Research by staff affiliated to Our Lady's Children's Hospital Crumlin

Recent Submissions

  • Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

    Gobius, Ilan; Morcom, Laura; Suárez, Rodrigo; Bunt, Jens; Bukshpun, Polina; Reardon, William; Dobyns, William B; Rubenstein, John L R; Barkovich, A James; Sherr, Elliott H; Richards, Linda J (CellPress, 2016)
    The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.
  • Hidden Costs in Paediatric Psychiatry Consultation Liaison Services

    Kehoe, C; McNicholas, F (Irish Medical Journal, 2018-03)
    It is recognised that children attending paediatric services have an increased rate of mental health (MH) problems1. Hospital based Mental Health services, interchangeably termed Psychiatric Consultation Liaison Services (PCLS), or Psychological Medicine, exist in the large hospitals, and collaborate with their paediatric colleagues, offering assessment and intervention as required. However, PCLS may also have a role in providing Emergency MH assessments for young people presenting to the Emergency Department (ED), a role independent of their paediatric colleagues. In some cases, these children will need to be admitted to an acute paediatric bed for the management of their mental health illness or psychological distress, awaiting transfer to a child psychiatry specialised bed, or discharge to community services. The profile and costs of these cases are inadequately captured by both HSE CAMHS Annual Reporting System3,4 and the Healthcare Pricing Office (HIPE)2 as they often inadequately record MH referrals. This study explores the costs associated with a cohort of patients presenting to a large paediatric hospital ED, and managed by PCLS, in a one-year period.
  • Kawasaki Disease – A Review of Treatment and Outcomes in an Irish Paediatric Cohort 2010-14.

    Flinn, AM; Gavin, PJ; McMahon, CJ; Oslizlok, P; Butler, KM (Irish Medical Journal, 2018-02)
    Diagnosis of Kawasaki Disease (KD) can be challenging due to lack of a diagnostic test, and some children present with ‘incomplete’ KD when not all diagnostic criteria are met. Treatment with intravenous immunoglobulin (IVIG) and aspirin reduces the risk of coronary artery complications. There is sub-group of patients who are resistant to IVIG/aspirin therapy and are at increased risk of complications. Recent evidence suggests that additional treatment of this high-risk group with corticosteroids is beneficial in reducing this risk. We examine the treatment and coronary artery outcomes, by retrospective review of medical records, of a cohort of 32 paediatric patients with KD admitted to a single Irish tertiary centre from January 2010-December 2014. Twenty-eight percent of patients (9/32) had an incomplete diagnosis of KD; these patients received IVIG later compared to those with a complete KD diagnosis. 15/32 (47%) had abnormal echocardiogram findings in the acute phase, 8/32 (25%) had echocardiogram abnormalities at 6-week follow-up, and 4/32 (12.5%) had persisting abnormalities. This study highlights the potential for adverse outcome in KD, the difficulty in diagnosis in ‘incomplete’ cases, and the need to identify children at higher risk for adverse outcome where adjunctive therapies would be most beneficial.
  • Post-Chemotherapy Retroperitoneal Lymph Node Dissection in Patients with Non-Seminomatous Germ Cell Tumour (NSGCT)

    Ariffin, Nur A; Nason, Gregory J; Omer, Shawgi I; Considine, Shane W; Sweeney, Paul; Power, Derek G (Irish Medical Journal, 2017-11)
    Testicular cancer is the most common neoplasm in 20- to 35-year-old men and accounts for one percent of all male neoplasms1,2. It has an incidence of 6.2 per 100,000 per year and an overall mortality of 0.3 deaths per 100,000 per year in the Irish male population3. It is also one of the most curable malignant conditions and has become a model for the multimodal management of malignancies4. Metastases from testicular cancer follow a predictable path via lymphatic spread to the retroperitoneal lymph nodes5. The primary treatment of nodal disease is platinum-based chemotherapy. Twenty to fifty percent of patients have metastatic disease after chemotherapy, in the form of significant residual retroperitoneal disease. In this subset of patients, surgical resection of the residual disease burden plays an important part.
  • The Role of Screening for Coeliac Disease in Asymptomatic Individuals

