Paediatric genetics is increasingly playing a role in explorations of why a child may not be reaching developmental milestones, while experiencing various health concerns and displaying unusual physical characteristics. The diagnostic processes include close analyses of a child’s body in order to identify ‘clues’ to possible genetic variation. When the genetic variation identified is new and complex there is significant uncertainty about what relationship that variation has to childhood development and what it will mean for a child’s future. This paper, drawing from an ethnographic study of a genetics clinic, explores what versions of childhood difference and normality are produced by genetic explorations marked by uncertainty. The focus is on the significance of visual dynamics within the consultation, in family stories or photographs, and in the images found on websites which catalogue genetic syndromes. Our argument is that inside and outside the clinic the visual interpretations create understandings of the child that at times position him or her as ‘other’, while at other times recognise the child as normal and ‘one of us’. The uncertainty embedded in identifying rare genetic variations enables multiple interpretations to emerge which do not ‘fix’ the child into the category of the ‘genetically other’.
paediatric genetics; family; childhood; disability
Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.
Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist’s review of each patient’s images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios.
MRI; Protocols; Children
Classification of the overall spectrum of congenital heart defects (CHD) has always been challenging, in part because of the diversity of the cardiac phenotypes, but also because of the oft-complex associations. The purpose of our study was to establish a comprehensive and easy-to-use classification of CHD for clinical and epidemiological studies based on the long list of the International Paediatric and Congenital Cardiac Code (IPCCC).
We coded each individual malformation using six-digit codes from the long list of IPCCC. We then regrouped all lesions into 10 categories and 23 subcategories according to a multi-dimensional approach encompassing anatomic, diagnostic and therapeutic criteria. This anatomic and clinical classification of congenital heart disease (ACC-CHD) was then applied to data acquired from a population-based cohort of patients with CHD in France, made up of 2867 cases (82% live births, 1.8% stillbirths and 16.2% pregnancy terminations).
The majority of cases (79.5%) could be identified with a single IPCCC code. The category "Heterotaxy, including isomerism and mirror-imagery" was the only one that typically required more than one code for identification of cases. The two largest categories were "ventricular septal defects" (52%) and "anomalies of the outflow tracts and arterial valves" (20% of cases).
Our proposed classification is not new, but rather a regrouping of the known spectrum of CHD into a manageable number of categories based on anatomic and clinical criteria. The classification is designed to use the code numbers of the long list of IPCCC but can accommodate ICD-10 codes. Its exhaustiveness, simplicity, and anatomic basis make it useful for clinical and epidemiologic studies, including those aimed at assessment of risk factors and outcomes.
Use of PET/MR in children has not previously been reported, to the best of our knowledge. Children with systemic malignancies may benefit from the reduced radiation exposure offered by PET/MR. We report our initial experience with PET/MR hybrid imaging and our current established sequence protocol after 21 PET/MR studies in 15 children with multifocal malignant diseases. The effective dose of a PET/MR scan was only about 20% that of the equivalent PET/CT examination. Simultaneous acquisition of PET and MR data combines the advantages of the two previously separate modalities. Furthermore, the technique also enables whole-body diffusion-weighted imaging (DWI) and statements to be made about the biological cellularity and nuclear/cytoplasmic ratio of tumours. Combined PET/MR saves time and resources. One disadvantage of PET/MR is that in order to have an effect, a significantly longer examination time is needed than with PET/CT. In our initial experience, PET/MR has turned out to be an unexpectedly stable and reliable hybrid imaging modality, which generates a complementary diagnostic study of great additional value.
Children; PET/MR; MR/PET; Oncology; Hybrid imaging
To review clinical aspects of management of tuberculosis (TB) infection and disease in Canadian children in the context of the global TB epidemic and the rising incidence of drug-resistant TB.
Original and review articles pertinent to: epidemiology of TB globally and in Canada; management of latent TB infection and TB disease in children; diagnostic tests for latent TB infection and TB disease; and management of drug-resistant TB disease. Multiple Medline searches were used including combinations of the MeSH terms ‘Tuberculosis*’ (and its multiple subheadings), ‘Child*’, ‘Drug Resistance’, ‘Mycobacterium tuberculosis*’ and ‘Canada/epidemiology*’. Select relevant textbooks were reviewed.
