Children's Mercy Hospital Research Articles

A Feasibility Study of a Music Enrichment Program on Relative Reinforcing Value of Food and Home Environmental Enrichment among Families of Low Socioeconomic Status.

Emerging evidence suggests that low socioeconomic status (SES) home environments may play a role by promoting excess energy intake through a lack of access to non-food reinforcers. Because of the deleterious effects of SES-related disparities on child health and development, feasible and culturally acceptable interventions are urgently needed. Community-based music enrichment programs may be an ideal intervention strategy. In collaboration with a local non-profit organization and music studio, we conducted a pilot randomized controlled trial to assess the effects of a music enrichment program versus a play date control in a group of 9-24-month-old healthy infants (N = 16). The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Children's Mercy Hospital Kansas City. This study is registered with clinicaltrials.gov (NCT05868811). Overall, we found some intervention effects on the relative reinforcing value of food (RRVfood) and the home environmental enrichment measures (i.e., increased music use at home and the home language environment). Our intervention demonstrated large effects on the increased use of music at home. We did not find significant group differences in the RRVfood and home language environment, but some of the effect sizes were medium-to-large. Results also suggest that our intervention is feasible and acceptable. Parent feedback indicated that the intervention was well-liked and that the steps we took to help reduce barriers worked. Music enrichment programs may be a high-impact, low-cost strategy to address socioeconomic disparities.

Implementing a Halo Gravity Traction Program: A Multidisciplinary Endeavor.

Halo gravity traction (HGT) is a preoperative modality for children with severe spinal deformity used to optimize spine flexibility and balance while decreasing the likelihood of neurologic injury. HGT is a dependable solution for these challenging spinal deformities. Aligning treatment guidelines and providing resources, education, and training for staff are key components for a successful HGT program. The HGT program at Children's Mercy Hospital was then developed with a systems approach with the holistic goal of multidisciplinary collaboration with physical/occupational therapy, hospital medicine, pulmonology, psychology, nutrition, child life, and complex care management. Education, research, and national collaboration to standardize this therapy should improve patient safety and support quality improvement.

A Review of an Interfacility Transport Program Pediatric Stroke Clinical Practice Guideline.

Pediatric acute ischemic stroke is a rare diagnosis that requires timely recognition and definitive management to prevent morbidity and mortality. Children often present to primary care offices, urgent care clinics, and adult emergency departments for evaluation of symptoms that may be signs and symptoms of stroke. Currently, there are no published prehospital or transport protocols specific to pediatric acute ischemic stroke. The Children's Mercy Hospital Critical Care Transport Team (CMCCT) created a pediatric-specific clinical practice guideline (CPG) for suspected acute ischemic stroke. This retrospective, descriptive study reports pediatric patients aged younger than 18 years who met criteria for the pediatric stroke CPG and required interfacility transport by CMCCT over a 4- year period. Large vessel occlusion (LVO) scores used in adults were calculated retrospectively. Seventeen patients met inclusion criteria. Four (24%) of 17 had radiographic evidence of acute thrombus, 3 of whom received alteplase and/or endovascular clot retrieval. Median age of confirmed stroke was 83 months (interquartile range, 65-148) compared with 177 months for nonstroke (interquartile range, 169-191), P = 0.126. The most common presenting symptom was hemiplegia in the confirmed stroke group. The confirmed stroke group scored significantly lower on the Glasgow Coma Scale (median of 8 vs 15, P = 0.014), significantly higher on the Los Angeles Motor Scale LVO score (median 4 vs 0, P = 0.021), and significantly higher on the Rapid Arterial Occlusion Evaluation LVO (median 4 vs 0, P = 0.036). To our knowledge, the CMCCT CPG is the first pediatric transport protocol aimed at recognition and management of pediatric stroke described in the literature. Retrospective calculation of LVO scores show that they may be helpful in application to pediatric patients.

Editorial introductions.

Editorial introductions.