    Kernan, R; Hussey, S (Irish Medical Journal, 2017-11)
    Coeliac Disease (CD) is a genetically linked autoimmune disorder in which ingestion of gluten causes an immune-mediated reaction in the small intestine, leading to either gastrointestinal malabsorptive symptoms or non-gastrointestinal features including anaemia, Vitamin D deficiency, fatigue and growth failure in childhood. Ireland’s rising incidence of CD likely represents a true increase in disease, correlating with emerging epidemiological data from Scotland and North America
  • Atresia Hymenalis with Haematometrocolpos: A Benefit of Teaching a Case Series and Review of the Literature

    Whitla, L; Jones, J; Barrett, MJ; O’Donnell, SM; Walsh, S; Blackburn, C (Irish Medical Journal, 2017-09)
    Imperforate hymen or atresia hymenalis is a rare clinical presentation, the condition is estimated to be present in 0.5/1000 females1. It is the most common obstructive anomaly of the female genital tract, and results from failure of canalization of the vaginal plate in utero. Atresia hymenalis can present in neonates as bulging hymen due to accumulation of secretions by the uterovaginal mucosa2,3. Usually the imperforate hymen is asymptomatic until menarche, when haematometrocolpos results in symptoms such as abdominal pain, abdominal mass, urinary retention and constipation. Many cases are diagnosed in the evaluation of primary amenorrhoea or recurrent abdominal pain2,3. We present 4 cases diagnosed over a 7 month period in our ED.
  • Vaccine-Preventable Admissions to an Irish Paediatric Intensive Care

    Doyle, Y; Healy, M; McMahon, C; Crowe, S (Irish Medical Journal, 2017-05)
    In the Republic of Ireland, the schedule of state-funded immunisation for children is comprehensive and includes diphtheria, pertussis, tetanus, pneumococcus, hepatitis B, meningococcus C, haemophilus B, polio, measles, rubella and mumps. Varicella and meningococcal B vaccines are commercially available but are not currently funded by the government. Each of the illnesses preventable by these vaccines can cause substantial morbidity, and rarely mortality, in infants and children. Our PICU continues to see serious illness due to avoidable infection. There were 39 admissions in a 4 year period, with 34 children surviving to discharge. Nine children were infected with pneumococcus, with 4 deaths. There was one case of pertussis, causing death. Most infections occurred in previously healthy children. These preventable conditions represent a significant burden on children, families, and on social and healthcare resources
  • First tooth, first visit, zero cavities: a practical approach to the infant oral health visit

    Fitzgerald, Kirsten; McGovern, Eleanor; Ní Chaollaí, Aifric (Journal of the Irish Dental Association, 2017-04)
    The IDA adopted a formal policy on children’s oral health in 2011. There is increasing evidence to support early dental visits for children. The background to the infant oral health visit is discussed and a systematic approach to the practicalities of the visit is offered. General dental practitioners are encouraged to offer the first oral health visit before the first birthday, and this paper aims to give them practical advice concerning this visit. The feature is accompanied by a companion paper that reviews the literature pertaining to the topic, and serves to complement the recent clinical feature published in the Journal of the Irish Dental Association.
  • Difficulties in the Diagnosis and Management of Paediatric Posterior Circulation Stroke

    Walsh, Ó; Mc Coy, B; Rea, D; Webb, D (Irish Medical Journal, 2016-03)
    We present two children with posterior circulation stroke (PCS) highlighting the wide spectrum of presentation, the need for complete radiological assessment, and the relatively high recurrence risk.
  • Dilated cardiomyopathy secondary to vitamin D deficiency and hypocalcaemia in the Irish paediatric population. A case report.

    Glackin, S; Mayne, P; Kenny, D; McMahon, CJ; Cody, D (Irish Medical Journal, 2017-03)
    We identified three infants with dilated cardiomyopathy (DCM) secondary to severe vitamin D deficieny and hypocalcaemia. All infants were exclusively breast fed, from dark skinned ethnic backgrounds, born and living in Ireland. None of these pregnant mothers or infants received the recommended vitamin D supplementation. Each infant presented in heart failure and required inotropic support as well as calcium and vitamin D replacement. Cardiac function subsequently improved. This highlights the public health issue that many high risk pregnant mothers and infants are not receiving the recommended vitamin D supplementation.
  • NSD1 mutations generate a genome-wide DNA methylation signature.

