• The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth.

      Lynch, Sally Ann; Foulds, Nicola; Thuresson, Ann-Charlotte; Collins, Amanda L; Annerén, Göran; Hedberg, Bernt-Oves; Delaney, Carol A; Iremonger, James; Murray, Caroline M; Crolla, John A; et al. (2011-05)
      We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.
    • Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

      McCarron, Mark; Reen, Denis J; Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin,, Ireland. mark.mccarron@ucd.ie (2012-02-01)
      In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate's natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.
    • Acute Cerebellitis associated with Dual Influenza A (H1N1) and B infection

      I Hackett, I; O’Sullivan, R; Zaid, AA; Rea, D; Walsh, S (Irish Medical Journal, 2013-03)
      We describe the case of a 6-year old girl who presented to our Emergency Department (ED) with acute onset of ataxia and speech disturbance. Investigative workup included a nasopharyngeal aspirate (NPA) which was influenza A (H1N1) and B positive during the 2010/2011 influenza season. Magnetic resonance imaging (MRI) of the brain confirmed findings consistent with cerebellitis.
    • Agenesis of the corpus callosum with midline lipoma associated with an Xp22.31-Xp22.12 deletion.

      Baker, Louise Brigid; Conroy, Judith; Donoghue, Veronica; Mullarkey, Marice; Shah, Naisha; Murphy, Nuala; Murphy, John; Ennis, Sean; Lynch, Sally Ann; Children's University Hospital, Crumlin, Dublin, Ireland. (2012-02-01)
    • Alveolar lymphangioma in infants: report of two cases.

      FitzGerald, Kirsten; Barry, Siobhán; Fleming, Pádraig; Dental Dept., Our Lady's Children's Hospital, Crumlin, Dublin 12. kirsten.fitzgerald@olchc.ie (Irish Dental Association, 2009-06)
      The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children's hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.
    • Alveolar lymphangioma in infants: report of two cases.

      FitzGerald, Kirsten; Barry, Siobhan; Fleming, Padraig; Dental Dept., Our Lady's Children's Hospital, Crumlin, Dublin 12., kirsten.fitzgerald@olchc.ie (2012-02-01)
      The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children's hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.
    • Anaesthetic implications of laparoscopic splenectomy in patients with sickle cell anaemia.

      Doodnath, R; Gillick, J; Doherty, P; Our Lady's Children's Hospital, Crumlin, Dublin 12. rdoodnath@gmail.com (2012-02-01)
      With the increasing immigrant population in the Republic of Ireland, the number of patients with sickle cell disease (SCD) seen in the paediatric hospitals is climbing. In this case report, we review the anaesthetic implications and outcome of the first two paediatric patients with SCD to have a laparoscopic splenectomy due to repeated splenic infarcts in the Republic of Ireland.
    • Analysis of factors influencing admission to intensive care following convulsive status epilepticus in children.

      Tirupathi, Sandya; McMenamin, Joseph B; Webb, David W; Department of Neurosciences, Our Lady's Hospital for Children, Crumlin, Dublin, 12, Ireland. (2012-02-01)
      OBJECTIVES: To identify clinical features and therapeutic decisions that influence admission to the Intensive Care unit (ICU) in children presenting with convulsive status epilepticus (CSE). METHODS: We evaluated 47 admissions with status epilepticus to a tertiary paediatric hospital A&E over a three year period (2003-2006). Following initial management 23 episodes required admission to ICU and 24 were managed on a paediatric ward. We compared clinical, demographic data and compliance with our CSE protocol between the ICU and ward groups. RESULTS: Median age at presentation in the ICU group was 17 months (range 3 months-11 years) compared to 46 months in the ward group (range 3 months-10 years). Fifty per cent of patients in both groups had a previous history of seizures. Median duration of pre-hospital seizure activity was 30 min in both groups. More than two doses of benzodiazepines were given as first line medication in 62% of the ICU group and 33% of the ward group. Among children admitted to ICU with CSE, 26% had been managed according to the CSE protocol, compared to 66% of children who were admitted to a hospital ward. Febrile seizures were the most common aetiology in both groups. CONCLUSION: Younger age at presentation, administration of more than two doses of benzodiazepines and deviation from the CSE protocol appear to be factors which influence admission of children to ICU. Recognition of pre-hospital administration of benzodiazepines and adherence to therapeutic guidelines may reduce the need for ventilatory support in this group.
    • Analysis of postoperative clinical and nutritional outcomes in a cohort of adolescents following major spinal corrective surgery

