Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

The Diagnosis Of Severe Combined Immunodeficiency: Implementation Of The Pidtc 2022 Definitions, Christopher C. Dvorak, Elie Haddad, Jennifer Heimall, Elizabeth Dunn, Morton J. Cowan, Sung-Yun Pai, Neena Kapoor, Lisa Forbes Satter, Rebecca H. Buckley, Richard J. O'Reilly, Sharat Chandra, Jeffrey J. Bednarski, Olatundun Williams, Ahmad Rayes, Theodore B. Moore, Christen L. Ebens, Blachy J. Davila Saldana, Aleksandra Petrovic, Deepak Chellapandian, Geoffrey D. E. Cuvelier, Mark T. Vander Lugt, Emi H. Caywood, Shanmuganathan Chandrakasan, Hesham Eissa, Frederick D. Goldman, Evan Shereck, Victor M. Aquino, Kenneth B. Desantes, Lolie Yu, Et Al

School of Medicine Faculty Publications

Background: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID. Objective: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. Methods: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. Results: According to PIDTC 2022 Definitions, 18 of 353 …

Should Health Systems Share Genetic Findings With At-Risk Relatives When The Proband Is Deceased? Interviews With Individuals Diagnosed With Lynch Syndrome, Jessica Ezzell Hunter, Jennifer L. Schneider, Alison J. Firemark, James V. Davis, Sara Gille, Pamala A. Pawloski, Su-Ying Liang, Victoria Schlieder, Alanna Kulchak Rahm

Journal of Patient-Centered Research and Reviews

Purpose: Genetic information has health implications for patients and their biological relatives. Death of a patient before sharing a genetic diagnosis with at-risk relatives is a missed opportunity to provide important information that could guide interventions to minimize cancer-related morbidity and mortality in relatives.

Methods: We performed semi-structured interviews with individuals diagnosed with Lynch syndrome at 1 of 4 health systems to explore their perspectives on whether health systems should share genetic risk information with relatives following a patient’s death. An inductive, open-coding approach was used to analyze audio-recorded content, with software-generated code reports undergoing iterative comparative analysis by a …

Comprehensive Care To Improve Quality Of Life: A Case Of Childhood Adrenoleukodystrophy, Miraal S. Dharamsi, Adrian A. Mejia, Cecilia De Vargas

HCA Healthcare Journal of Medicine

The childhood cerebral form of adrenoleukodystrophy (ALD) causes rapid demyelination of cerebral white matter and is clinically characterized by hyperactivity, emotional changes, and poor school performance, as well as progressive cognitive, visual, auditory, speech, and motor decline. While aggressive behavior is a known complication of ALD, treatment of the disease is limited. Moreover, behavioral management is not well described in the available literature, particularly from a psychiatric standpoint. In this case presentation, the patient’s parents reported significant agitation and aggression, which may have been secondary to verbal deficits, in addition to the general neuropathological implications of this disease. Although this …

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …

The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle

Theses and Dissertations (ETD)

CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …

Sociodemographic And Biological Factors Of Health Disparities Of Mothers And Their Very Low Birth-Weight Infants, June Cho, Lung-Chang Chien, Diane Holdtich-Davis

Nursing Faculty Research

Background: Black mothers and their very low birth-weight infants in the United States have increased risk of adverse neonatal and maternal health outcomes compared with White mothers and infants. Disparities in adverse birth outcomes associated with sociodemographic factors are difficult to quantify and modify, limiting their usefulness in assessing intervention effects. Purpose: To test hypotheses that (1) the biological factors of maternal testosterone and cortisol are associated with sociodemographic factors and (2) both factors are associated with neonatal health and maternal mental health and healthy behaviors between birth and 40 weeks' gestational age. Methods: We used a descriptive, longitudinal design. …

Case Report: How A Vallecular Cyst Could Have Become An Airway Emergency, Adam Kandil, Robin Lahr, Andrew Caravello

Rowan-Virtua Research Day

Vallecular cysts, also known as epiglottic mucous retention cysts are known to be generally self-limiting laryngeal lesion. They can however also be associated with airway obstruction, and dysphagia in infants. In adults, they are usually asymptomatic, and usually incidentally diagnosed. At times they are diagnosed during rapid sequence intubation, as they may contribute to endotracheal intubation difficulty. Moreover, there is question as to the correlation between vallecular cysts and the incidence of acute epiglottitis, as a vallecular cyst may become infected and cause a localized expansion of inflammation and infection. This expansion from the vallecula progresses to epiglottis.

Paradoxical Dat In A Term Newborn With Physiological Jaundice, Abiram Sivanandam, Tomas Rotschild

Rowan-Virtua Research Day

The Direct Antigen Test (DAT) is used to find out if a newborn has maternally-produced antibodies against the newborn’s red blood cells. We discuss the case of a term newborn male with an O+ blood type born to a mother whose blood type is A+. As a part of routine screening, DAT of umbilical cord blood was obtained, which resulted positive. While the neonate had jaundice, the overall clinical picture pointed more toward neonatal physiological jaundice rather than a potential hemolytic anemia expected with a positive DAT. This discrepancy prompted us to review literature to explain our findings.

A Hidden Cause For Electrolyte Derangement In The Ed: Gitelman Syndrome, Alexis Dunn, James Espinosa, Alan Lucerna, Kevin Dwyer

Rowan-Virtua Research Day

Electrolyte derangements are a common finding in the emergency department, whether incidental or the cause for presenting symptoms. Gitelman syndrome (GS) can be the cause for recurrent hypokalemia and hypomagnesemia. While often diagnosed when the patient is young, a clinician should keep this on the differential when seeing repeated visits with electrolyte deficiencies and treating them. Here we discuss a case of how Gitelman syndrome has presented in the ED and what to learn from it.