    Choufani, S; Cytrynbaum, C; Chung, B H Y; Turinsky, A L; Grafodatskaya, D; Chen, Y A; Cohen, A S A; Dupuis, L; Butcher, D T; Siu, M T; Luk, H M; Lo, I F M; Lam, S T S; Caluseriu, O; Stavropoulos, D J; Reardon, W; Mendoza-Londono, R; Brudno, M; Gibson, W T; Chitayat, D; Weksberg, R (Nature Publishing Group, 2015-12-22)
    Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1(+/-)-specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive NSD1(+/-) signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing.
  • MUTYH-Associated Polyposis: The Irish Experience

    McVeigh, TP; Duff, M; Carroll, C; Cody, N; O’Shea, R; Bradley, L; Farrell, M; Gallagher, DJ; Clabb, C; Green, AJ (Irish Medical Journal, 2016-11)
    MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH". Phenotypic and genotypic details were obtained by chart review. Bi-allelic mutations were confirmed in 26 individuals (17 families), of whom 16 (62%) developed colorectal malignancies, and 22(85%) polyposis. Eleven families had bi-allelic status for one/both common European mutations. Regional variation was noted, with over-representation of bi-allelic mutation carriers in the South-west of Ireland. MAP is under-diagnosed in Ireland. Increased awareness is required to facilitate appropriate identification and surveillance of bi-allelic mutation carriers for colorectal pathology.
  • Baby steps: a systematic approach to the infant oral health visit

    FitzGerald, Kirsten; McGovern, Eleanor; Ní Chaollaí, Aifric; Duane, Brett (Irish Dental Assocation (IDA), 2016-06)
    For practitioners who wish to offer the infant oral health visit in their practice, some new knowledge and skills may be needed, and it is hoped that the following advice and systematic approach will facilitate both practitioner and family. The visit should include a formal caries risk assessment, which is generally best achieved with the aid of a tool such as the Caries Risk Assessment Checklist (CRAC),1 which is suitable for all children, or a specific tool aimed at the 0-3 age group, such as the American Academy of Pediatric Dentistry’s (AAPD) Caries-risk Assessment Tool (CAT).2
  • Further delineation of the KAT6B molecular and phenotypic spectrum.

    Gannon, Tamsin; Perveen, Rahat; Schlecht, Hélene; Ramsden, Simon; Anderson, Beverley; Kerr, Bronwyn; Day, Ruth; Banka, Siddharth; Suri, Mohnish; Berland, Siren; Gabbett, Michael; Ma, Alan; Lyonnet, Stan; Cormier-Daire, Valerie; Yilmaz, Rüstem; Borck, Guntram; Wieczorek, Dagmar; Anderlid, Britt-Marie; Smithson, Sarah; Vogt, Julie; Moore-Barton, Heather; Simsek-Kiper, Pelin Ozlem; Maystadt, Isabelle; Destrée, Anne; Bucher, Jessica; Angle, Brad; Mohammed, Shehla; Wakeling, Emma; Price, Sue; Singer, Amihood; Sznajer, Yves; Toutain, Annick; Haye, Damien; Newbury-Ecob, Ruth; Fradin, Melanie; McGaughran, Julie; Tuysuz, Beyhan; Tein, Mark; Bouman, Katelijne; Dabir, Tabib; Van den Ende, Jenneke; Luk, Ho Ming; Pilz, Daniela T; Eason, Jacqueline; Davies, Sally; Reardon, Willie; Garavelli, Livia; Zuffardi, Orsetta; Devriendt, Koen; Armstrong, Ruth; Johnson, Diana; Doco-Fenzy, Martine; Bijlsma, Emilia; Unger, Sheila; Veenstra-Knol, Hermine E; Kohlhase, Jürgen; Lo, Ivan F M; Smith, Janine; Clayton-Smith, Jill (Nature Publishing Group, 2015-09)
    KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed.
  • The efficacy of an extended scope physiotherapy clinic in paediatric orthopaedics.