DATA SELECTION AND EXTRACTION:
The articles were analyzed from the perspective of clinicians managing children in Canada today, and from our experience of managing children with TB in Southern Ontario.
TB in Canada is largely a disease of the foreign-born and their children, but continues to occur in aboriginal children. Drug resistance is increasing globally and in Canada. Most children with TB disease in Canada are asymptomatic and found through contact tracing. False positive skin tests are frequent where TB prevalence is low.
Obtain source case drug sensitivities when treating TB contacts and those with latent TB infection. Obtain cultures before treating TB disease and treat disease with at least four antituberculous drugs while awaiting sensitivities. Use Directly Observed Therapy for TB disease. Confine TB skin testing to children at high risk for TB infection or disease, including contacts of infectious patients and recent immigrants. A team approach and infection control measures including environmental controls are important in managing TB disease.
Canada; Drug resistance; Management; Tuberculosis
Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by the diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in the muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81±26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup-defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full-length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.
mitochondrial DNA; mitochondrial diseases; paediatrics; Africa; high-throughput nucleotide sequencing
Hamartomatous polyps of Peutz-Jeghers are mostly found in patients affected by Peutz-Jeghers syndrome (PJS), but they can be rarely encountered in the general population. It is unclear whether a solitary Peutz-Jeghers polyp (PJP) is an incomplete form of PJS or a separate entity. We report a case of solitary PJP in a paediatric patient in whom the other features of PJS were absent. The patient underwent laparotomy due to small bowel intussusception secondary to an ileac polyp. Histological examination showed the characteristic features of PJP, but the patient did not fulfill the WHO criteria for PJS diagnosis (negative family history for PJS and absence of mucocutaneous pigmentation); moreover analysis of the STK11/LKB1 gene did not reveal any genomic abnormality. The clinical and investigative findings in our case suggest that the solitary PJP can be considered a different clinical entity from PJS.
Peutz-Jeghers syndrome; Solitary Peutz-Jeghers polyp; STK11/LKB1 gene
Malaria is a major cause of paediatric morbidity and mortality. As no clinical features clearly differentiate malaria from other febrile illnesses, and malaria diagnosis is challenged by often lacking laboratory equipment and expertise, overdiagnosis and overtreatment is common.
Children admitted with fever at the general paediatric wards at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania from January to June 2009 were recruited consecutively and prospectively. Demographic and clinical features were registered. Routine thick blood smear microscopy at MNH was compared to results of subsequent thin blood smear microscopy, and rapid diagnostics tests (RDTs). Genus-specific PCR of Plasmodium mitochondrial DNA was performed on DNA extracted from whole blood and species-specific PCR was done on positive samples.
Among 304 included children, 62.6% had received anti-malarials during the last four weeks prior to admission and 65.1% during the hospital stay. Routine thick blood smears, research blood smears, PCR and RDT detected malaria in 13.2%, 6.6%, 25.0% and 13.5%, respectively. Positive routine microscopy was confirmed in only 43% (17/40), 45% (18/40) and 53% (21/40), by research microscopy, RDTs and PCR, respectively. Eighteen percent (56/304) had positive PCR but negative research microscopy. Reported low parasitaemia on routine microscopy was associated with negative research blood slide and PCR. RDT-positive cases were associated with signs of severe malaria. Palmar pallor, low haemoglobin and low platelet count were significantly associated with positive PCR, research microscopy and RDT.
The true morbidity attributable to malaria in the study population remains uncertain due to the discrepancies in results among the diagnostic methods. The current routine microscopy appears to result in overdiagnosis of malaria and, consequently, overuse of anti-malarials. Conversely, children with a false positive malaria diagnosis may die because they do not receive treatment for the true cause of their illness. RDTs appear to have the potential to improve routine diagnostics, but the clinical implication of the many RDT-negative, PCR-positive samples needs to be elucidated.