Analysis of High Flow Nasal Cannula Utilization During Pediatric Critical Care Transport

ObjectiveThere are limited studies on the safety and efficacy of high flow nasal cannula (HFNC) use in pediatrics during interfacility critical care transport. This 15-month retrospective study aims to describe our transport team's utilization of HFNC within the pediatric population and evaluates the need for patient escalation in respiratory support within 24 hours of hospital admission including increased liter flow, transition to noninvasive ventilation, or intubation. MethodsRetrospective charts were reviewed by study members from January 1, 2019, through March 31, 2020. Study dates were specifically chosen to reflect when HFNC was implemented in the transport department and before the beginning of the severe acute respiratory syndrome coronavirus disease 2019 (SARS-COVID-19) pandemic because of variability in respiratory support recommendations at the beginning of the pandemic. Patients were screened for inclusion criteria and were included if they were >30 days and <18 years of age, required HFNC at ≥4 L/min during transport, and were admitted to Children's Mercy Hospital. ResultsDuring the study period, we completed 6,279 pediatric transports, of which 382 had documented HFNC use and 358 met the inclusion criteria. Our HFNC patients had a median age of 0.7 years with an interquartile range (IQR) of 0.3 to 1 year, a median weight of 8.4 kg with an IQR of 6.2 to 11 kg, a median liter flow of 10 L/min and 1.2 L/kg/min, and required a median transport time of 80 minutes with an IQR of 69 to 115 min. Patients were tracked for 24 hours post-admission for any escalations in care; 33% required an escalation, 76% of those had an increase in flow, 24% required noninvasive ventilation, and 0% required intubation. ConclusionOur study suggests HFNC is a safe and effective means for providing respiratory support to the pediatric population during interfacility critical care transport. Our data support utilization of 1 to 2 L/kg/min in the smaller pediatric population (<10 kg) during transport. There was minimal risk of escalation to noninvasive ventilation, and no patients required intubation within 24 hours post drop-off, likely because of the appropriate utilization of HFNC during transport. Additional studies, especially multicenter pediatric studies, are needed to analyze HFNC utilization with non-restricting circuits and vibrating mesh nebulizers.

Increasing Incentive Spirometry Use in Patients with Sickle Cell Disease Admitted to Children's Mercy Hospital

Introduction: Acute chest syndrome is one of the leading causes of morbidity and mortality in patients with sickle cell disease. The National Heart, Lung, and Blood Institute (NHLBI) recommends providing ten breaths of incentive spirometry (IS) every two hours while awake for patients with sickle cell disease admitted to the hospital to help prevent development of acute chest syndrome. Methods: We reviewed provision of IS at Children's Mercy Hospital (CMH) in Kansas City, Missouri between 08/01/2021 and 11/01/2021. Data were collected and the target population was identified via a report generated from the electronic medical records of those patients admitted with sickle cell disease and vaso-occlusive pain requiring continuous opioid infusion. We reviewed the frequency with which IS was offered each hospital day and found that during that 3-month time period, no patients were offered IS at the frequency recommended by the NHLBI. Meetings with stakeholders identified that IS orders were inconsistent between electronic medical record order sets and were not based on current NHLBI recommendations. To address this potential root cause, order sets were updated to match NHLBI recommendations. We then reviewed provision of IS following implementation of standardized IS orders between 12/21/2021 and 3/14/2022. Our primary aim with our initial plan-do-study-act (PDSA) cycle was to increase the frequency IS was being offered to patients to meet NHLBI guidelines. Results: Between 08/01/2021 and 11/01/2021, there were 285 hospital days with patients admitted to CMH with a sickle cell vaso-occlusive pain. We excluded days of admission and discharge (94 days). Of 191 full hospital days, only 53% (101/191) had IS documented at all. When IS was documented, 0% of patients were offered the recommended frequency of IS and the median time between IS offerings was 6.3 hours. Following implementation of updated orders on 12/21/2021 IS was offered to patients at the recommended frequency 1% of the time, and the median hours between when IS was offered decreased to 5.9 hours. Conclusion: The initial goal of this project was to increase the daily occurrences of IS offered to sickle cell patients admitted to the hospital with vaso-occlusive pain to meet the NHLBI recommended frequency from 0% to 10% over a 3-month period following the implementation of updated IS orders within Cerner powerplans. Further PDSA cycles will continue to refine our approach to increasing frequency IS is offered to the patient and documented in the medical record. Subsequent PDSA cycles will also focus on increasing patient use of IS as well as analyzing supplemental oxygen use before and after each intervention as a patient outcome measure.

Therapeutic plasma exchange for multiorgan dysfunction among critically ill pediatric patients with leukemia: A single-institutional experience.

