview-Revised, ADI-R) were compared between children with VCFS, children with VCFS and …

Associations Between Performance On The Rey-Osterrieth Complex Figure And Regional Brain Volumes In Children With And Without Velocardiofacial Syndrome, Kevin Antshel, Jena Peebles, Nuria Abdulsabur, Anne Marie Higgins, Nancy Roizen, Robert Shprintzen, Wanda Fremont, Robert Natasi, Wendy Kates

Robert J. Shprintzen

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white …

Cortical Gyrification In Velo-Cardio-Facial (22q11.2 Deletion) Syndrome: A Longitudinal Study, Arun Kunwar, Seethalakshmi Ramanathan, Joshua Nelson, Kevin Antshel, Wanda Fremont, Anne Higgins, Robert Shprintzen, Wendy Kates

Robert J. Shprintzen

Introduction: Velo-cardio-facial syndrome (VCFS) has been identified as an important risk factor for psychoses, with up to 32% of individuals with VCFS developing a psychotic illness. Individuals with VCFS thus form a unique group to identify and explore early symptoms and biological correlates of psychosis. In this study, we examined if cortical gyrification pattern, i.e. gyrification index (GI) can be a potential neurobiological marker for psychosis. Method: GIs of 91 individuals with VCFS were compared with 29 siblings and 54 controls. Further, 58 participants with VCFS, 21 siblings and 18 normal controls were followed up after 3 years and longitudinal …

Adhd, Major Depressive Disorder, And Simple Phobias Are Prevalent Psychiatric Conditions In Youth With Velocardiofacial Syndrome, Kevin Antshel, Wanda Fremont, Nancy Roizen, Robert Shprintzen, Anne Marie Higgins, Amit Dhamoon, Wendy Kates

Robert J. Shprintzen

Objective: To examine prevalence rates of psychopathology in children with velocardiofacial syndrome (VCFS).

Method: One hundred fifty-four children ages 6 to 15 participated in our between-group design with three samples, 84 children with VCFS (37 girls, 47 boys), 32 sibling controls (18 girls, 14 boys), and 38 community controls (12 girls, 26 boys). The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and several other parent report measures were used to assess for psychopathology.

Results: Compared to both control samples, children with VCFS had higher prevalence rates of major depressive disorder, attention-deficit/hyperactivity disorder, simple phobias, and …

Temperament In Velocardiofacial Syndrome, Kevin Antshel, K. Stallone, Nuria Abdulsabur, Robert Shprintzen, Nancy Roizen, Anne Marie Higgins, Wendy Kates

Robert J. Shprintzen

Background Velocardiofacial syndrome (VCFS) is a microdeletion syndrome caused by a 22q11.2 chromosomal deletion. Methods In this study, parents reported on their own temperament as well as the temperament of their child. Sixty-seven children with VCFS (mean age = 10.8, SD = 2.8; range 6–15), and age-, race- and gender-ratio matched samples of 47 community control participants (mean age = 10.4, SD = 2.6; range 6–15), and 18 sibling control participants (mean age = 12.1, SD = 1.9; range 9–15) took part in the current project. Results Children with VCFS have a temperament that may best be described as modestly …

Velopharyngeal Insufficiency: Diagnosis And Management, Robert Shprintzen, Eileen Marrinan

Robert J. Shprintzen

Journal articles relevant to the diagnosis and treatment of velopharyngeal insufficiency were reviewed. All studies ascertained by PubMed search were included. Recent findings: Studies reported on the application of magnetic resonance scanning, reliability tests of the International Working Group diagnostic protocol, the use of nasometry, and techniques designed to assess the function of the velopharyngeal mechanism. Treatment studies focused on outcomes in small samples of cases and complication rates from pharyngeal flap. One study discussed ineffective speech therapy procedures. Summary: There were relatively few studies this past year. Those that were published were hindered by small and heterogeneous sample sizes …

Cognitive And Psychiatric Predictors To Psychosis In Velocardiofacial Syndrome: A 3-Year Follow-Up Study, Kevin Antshel, Robert Shprintzen, Wanda Fremont, Anne Higgins, Stephen Faraone, Wendy Kates