      Tarrant, R C; Harrington, M; Kiely, P J; The Department of Orthopaedic Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12 (2011-04)
      INTRODUCTION This retrospective audit aimed to investigate postoperative complications and nutritional outcomes in a cohort of adolescent idiopathic scoliosis (AIS) and Scheuermann’s Kyphosis (SK) cases following major spinal corrective surgery. METHODS Demographic, biochemical, surgical and nutritional data were retrospectively collected on all the postoperative spinal corrrective AIS and SK cases performed in Our Lady’s Children’s Hospital (OLCHC) and the Blackrock Clinic during 2010. SPSS® was used to analyse the data. RESULTS In total, 40 spinal corrective procedures were performed in OLCHC (n=14) and the Blackrock Clinic (n=26) from Jan-Nov 2010 (mean age: 14.9 yrs; 95% AIS). The majority of subjects experienced minor postoperative complications (constipation, 92.5%; vomiting, 65%); 45% (n=18) were anaemic. Major postoperative complications included: illeus (n=5, 12.5%), pneumonia (n=4, 10%), pleural effusion (n=2, 5%) and Type I respiratory failure (n=1, 2.5%). From admission to discharge (median 10 days), the proportion of subjects having a body mass index <25th centile increased from 20% to 67.6%, respectively (P < 0.001). Postoperatively, less than one quarter of subjects (23.7%) met > 50% of their daily energy requirements; one patient was given supplementary nutrition support (parenteral). The mean % weight loss during the hospital stay was 8.2% (± SD 3.9). All cases with an available albumin level at discharge (n=24/40) were below normal (<35g/L). There was one hospital re-admission due to wound infection and weight loss. CONCLUSION Major spinal corrective surgery in the AIS/SK population is associated with an increased malnutrition risk which is a well recognised marker of poor outcomes and increased hospital costs. To minimise postoperative weight loss and identify high risk malnutriton cases, nutritionally screening these patients on admission ± dietetic referral, and early initiation of supplementary nutrition postoperatively as appropriate, should be considered in this patient group.
    • Anthropometric characteristics, high prevalence of undernutrition and weight loss: impact on outcomes in patients with adolescent idiopathic scoliosis after spinal fusion.

      Tarrant, Roslyn C; Nugent, Mary; Nugent, Anne P; Queally, Joseph M; Moore, David P; Kiely, Patrick J; Dept. of Orthopaedic Surgery, Our Lady's Children's Hospital, Crumlin, Dublin 12 (SpringerLink, 2015-02-01)
      Abnormal anthropometry including comparably lower weight and body mass index (BMI) in the adolescent idiopathic scoliosis (AIS) population is increasingly recognised, however, no study has examined postoperative weight loss or its clinical relevance in these relatively thin patients. This study aimed to assess perioperative nutritional status as well as clinically severe involuntary weight loss and its impact on outcomes in patients with AIS undergoing posterior spinal fusion (PSF). A further objective was to compare preoperative anthropometric measurements of the current AIS cohort with healthy controls.
    • 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; et al. (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.
    • 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.
    • Atypical Alstrom syndrome with novel ALMS1 mutations precluded by current diagnostic criteria.