Therapeutic plasma exchange (TPE) has well-documented applications in the adult population, outlined by the American Society for Apheresis (ASFA) 2019 guidelines. Limited data exist regarding the use of TPE in critically ill pediatric patients; however, these reports rarely include patients with oncological diseases. We highlight the use of TPE in the acute management of seven pediatric patients with leukemia treated at Children's Mercy Hospital ICU from 2015 to 2020, including TPE specifications, baseline and interval laboratory evaluation, and outcome measures. Analysis compared those who did (n=4) and did not (n=3) survive 30 days post-TPE. Multiorgan failure (MOF) prompted the initiation of TPE in 85.7% of patients, 57.1% of whom were also diagnosed with hemophagocytic lymphohistiocytosis (HLH). Baseline laboratory evaluations prior to initiation of TPE were similar between the two groups. With subsequent TPE treatments, C-reactive protein (CRP) and lactic acid decreased. CRP and lactic acid following the last TPE treatment were significantly higher for those deceased 30 days post-TPE (P = .023 and .031, respectively). No TPE-associated adverse events necessitated discontinuation of TPE treatment. Several surviving patients required chemotherapy dose reductions or alterations. Our cohort demonstrated MOF and HLH consistently as indications for TPE, currently ASFA category III indications (optimal role of apheresis is not yet established). Recognition of this treatment modality earlier in the clinical course for critically ill oncological patients may lead to the development of formal protocols that may result in earlier initiation of TPE and improved outcomes.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Demographics in Children Presenting With Acute Neurologic Deficits Concerning for Stroke: An Evaluation of the Stroke Alert Process.

Objective: To assess the demographics and clinical characteristics of children presenting with acute neurologic symptoms concerning for stroke. Background: Stroke leads to significant morbidity in the pediatric population. Stroke protocols were created as a means to help identify and triage these children. Despite implementation of these protocols, there have been few population-based studies evaluating the demographics and clinical features of children presenting with acute strokelike symptoms. Methods: A retrospective chart review of patients for whom the stroke alert process was activated from September 2016 through August 2018 at Children's Mercy Hospital. Results: There were a total of 61 activations. Acute ischemic stroke or transient ischemic attack comprised 18% and was the second leading diagnoses after seizure with postictal (Todd) paralysis (20%). Two activations were candidates for mechanical thrombectomy, and none received tissue plasminogen activator (tPA). Children with acute ischemic stroke / transient ischemic attack were likely to be younger in age (median 4 years, interquartile range [IQR] 3-9) compared to those with nonischemic stroke diagnoses (median 12.5 years, IQR 7-15.3) (P = .010). The anatomical location of acute ischemic stroke was widespread, including both anterior and posterior circulations. Past medical history, family history, racial demographics, sex, and initial presenting symptoms were not predictive of the diagnosis of acute ischemic stroke / transient ischemic attack. 38% of activations with diagnoses other than transient ischemic attack / acute ischemic stroke required urgent treatment, with 16% requiring intensive care unit admission. Conclusion: Acute ischemic stroke / transient ischemic attack comprised nearly one-fifth of all pediatric stroke activations, highlighting the importance of developing protocols for early recognition and evaluation of children who present with symptoms concerning for stroke.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

Ontogeny of Pediatric Pharmacogenetics: Celebrating the Past and Vision for the Future.

A Multi-Institution Retrospective Study to Assess Bleeding Phenotype Among Patients with Platelet Function Disorders