Robert J. Shprintzen

Objective: To predict prodromal psychosis in adolescents with velocardiofacial syndrome (VCFS). Method: 70 youth with VCFS, 27 siblings of youth with VCFS and 25 community controls were followed from childhood (Mean age = 11.8 years) into mid-adolescence (mean age 15.0 years). Psychological tests measuring intelligence, academic achievement, learning/memory, attention and executive functioning as well as measures of parent and clinician ratings of child psychiatric functioning were completed at both time point. Results: Major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder diagnoses increased in the VCFS sample. With very low false positive rates, the best predictor of adolescent prodromal …

The Macarthur Adjudicative Competence Study: The Development And Validation Of A Research Instrument, Steven Hoge, Richard Bonnie, Norman Poythress, John Monahan

Norman Poythress

Assessment of competence to stand trial is a common evaluation that can have substantial consequences for defendants and the criminal justice system. Despite a voluminous literature, much remains unknown. An obstacle to progress in understanding what is better termed ldquoadjudicative competencerdquo is the absence of structured, standardized research measures for assessment of defendants. This article presents the legal framework, assessment strategy, instrument description, psychometric properties, and construct validation of the MacArthur Structured Assessment of the Competencies of Criminal Defendants (MacSAC-CD). The measures meet or exceed accepted indices of internal consistency, and interscorer agreement. Observed patterns of correlations among measures support …

Displacement Across A Fracture Gap With Axial Loading Of Far Cortical Locking Constructs, Peter Wagner, Dennis Murphy, Kristen Billiar, Judith Siegel, John Wixted

Kristen L. Billiar

Purpose: Far cortical locking has been proposed for reducing stiffness and promoting greater dynamic stability in locked plating constructs. Prior studies have shown reduced stiffness with axial loading of these constructs, leading to a theoretical increase in inter-fragmentary motion and secondary bone healing. The purpose of this study was to examine strain across a fracture gap using far cortical locking constructs in a biomechanical model of distal femoral fractures.

Methods: Fourth generation sawbones were cut transversely along the distal diaphysis and plated with distal femoral buttress plates and cortical locking screws. Far cortical locking (FCL) specimens were predrilled in the …

Explaining The Longitudinal Association Between Puberty And Depression: Sex Differences In The Mediating Effects Of Peer Stress, Colleen Conley, Karen Rudolph, Fred Bryant

Colleen S. Conley

This research investigated whether exposure to peer stress serves as one pathway through which pubertal development contributes to depression over time, differentially for girls and boys. Youth (N = 149; 9.6–14.8 years) and their caregivers provided information at two waves, 1 year apart, on puberty (Wave 1), peer stress (occurring between Waves 1 and 2), and depression (Waves 1 and 2). Structural equation modeling analyses examined sex differences in the extent to which peer stress mediated the impact of pubertal status and timing on subsequent depression (i.e., tests of moderated mediation). Significant sex-moderated mediation was found for both pubertal status …

Correspondence Between Self-Report And Interview-Based Assessments Of Antisocial Personality Disorder, Laura Guy, Norman Poythress, Kevin Douglas, Jennifer Skeem

Norman Poythress

Antisocial personality disorder (ASPD) is associated with suicide, violence, and risk-taking behavior and can slow response to first-line treatment for Axis I disorders. ASPD may be assessed infrequently because few efficient diagnostic tools are available. This study evaluated 2 promising self-report measures for assessing ASPD—the ASPD scale of the Personality Diagnostic Questionnaire-4 (PDQ-4; S. E. Hyler, 1994) and the Personality Assessment Inventory (PAI; L. Morey, 1991, 2007)—as well as the ASPD module of the Structured Clinical Interview for DSM–IV Axis II (SCID-II; M. B. First, R. L. Spitzer, M. Gibbon, J. B. W. Williams, & L. S. Benjamin, 1997). The …

An Improved Murine Femur Fracture Device For Bone Healing Studies, Joseph Marturano, Benjamin Cleveland, Melissa Bryne, Shannon O'Connell, John Wixted, Kristen Billiar

Kristen L. Billiar

Murine models are commonly used to investigate bone healing and test new treatments before human trials. Our objective was to design an improved murine femur fracture device and determine optimal mass and velocity settings for maximal likelihood of transverse fracture. Fracture reproducibility was maximized using an adjustable kinetic energy level, a novel mouse positioning system and an electromagnet striker release assembly. Sixty wild-type mice of 8-12-week-old male and female with a weight of 26.4+/-6.1g were subjected to an experimental postmortem fracture in the left and right femur (n=120) using variable kinetic energy inputs. A best-fit prediction equation for transverse fracture …

The Effects Of Home-Based Pilates In Healthy College-Age Females, Betsy Donahoe-Fillmore, Mary Fisher, C. Brahler

C. Jayne Brahler

Objectives: To quantify and determine the effects of Pilates on core endurance, hamstring flexibility, balance, body composition/mass and perceived stress level in healthy college age females.