      Casey, Jillian; McGettigan, Paul; Brosnahan, Donal; Curtis, Emma; Treacy, Eileen; Ennis, Sean; Lynch, Sally Ann (2014-02)
      We report on clinical and genetic studies in a non-consanguineous Irish sib-pair with infantile dilated cardiomyopathy and retinopathy. A diagnosis of Alström Syndrome (AS) was considered and diagnostic testing pursued. The Alströms gene (ALMS1) is very large (23 exons) and diagnostic testing of mutational hotspots (exon 6, 8 and 10) was negative. Furthermore the siblings were tall and did not have the typical phenotype of nystagmus, photophobia, obesity or hearing loss and so the AS diagnosis was removed. We then sought to identify the causative gene in this family using whole exome sequencing. Unexpectedly, the exome analysis identified novel compound heterozygous ALMS1 mutations in exon 5 (c.777delT:p.D260fs*26) and exon 20 (c.12145_12146insC:p.S4049fs*36) that segregated with the phenotype. Although the siblings show some clinical overlap with AS, their phenotype is not classical. It is plausible that their atypical presentation may be due to the location of the ALMS1 mutations outside the usual mutational hotspots. Our findings show how atypical cases of AS may be missed under the current diagnostic guidelines and support consideration of complete ALMS1 sequencing in children with two or more features, even if all of the core clinical features of AS are not present.
    • Atypical locations of retropharyngeal abscess: beware of the normal lateral soft tissue neck X-ray.

      Uzomefuna, Vincent; Glynn, Fergal; Mackle, Tara; Russell, John; Otolaryngology Dept., Our Ladys Children Hospital Crumlin, Dublin 12, Ireland., uzomefuna@live.ie (2012-02-01)
      Retropharyngeal abscesses (RPA) are uncommon but potentially lethal deep neck space infections, over 95% of which occur in children under six years of age. Without a high index of suspicion, early recognition and prompt intervention, catastrophic consequences can ensue, and mortality can be as high as 60% if jugular vein thrombosis or mediastinitis occurs. While older children may have specific complaints referable to the pharynx, infants and young children may present with vague symptoms. To date, a lot of emphasis continues to be placed on the importance of lateral soft tissue neck X-ray in the diagnosis and management of patients with suspected retropharyngeal abscesses; and lateral neck X-ray has been cited as the most useful radiological view of the laryngopharynx. While we recognise the role of lateral neck X-rays in retropharyngeal and other upper airway pathologies, we present three case series in which lateral neck X-rays were normal and diagnosis was made only after CT scanning. These three cases were unusual as the abscesses were located high in the naso-pharynx making them impossible to detect on the lateral soft tissue neck X-rays and this underscores the need for high index of suspicion and prompt CT or MRI scanning, in any child with symptoms or signs suggestive of a possible retropharyngeal abscess.
    • An Audit of Paediatric Organ and Tissue Donation in Ireland

      Marshall, L; Hennessey, I; Lynch, C; Gibbons, C; Crowe, S; 1. Our Lady’s Children’s Hospital Crumlin 2. Temple Street Children’s University Hospital 3. Organ Donation and Transplant Ireland. 4. School of Medicine, University of Dublin, Trinity College, Dublin (Irish Medical Journal, 2018-11)
      Organ donation may be considered in children who die in paediatric intensive care units if certain criteria are met and if their families wish for organ donation. In general organs are donated after death has been confirmed using neurological criteria to diagnose brainstem death (BSD). Donation of organs can also occur in certain circumstances after death has been confirmed using circulatory criteria (DCD). The Intensive Care Society of Ireland has published guidelines on organ donation after brainstem death and more recently on donation after circulatory death1,2. The American College of Critical Care Medicine, The Academy of Royal Medical Colleges and The Australian & New Zealand Intensive Care Society have all also published specific guidelines on the determination of brainstem death in infants and children
    • 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
    • Bannayan-Riley-Ruvalcaba syndrome: a cause of extreme macrocephaly and neurodevelopmental delay.