Fortuitous Diagnosis Of Total Anomalous Pulmonary Venous Return In A Newborn With Hypoglycemia, Joseph Maes, Terence Zach

Child Health Research Institute Pediatric Research Forum

No abstract provided.

A Novel Approach To Triosephosphate Isomerase Deficiency, Kyra Mccarty

Research Days

Background: Triosephosphate isomerase deficiency (TPID) is a glycolytic pathway enzymopathy causing hemolytic anemia and neurologic dysfunction. TPID is caused by mutations in the TPI1 gene. These patients experience severe hemolytic anemia in infancy followed by progressive neurodegeneration. Diagnosis of TPID is made by measuring decreased TPI enzyme activity elevated dihydroxyacetone phosphate (DHAP) levels in the blood. The diagnosis is confirmed by molecular genetic testing. Neurological involvement typically manifests between 6 and 24 months of age, causing progressive motor dysfunction. Chronic axonal neuropathy is often present on nerve biopsy, and peripheral neuropathy is evident on electrophysiologic studies. Splenectomy and blood transfusions …

Sigirr Variants Identified In Nec Infants Exaggerate Toll-Like Receptor Mediated Inflammation, Jennie Godwin

Research Days

Background: A key event underlying uncontrolled inflammation in necrotizing enterocolitis (NEC) is pathologic activation of Toll-like receptors (TLR). TLR4 recognizes lipopolysaccharide (LPS), from Gramnegative bacteria, and TLR2 peptidoglycans (PAM3Csyk4, PAM), from Gram-positive bacteria. TLR4 and TLR2 signaling events induce an inflammatory cascade through NF-kB, a cytokine inducing transcription factor. Single-immunoglobulin interleukin-1-related receptor (SIGIRR) is a major negative regulator of TLR-mediated NF-kB activation. Previous work from our lab suggests that loss of function in SIGIRR may predispose to NEC. Our lab has identified four variants in NEC patients predicted to alter function of SIGIRR. We hypothesized that identified SIGIRR variants will …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Development Of A Nurse Practitioner Driven Program For Cardiology Providers To Increase Knowledge And Awareness Of Neurodevelopmental Assessment Needs In Children With Congenital Heart Defects, Michele Readman

Doctor of Nursing Practice Final Manuscripts

Children diagnosed with congenital heart defects are at increased risk for neurodevelopmental delays. Timely referral of patients to a neurodevelopmental clinic for initial evaluation and referrals to support services can improve learning outcomes, provide early intervention for neurodevelopmental disorders, and mediate factors affecting low quality of life. Nationally, a substantial proportion of pediatric cardiologists are not referring children for neurodevelopmental evaluation. A review of patient referrals to a Cardiac Neurodevelopmental Clinic within an urban children’s hospital demonstrated an opportunity to improve provider awareness and knowledge of referral recommendations. Using the Iowa Model of Evidence-Based Practice to Promote Quality Care, an …

Increasing Awareness Of Hereditary Fructose Intolerance: An Evidence-Based Practice Implementation Project, Jacqueline M. Bridge

DNP Projects

Background: Hereditary Fructose Intolerance (HFI) is an inborn error of metabolism which results in the absence of an effective Aldolase B enzyme. Without this enzyme, ingestion of fructose and metabolic precursors leads to acute illness, multiorgan damage, and possible death. The increased presence of these sugars results in earlier onset of symptoms and more difficulty for those with HFI.

Purpose: The project’s aim is to increase awareness of HFI in healthcare providers using a learning module and assessments of knowledge at three different points in time.

Methods: The IOWA model for evidence-based practice projects was applied during the development and …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

Honors Scholar Theses

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Assessing The Impact Of Camp Phever On Blood Phenylalanine Levels, Michelle Zelnick

Dissertations and Theses (Open Access)

Phenylketonuria (PKU) is a metabolic disorder that results in accumulation of the amino acid, phenylalanine, throughout the body. This can result in neurocognitive complications if individuals with this disease do not follow a low-protein diet. Camp PHEver is a weeklong summer camp that gives children with PKU an opportunity to obtain skills related to diet compliance, but also enhance their confidence, relationship development, and independence. Through learned skills and the strict diet regimen at camp, campers were found to have a statistically significant drop in phenylalanine (PHE) levels within a single attendance (mean decrease per year range = 2.1 to …

An Exploration Of Psychological Trauma And Positive Adaptation In Adults With Congenital Heart Disease During The Covid-19 Pandemic, Liza Morton Dr, Calum Calderwood, Nicola Cogan, Claire Murphy, Evan Nix, Jacek Kolacz Dr

Patient Experience Journal

The growing population of adults with congenital heart disease (CHD) often have lifelong experience of dealing with potentially traumatic health crises and medical uncertainty whilst facing increased vulnerability to post-traumatic stress disorder (PTSD). The COVID-19 pandemic presents additional challenges for this population including increased risk of health complications, shielding and strict social distancing, changes to medical care provision and social stigma. Despite such challenges, adults with CHD have the potential to also experience positive changes, yet little is known as to what helps cultivate positive adaptation and post-traumatic growth (PTG) within this context. The current study comprised a cross-sectional, anonymous, …