Study Design: Randomized controlled trial design.

Background: Emerging research on the Pilates technique is inconclusive regarding benefits to core endurance, flexibility, balance, body mass, and perceived stress.

Methods and Measures: Female college students (n=57; 18-35 years old) were randomly assigned to a Pilates group, who exercised at home with a DVD, or a control group who did not engage in Pilates practice. Core endurance, hamstring flexibility, balance, body composition and stress measurements were taken …

A Comparison Of Two Pelvic Floor Muscle Training Programs In Females With Stress Urinary Incontinence: A Pilot Study, Betsy Donahoe-Fillmore, Wendy Chorny, C. Brahler, Ashley Ingley, Jennifer Kennedy, Valerie Osterfeld

C. Jayne Brahler

Background: Stress urinary incontinence (SUI) is a condition affecting millions of Americans. Few studies have assessed the benefits of different exercises involved in pelvic floor muscle training (PFMT). Purposte: The purpose of this study was to compare the effects of a traditional PFMT program to an assisted pelvic floor muscle training (APFMT) program that included contraction of hip musculature.

Mentally Ill And Non-Mentally Ill Defendants' Abilities To Understand Information Relevant To Adjudication: A Preliminary Study, Steven Hoge, Norman Poythress, Richard Bonnie, Marlene Eisenberg

Norman Poythress

The legal construct of competence to stand trial, or “adjudicative competence,” is based on the premise that some mentally disordered defendants have impaired abilities when compared with most defendants and that adjudication should be barred if these competence-related abilities are significantly impaired. Where the line is drawn between sufficient and insufficient abilities has important consequences: as a result of being adjudicated incompetent, defendants may be detained and treated involuntarily and their trials will be delayed. However, no studies have systematically compared the capacities of relevant groups of defendants. In this studv. 84 criminal defendants—42 of whom were hospitalized as incompetent …

Measurement Invariance Of The Kidney Disease And Quality Of Life Instrument (Kdqol-Sf) Across Veterans And Non-Veterans, Karen Saban, Fred Bryant, Dominic Reda, Kevin Stroupe, Denise Hynes

Fred B. Bryant

Background Studies have demonstrated that perceived health-related quality of life (HRQOL) of patients receiving hemodialysis is significantly impaired. Since HRQOL outcome data are often used to compare groups to determine health care effectiveness it is imperative that measures of HRQOL are valid. However, valid HRQOL comparisons between groups can only be made if instrument invariance is demonstrated. The Kidney Disease Quality of Life-Short Form (KDQOL-SF) is a widely used HRQOL measure for patients with chronic kidney disease (CKD) however, it has not been validated in the Veteran population. Therefore, the purpose of this study was to examine the measurement invariance …

Abortion/Reproductive Rights, Sandra Klein

Sandra S. Klein

The issue of a woman's right to choose whether or not to continue with a pregnancy has proven to be complicated for many reasons, not the least of which is the implications for a person's right to do with her body as she sees fit. The bibliography that follows provides the researcher with an in depth look at this issue, with an emphasis on the privacy aspects.

Externalizing Disorders Of Childhood And Adolescence, P.J. Frick, Eva Kimonis

Eva Kimonis

No abstract provided.

Test Items In The Complete And Short Forms Of The Bot-2 That Contribute Substantially To Motor Performance Assessments In Typically Developing Children 6-10 Years Of Age, Kadi Carmosino, Ashley Grzeszczak, Kaylie Mcmurray, Ali Olivo, Bo Slutz, Brittany Zoll, Betsy Donahoe-Fillmore, C. Brahler

C. Jayne Brahler

Objectives: Determine the magnitude of association between individual subtest items of the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), and the respective total subtest scores and to review items on the BOT-2 Short Form. Background: The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), is a test used to measure gross motor proficiency in both typically developing children and children with developmental disabilities between the ages of four and twenty-one. The BOT-2 Short Form consists of fourteen test items proportionally selected from the subtests of the Complete Form. It can be used as a screening tool and takes less …