      Lynch, N E; Lynch, S A; McMenamin, J; Webb, D; Department of Neurosciences, Our Lady's Children's Hospital, Crumlin, Dublin 12, , Ireland. nlynch@rcsi.ie (2012-02-01)
      BACKGROUND: Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant condition characterised by macrocephaly, developmental delay and subtle cutaneous features. BRRS results from mutations in the PTEN gene. In adults, PTEN mutations cause Cowden syndrome where, in addition to the macrocephaly, there is a higher risk of tumour development. Diagnosis of BRRS is often delayed as presentation can be variable, even within families. AIMS: To identify characteristics of this condition which might facilitate early diagnosis. Prompt diagnosis not only avoids unnecessary investigations in the child but potentially identifies heterozygote parents who are at risk of tumour development. METHODS AND RESULTS: Six children with a PTEN mutation were identified. All had extreme macrocephaly. Four parents and a male sibling were found to have a PTEN mutation on subsequent testing. Affected parents had extreme macrocephaly and a history of thyroid adenoma, or breast or skin lesions. All six children had presented to medical attention before the age of 2.5 years (3/6 were investigated as neonates), but the median age at diagnosis was 5 years. Four of the children had multiple investigations prior to identification of a PTEN mutation. CONCLUSION: BRRS should be considered in children with extreme macrocephaly as it is the most consistent clinical feature seen, particularly where there is a family history of macrocephaly.
    • Berry syndrome in association with familial limb malformation.

      Shahdadpuri, R; Prendiville, T; Nolke, L; McMahon, C J; Department of Paediatric Cardiology, Our Lady's Children's Hospital, Crumlin,, Dublin. raveenshahdadpuri@yahoo.com (2012-02-01)
      We describe a newborn boy diagnosed with Berry syndrome consisting of a distal aortopulmonary septal defect, aortic origin of the right pulmonary artery, and interruption of the aorta. The child was noted to have reduplication of the right thumb. The child's mother had a claw malformation of her left hand but a normal cardiovascular status. Genetic analysis for TBX5 and SALL4 mutations were negative in both the patient and his mother. This case describes the first ever report of Berry syndrome in an infant with reduplication of the right thumb and familial limb malformation.
    • Burning more than calories: treadmill friction injuries in children.

      Davidson, C C; Eadie, P A; Department of Plastic and Reconstructive Surgery, Our Lady's Children's Hospital,, Crumlin, Dublin. credahan@yahoo.co.uk (2012-02-01)
      Treadmill injuries in young children are a serious but little documented problem. Friction burns occur when the hands come into contact with the moving belt resulting in deep burns that often require hospital admission and surgery. The aim of this study was to assess the nature and prevalence of injuries sustained and to highlight treadmill friction burns as a public health issue previously undocumented in Ireland. A retrospective chart review from January 2006 until March 2008 was performed and functional outcome was assessed by the modified Michigan Hand Outcomes Questionnaire. Eight girls and four boys from one year and seven months to seven years and five months were treated. Eight children required admission to hospital and to date three have required surgery for their injuries. This is a new and increasing problem in Ireland which must be highlighted.
    • Campylobacter jejuni cocultured with epithelial cells reduces surface capsular polysaccharide expression.

      Corcionivoschi, N; Clyne, M; Lyons, A; Elmi, A; Gundogdu, O; Wren, B W; Dorrell, N; Karlyshev, A V; Bourke, B; The Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, 12, Ireland. (2012-02-01)
      The host cell environment can alter bacterial pathogenicity. We employed a combination of cellular and molecular techniques to study the expression of Campylobacter jejuni polysaccharides cocultured with HCT-8 epithelial cells. After two passages, the amount of membrane-bound high-molecular-weight polysaccharide was considerably reduced. Microarray profiling confirmed significant downregulation of capsular polysaccharide (CPS) locus genes. Experiments using conditioned media showed that sugar depletion occurred only when the bacterial and epithelial cells were cocultured. CPS depletion occurred when C. jejuni organisms were exposed to conditioned media from a different C. jejuni strain but not when exposed to conditioned media from other bacterial species. Proteinase K or heat treatment of conditioned media under coculture conditions abrogated the effect on the sugars, as did formaldehyde fixation and cycloheximide treatment of host cells or chloramphenicol treatment of the bacteria. However, sugar depletion was not affected in flagellar export (fliQ) and quorum-sensing (luxS) gene mutants. Passaged C. jejuni showed reduced invasiveness and increased serum sensitivity in vitro. C. jejuni alters its surface polysaccharides when cocultured with epithelial cells, suggesting the existence of a cross talk mechanism that modulates CPS expression during infection.