    O Mir, Marie; Cooney, Ciara; O'Sullivan, Cliona; Blake, Catherine; Kelly, Paula; Kiely, Pat; Noel, Jacques; Moore, David (Journal of children's orthopaedics, 2016-04)
    The demand for paediatric orthopaedic care is growing, and providing the service required is an increasingly challenging task. Physiotherapist-led triage clinics are utilised in adult orthopaedics to enable the provision of care to patients who may not require a surgical consult. The Physiotherapy Orthopaedic Triage Clinic (POTC) was established in Our Lady's Children's Hospital Crumlin in response to increasing demands on the paediatric orthopaedic service. The clinic is run by physiotherapists working in an advanced practice role (APP), and is the first paediatric clinic of its type and scale in the Republic of Ireland.
  • Preoperative curves of greater magnitude (>70°) in adolescent idiopathic scoliosis are associated with increased surgical complexity, higher cost of surgical treatment and a delayed return to function

    Tarrant, R. C.; Queally, J. M.; O’Loughlin, P. F.; Sheeran, P.; Moore, D. P.; Kiely, P. J.; Our Lady's Children's Hospital Crumlin; National Children's Research Centre Dublin 12 (2016-01-07)
  • A paediatric hernia with a twist: the presentation, imaging findings and management of a strangulated ovarian hernia

    Hughes, P; Abdelhafeez, A; Byrne, AT; Rea, D; JGillick, J (Irish Medical Journal, 2015-10)
    Indirect inguinal hernias are the most commonly encountered congenital abnormality in infants. 1,2 They may be complicated by herniation of abdominal or pelvic viscus. In girls, a herniated ovary is a relatively common finding, however torsion of the ovary is infrequent. A tender irreducible inguinal hernia in an infant girl should raise the possibility of a strangulated herniated ovary as it requires urgent surgical attention. When in doubt, ultrasound with colour Doppler easily confirms the diagnosis. Here we present the case of an ovarian inguinal hernia which had undergone torsion and review the presentation, imaging findings and management.
  • Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia.

    Niemeyer, Charlotte M; Loh, Mignon L; Cseh, Annamaria; Cooper, Todd; Dvorak, Christopher C; Chan, Rebecca; Xicoy, Blanca; Germing, Ulrich; Kojima, Seiji; Manabe, Atsushi; Dworzak, Michael; De Moerloose, Barbara; Starý, Jan; Smith, Owen P; Masetti, Riccardo; Catala, Albert; Bergstraesser, Eva; Ussowicz, Marek; Fabri, Oskana; Baruchel, André; Cavé, Hélène; Zwaan, Michel; Locatelli, Franco; Hasle, Henrik; van den Heuvel-Eibrink, Marry M; Flotho, Christian; Yoshimi, Ayami; Our Ladys Hospital Crumin, Dublin (Haematologica, 2015-01)
    Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I-II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia.
  • Sickle cell disease: time for a targeted neonatal screening programme.

    Gibbons, C; Geoghegan, R; Conroy, H; Lippacott, S; O'Brien, D; Lynam, P; Langabeer, L; Cotter, M; Smith, O; McMahon, C (Irish Medical Journal, 2015-02)
    Ireland has seen a steady increase in paediatric sickle cell disease (SCD). In 2005, only 25% of children with SCD were referred to the haemoglobinopathy service in their first year. A non-funded screening programme was implemented. This review aimed to assess the impact screening has had. All children referred to the haemoglobinopathy service born in Ireland after 2005 were identified. Data was collected from the medical chart and laboratory system. Information was analysed using Microsoft Excel. 77 children with SCD were identified. The median age at antibiotic commencement in the screened group was 56 days compared with 447 days in the unscreened group, p = < 0.0003. 22 (28%) of infants were born in centre's that do not screen and 17 (81%) were over 6 months old at referral, compared with 14 (21%) in the screened group. 6 (27%) of those in the unscreened group presented in acute crisis compared with 2 (3%) in the screened population. The point prevalence of SCD in Ireland is 0.2% in children under 15 yr of African and Asian descent. We identified delays in referral and treatment, which reflect the lack of government funded support and policy. We suggest all maternity units commence screening for newborns at risk of SCD. It is a cost effective intervention with a number needed to screen of just 4 to prevent a potentially fatal crisis.
  • Influence of curve magnitude and other variables on operative time, blood loss and transfusion requirements in adolescent idiopathic scoliosis.

    Nugent, M; Tarrant, R C; Queally, J M; Sheeran, P; Moore, D P; Kiely, P J; Our Lady's Children's Hospital Crumlin; National Children's Research Centre Dublin 12 (2015-05-03)
    Posterior spinal instrumentation and fusion for correction of adolescent idiopathic scoliosis (AIS) typically requires lengthy operating time and may be associated with significant blood loss and subsequent transfusion. This study aimed to identify factors predictive of duration of surgery, intraoperative blood loss and transfusion requirements in an Irish AIS cohort.

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