Explaining The Longitudinal Association Between Puberty And Depression: Sex Differences In The Mediating Effects Of Peer Stress, Colleen Conley, Karen Rudolph, Fred Bryant

Fred B. Bryant

This research investigated whether exposure to peer stress serves as one pathway through which pubertal development contributes to depression over time, differentially for girls and boys. Youth (N = 149; 9.6–14.8 years) and their caregivers provided information at two waves, 1 year apart, on puberty (Wave 1), peer stress (occurring between Waves 1 and 2), and depression (Waves 1 and 2). Structural equation modeling analyses examined sex differences in the extent to which peer stress mediated the impact of pubertal status and timing on subsequent depression (i.e., tests of moderated mediation). Significant sex-moderated mediation was found for both pubertal status …

The Broward Mental Health Court: Process, Outcomes, And Service Utilization, Roger Boothroyd, Norman Poythress, Annette Christy, John Petrila

Norman Poythress

Mental health courts are one of a variety of special jurisdiction courts that have been created in a number of countries, including the United States (Petrila, 2003). While there is no prototypical mental health court (Steadman, Davidson, & Brown, 2001; Watson, Luchins, & Hanrahan, 2001), most of those in existence today share several common characteristics. These include (a) the creation of a special docket (usually, but not always, nonviolent misdemeanants with mental illness) that is (b) handled by a particular judge, with (c) a primary goal of diverting defendants from the criminal justice system and into treatment (Goldkamp & Irons-Guynn, …

Psychopathic Features In A Juvenile Diversion Population: Reliability And Predictive Validity Of Two Self-Report Measures, Diana Falkenbach, Norman Poythress, Kathleen Heide

Norman Poythress

The reliability and predictive validity of two experimental self-report versions of two measures of psychopathic features in youth, the Antisocial Process Screening Device (APSD: Frick & Hare, 2001) and a modified version of the Child Psychopathy Scale (CPS: Lynam, 1997) were examined in a sample of 69 arrested youth (M age¼14.4 years) referred to a juvenile diversion program. Parents or legal guardians completed parent-rating versions of the same measures. Reliability indicators for the APSD total measure were satisfactory although internal consistency indices (coefficient alpha) for the Callous/Unemotional and Impulsive/Conduct Problems scales were slightly lower than desirable. Reliability indicators for the …

Evaluation Of The Hare-Pscan In A Non-Clinical Population, Cristal Elwood, Norman Poythress, Kevin Douglas

Norman Poythress

Using 100 university undergraduates as participants, this study examined the structural reliability and construct validity of Hare and Hervé's P-SCAN (Hare & Hervé, 1999) a 90-item measure that purports to serve as an “… early warning system” or “rough screening device” (p. 1) for identifying individuals with substantial psychopathic features. Internal consistency indices (e.g. Cronbach's α, mean inter-item correlations) for the three P-SCAN subscales (Interpersonal, Affective, Lifestyle) suggested excellent reliability. Statistically significant, though modest correlations (range 0.21–0.33) were obtained in 5 of 6 comparisons with the self-report Primary psychopathy and Secondary psychopathy scales developed by Levenson, Kiehl, and Fitzpatrick (1995) …

An Analysis Of Functional Status In Multiple Sclerosis Patients After Progressive Non-Aerobic High-Intensity Maximal Effort Exercise (Mee), Hilda Lai, Michael Kuchera, R Dombroski, T Vardy, F Thomas, S O’Brien, P Yagnik, K Wenzel, S Stoll, Bruce Stouch, M. T. Wallin, I. Vargas,, Olufolake Odutola

Michael Kuchera

Background: Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. MS patient function has been assessed using Multiple Sclerosis Functional Composite Score (MSFCS). The MSFCS includes the standardized scores (Z-score) of three functional tests: the Paced Auditory Serial Addition Test (PASAT-3”) for cognitive function, 9-Hole Peg Test (9-HPT) for upper extremity function, and timed 25-foot walk (25-TW) for lower extremity function. One of the most common symptoms experienced by MS patients is severe fatigue, often brought on suddenly by aerobic exercise. Non-aerobic maximal effort exercise (MEE) is thought to increase strength without increasing fatigue. The IsoPUMP® …