▪Introduction: Platelet function disorders (PFD) clinically manifest with wide variability in mucocutaneous bleeding and significant hemorrhage post-surgery or trauma. The overall prevalence of PFD is not known, as there have not been large population-based studies. Treatment of these patients vary based on their bleeding phenotype. Additionally, the exact bleeding phenotype of many qualitative platelet defects are not well described in literature. This study aims to describe the bleeding phenotype among patients with different (PFD).Methods: This is a retrospective study among patients with PFD conducted at 3 Hemophilia Treatment centers - HOG Center for Bleeding and Clotting Disorders of CHOA, Children's Mercy hospital HTC and Rainbow babies & Children's hospital HTC. Institutional IRB approval was obtained at all 3 institutions. We collected data on demographics, bleeding symptoms at presentation, bleeding episodes, management of these bleeds over a 6-year time period (2015-2020).Results: We identified 131 patients with PFDs at 3 institutions. This included 67 males (51.2%) and 64 females (48.8%). Among 131 patients, 72 patients (55%) had a defect in platelet agonist interaction/receptor defect (ADP/Epinephrine/Collagen/TXA2/Arachidonic acid), 37 patients (28.2%) had delta storage pool defect, 8 patients (6.1%) had Glanzmann thrombasthenia, 7 patients (5.3%) had a platelet release defect, 3 patients (2.3%) with an alpha granule defect, 2 patients (1.5%) with Bernard Soulier syndrome and 1 patient (0.76%) with Wiskott Aldrich syndrome. The most common bleeding symptoms at presentation were epistaxis (40.4%), followed by easy bruising (31.3%), heavy menstrual bleeding (15.2%), gum bleeding (6.87%) and gastrointestinal bleeding (4.58%). From 2015-2020, a total of 162 bleeds were documented, and 68 patients (51.9%) with at least 1 documented episode of bleeding. 67.2% of these bleeds were spontaneous, 12.3% were secondary to trauma, 4.9% after a dental procedure, 2.5% after surgery and 0.6% after child birth. The most common type of bleeding episode in diagnosed patients included epistaxis (50%), heavy menstrual bleeding (17.9%), skin/soft tissue bleed (5.5%), gastrointestinal (5.5%) and dental/tooth related (4.9%). 93 bleeding episodes (57.4%) required some form of treatment in various settings - home (73%), clinic (15%), emergency room (7.5%), hospitalization (14%) and ICU stay (2%). Treatments included antifibrinolytics (68.8%), recombinant factor VIIa (11.8%), desmopressin (9.6%), hormonal therapy (9.6%) and platelet transfusions (5.3%).Conclusions: Our study helps characterize the bleeding phenotype and management in patients with various PFD. This data is crucial in understanding the burden of illness among different types of PFD, and to understand health care utilization to better serve the needs of these poorly characterized patients. DisclosuresSidonio: Sanofi, Takeda, Octapharma, Bayer, Biomain, Grifols, Kedrion, Genentech. Catalyst, Guardian Therapeutics, Novo Nordisk, Hema Biologics, Uniqure.: Consultancy, Honoraria. Silvey: Genentech: Speakers Bureau; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees. Ahuja: XaTek, Inc: Patents & Royalties; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB member ; Genentech: Membership on an entity's Board of Directors or advisory committees.

Implementation of a Scalable Family-Based Behavioral Treatment for Childhood Obesity Delivered through Primary Care Clinics: Description of the Missouri Childhood Obesity Research Demonstration Study Protocol.

Background: Significant gaps exist in access to evidence-based pediatric weight management interventions, especially for low-income families who are disproportionately affected by obesity. As a part of the Centers for Disease Control and Prevention's Childhood Obesity Research Demonstration project (CORD 3.0), the Missouri team (MO-CORD) aims to increase access to and dissemination of an efficacious pediatric obesity treatment, specifically family-based behavioral treatment (FBT), for low-income families. Methods/Design: The implementation pilot study is a multisite matched-comparison group pilot of packaged FBT in pediatric clinics for low-income children with obesity, of ages 5 to 12 years old. The study is implemented in two Missouri pediatric primary care clinical sites, Freeman Health System Pediatric Clinics (rural Joplin) and Children's Mercy Hospital Pediatric Clinics (urban Kansas City). The design focuses on pragmatism through utilization of PRECIS (Pragmatic Explanatory Continuum Indicator Summary) domains, such as open eligibility criteria, limited follow-up intensity, reliance on medical records for creating a usual care comparison group data, and unobtrusive measurement of participant and provider adherence. The evaluation focuses on effectiveness as well as implementation outcomes and barriers to inform implementation scale up. Conclusions: Findings from this study will advance both science and practice by providing novel and immediately useful information to families, health care providers, health care organizations, payers, and other state Medicaid plans by developing and optimizing evidence-based pediatric weight management treatment for implementation and dissemination in health systems to address health disparities among low-income populations most affected by overweight and obesity.

Risks and mitigation strategies to prevent etoposide infusion-related reactions in children.

Etoposide is an antineoplastic agent widely used for treatment of many pediatric cancers. Etoposide has been associated with infusion-related reactions. In this brief report, we compare etoposide infusion-related reactions that occurred over a 10-year period at two freestanding pediatric hospitals. Infusion reactions occurred in 1% of patients at two hospitals across the study period. Rates of 4.8%, 3.4%, and 7.9% were observed at Children's Mercy Hospital during 2018, 2019, and 2020, respectively, after the implementation of in-line filters during etoposide infusions in late 2017. Of the 32 patients who experienced adverse reactions, 41% were rechallenged after the reaction and all were able to tolerate at least one future dose with either pre-treatment or extending infusion duration. This work highlights the importance of a multicenter approach to investigating adverse drug reactions (ADRs) as variation in practice can provide key information about ADRs and potential risk factors.

Pott's puffy tumor in a 23-month-old: Youngest known case of a rare disease

This case report describes a child who developed Pott's puffy tumor and was treated at the Children's Mercy Hospital in Kansas City. In addition to a discussion of a case, a review of the literature was completed on this topic describing the typical embryology and development of the frontal sinus, and the epidemiology, diagnosis, and treatment of Pott's puffy tumor. The patient was a 23-month-old boy who developed Pott's puffy tumor after recovery from influenza. The patient presented to the hospital with progressing edema of the unilateral eye that spread bilaterally within a few days. A CT scan demonstrated pansinusitis, developed frontal sinuses, right periorbital cellulitis, and medial forehead subperiosteal abscess. Functional endoscopic sinus surgery and transcutaneous abscess drainage were urgently performed and the patient made a full recovery following a course of ertapenem and levofloxacin. The presence of a developed frontal sinus in a 23-month-old is an unexpected radiologic finding. This case represents the youngest patient reported in the literature to develop this rare complication of frontal sinusitis.

Editorial introductions.

Editorial introductions.

Bleeding Disorder Referrals to Hematology Clinic: A Single Institution Experience

BACKGROUND Our tertiary care pediatric hematology/oncology/BMT service receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing prior to elective surgery. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurate interpretation of lab results. In 2014, Bhasin et al., Pediatric Hematology and Oncology showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little literature about the referral patterns to pediatric hematology and the outcomes of these referrals. OBJECTIVES To characterize our hematology referrals for bleeding disorder, work up To describe the diagnostic outcomes from these referrals To estimate the proportion of bleeding disorders diagnosed from these referrals To identify referral factors that are associated with being diagnosed with a bleeding disorder DESIGN/METHOD This is a single center, retrospective chart review. Patients referred and or seen for a bleeding disorder evaluation at Children's Mercy Hospital from 07/1/2018 until 06/30/19 were evaluated for demographics, reason for consultation, referring provider, and outcome of referral. Akaike Information Criterion (AIC) was applied to logistic regression to identify factors associated with diagnosis of bleeding disorder. RESULTS A total of 373 patients were included and demographics are detailed in Table 1. Forty patients were diagnosed with a bleeding disorder, 78 patients were lost to follow up or have work up still in progress, and 255 patients had a bleeding disorder ruled out. Of our referred patient sample, 6% (21/373) were diagnosed with von Willebrand disease, 4% (14/373) were diagnosed with a platelet function disorder, and 1.3% (5/373) were diagnosed with a coagulation factor deficiency. The median time between referral and appointment was 31.5 days with a median of 2 total visits including clinic and laboratory visit for a clinical diagnosis. Forty percent of referrals were for preoperative clearance, 36% for family history, and 57% for symptoms. Of the patients referred for symptoms, 22.7% were referred for bruising and 83.9% for bleeding. Thirty eight percent had previously been treated for symptoms through hormone management, nasal cauterization, surgical intervention, or other methods. Forty four percent (164/373) of the referrals were from Otolaryngology, 30% from primary care including adolescent medicine and gynecology, and 27% from other specialties. Seventy percent of referrals were internal from specialties within our institution. The results indicate that the odds of a bleeding disorder diagnosis decrease by 8% for every year increment in age and was 3 times higher among patients having abnormal coagulation labs at the time of referral as compared to their counterpart when other variables were controlled. Logistic regression model showing referral factors that could be associated with bleeding disorder diagnosis are detailed in table 3. CONCLUSION This study characterizes the bleeding disorder referral patterns at our institution including the proportion of bleeding disorders diagnosed. This study also highlighted certain referral factors such as age, gender, referral for preoperative clearance, previous treatment with nasal cauterization and the presence of abnormal lab values that could be predictive of the presence of a bleeding disorder. Limitations of this study include the small number of patients with confirmed diagnosis and that it is conducted at a single center. Additionally, at our center, referrals are screened by a physician prior to being seen, which could have influenced the results. We illustrate that large-scale studies are needed to determine referral factors associated with the diagnosis of a bleeding disorder. Disclosures Carpenter: American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Hemostasis &amp; Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; CSL Behring: Research Funding; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Honoraria; Kedrion: Honoraria; Novo Nordisk: Honoraria.

Transition to Adult Care in Youth with Epilepsy: One Center's Experience with a Transition Program and Its Integration within Telemedicine

AbstractNeurology patients often have disorders that require life-long care and ongoing treatment. The transition of pediatric neurology patients to adult neurology care, particularly in epilepsy, is an evolving concept that is recognized as important for patients and families. Children's Mercy Hospital, Kansas City has an established transition program that has been integrated into the neurology clinic as a part of standard care. Our experience and utilization of a transition program has provided our patients with a unique opportunity, empowering them to navigate their own care and create a seamless transition to adult neurology. Through a collaboration with the American Academy of Pediatrics and the Department of Health Resources and Services Administration, we have proposed a practice model designed to create a medical home for children and youth with epilepsy in rural underserved areas of Kansas. One of the core end points of this study is transition of care for youth with epilepsy using telemedicine. In this article, we describe our experience with a transition program for epilepsy patients and describe the very early implementation of this program to a telemedicine transition program designed for underserved rural populations.

Editorial introductions

Editorial introductions

COLA (Conferences On-Line Allergy) at 10 Years — Evolution of an Online Fellowship Curriculum

Online learning has been present since the early days of the Internet. As with any new technology, users look to make their life easier and to save time. Experts in medical education are no different than other users. They want to adapt new technologies to their fullest. Medical educators have been challenged with keeping education interesting and up to date, while maximizing their resources. The challenges with any online educational program include being able to reach large numbers of learners, having content that is relevant and timely, and having it available thorough many different formats to suit the user. There are many examples of online learning programs in all fields of medicine and many specific to Allergy/Immunology. In this review, we describe a form of real-time videoconferencing referred to as Conferences On-Line Allergy (COLA), which was developed at Children's Mercy Hospital and Clinics. This program, which started as a once a month webinar, has transformed into a well-known curriculum used by many Allergy/Immunology training programs across the United States. It provides not only live interactive conferences but also a library of recorded lectures and workshops that can be used at the learner's convenience. Taking advantage of the generosity of many volunteer presenters, it allows sharing of resources and provides benefits to the Allergy/Immunology community.

A novel nonsense substitution identified in the AMIGO2 gene in an Occulo-Auriculo-Vertebral spectrum patient.

Craniofacial microsmia is the second most common congenital disorder with mostly unilateral defects of ear, temporomandibular joint, mandible, and muscles of facial expression and mastication. The objective of this study was to identify, if there were any, de novo germline or somatic variants in a patient with Occulo-Auriculo-Vertebral Spectrum (OAVS) using whole-exome sequencing. Trio/Family-based study of an OAVS proband. Children's Mercy Hospital Institutional Review Board approved this study and a request-to-rely was procured from the University of Missouri Kansas City IRB. Informed assent/consent was obtained for all family members prior to any research activities. The peripheral blood/affected side tissues from corrective surgery of the proband and peripheral blood samples from unaffected parents were collected. The isolated genomic DNA were enriched for exomes and sequenced on an Illlumina HiSeq 2500 instrument yielding paired-end 125 nucleotide reads (84X coverage). Gapped alignment to reference sequences (GRCh37.p5) was performed with BWA and the GATK and analysis completed using custom-developed software. Analyses revealed that the proband carried a de novo germ line nonsense substitution (c.901C>T) in AMIGO2 gene, and missense substitutions in ZCCHC14 (c.1198C>T), and in SZT2 genes (c.2951C>T). The nonsense substitution in AMIGO2 gene introduces a premature stop codon possibly rendering the gene non-functional via nonsense-mediated pathway decay-therefore considered a stronger candidate. Further functional studies are required to confirm whether loss-of-function variants in AMIGO2 can cause OAVS.