Malaria; Diagnostics; Polymerase chain reaction; Blood microscopy; Rapid diagnostic test; Tanzania; Paediatrics; Fever
The use of unlicensed and "off-label" medicines in children is widespread. Between 50-80% of the medicines currently administered to children have neither been tested nor authorized for their use in the paediatric population which represents approximately 25% of the whole European population. On 26 January 2007, entered into force the European Regulation of Paediatric Medicines. It aims at the quality of research into medicines for children but without subjecting the paediatric population to unnecessary clinical trial. This article addresses ethical and legal issues arising from the regulation and makes recommendations for the framework conditions facilitating the development of clinical research with children.
Quality of patient care in hospitals has been shown to be inconsistent during weekends and night-time hours, and is often associated with reduced patient monitoring, poor antibiotic prescription practices and poor patient outcomes. Poorer care and outcomes are commonly attributed to decreased levels of staffing, supervision and expertise and poorer access to diagnostics. However, there are few studies examining this issue in low resource settings where mortality from common childhood illnesses is high and health care systems are weak.
This study uses data from a retrospective cross-sectional study aimed at “evaluating the uptake of best practice clinical guidelines in a tertiary hospital” with a pre and post intervention approach that spanned the period 2005 to 2009. We evaluated a primary hypothesis that mortality for children with pneumonia and/or dehydration aged 2–59 months admitted on weekends differed from those admitted on weekdays. A secondary hypothesis that poor quality of care could be a mechanism for higher mortality was also explored. Logistic regression was used to examine the association between mortality and the independent predictors of mortality.
Our analysis indicates that there is no difference in mortality on weekends compared to weekdays even after adjusting for the significant predictors of mortality (OR = 1.15; 95% CI 0.90 -1.45; p = 0.27). There were similarly no significant differences between weekends and weekdays for the quality of care indicators, however, there was an overall improvement in mortality and quality of care through the period of study.
Mortality and the quality of care does not differ by the day of admission in a Kenyan tertiary hospital, however mortality remains high suggesting that continued efforts to improve care are warranted.
Children; Pneumonia; Diarrhea; Weekend versus weekday; Quality of health care
To investigate associations between germline genetic variations in the epidermal growth factor receptor (EGFR) and toxicity in paediatric patients treated with gefitinib.
Patients and methods
Gefitinib treatment and toxicity data from 5 paediatric clinical trials were combined. EGFR genotypes evaluated included -191C>A, -216G>T, Arg497Lys, and intron 1 CA sequence repeat number. The genetic variations were evaluated for associations with grade one or greater rash or diarrhoea during the first course of treatment.
The analysis included 110 patients, 60 (55%) with grade one or greater rash and 47 (43%) with grade one or greater diarrhoea. Among patients with the -216 GG (n=51), GT (n=41), and TT (n=16) genotypes, grade one or greater rash occurred in 52.9%, 46.3% and 87.5% of patients (p=0.003, recessive model), respectively. Diarrhoea occurred in 27.5%, 58.5% and 43.8% of patients with respective GG, GT, and TT genotypes (p=0.004, dominant model). The -191C>A, intron 1 CA repeat number, and Arg497Lys genotypes were not significantly associated with either rash or diarrhoea. EGFR -216 and -191 polymorphisms were in linkage disequilibrium (D’=0.66, p=0.01). The haplotype (-191C, -216T) was associated with increased risk for rash (p=0.049), but was not more predictive of rash than the single -216 polymorphism.
These findings indicate that EGFR -216G>T genotype is a predictive marker for the development of skin rash and diarrhoea in paediatric patients treated with gefitinib. Continued investigation of relationships between germline EGFR polymorphisms and the efficacy of EGFR inhibitors in paediatric patients is warranted.
EGFR; gefitinib; paediatric cancer; skin rash; pharmacogenomics; polymorphisms
Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines.
All lines proliferate as adherent monolayers and express glial markers. Copy number profiling revealed complex genomes including amplification and deletions of genes known to be pivotal in core glioblastoma signalling pathways. Expression profiling identified 93 differentially expressed genes which were able to distinguish between the adult and paediatric high grade cell lines, including a number of kinases and co-ordinated sets of genes associated with DNA integrity and the immune response.
These data demonstrate that glioma cell lines derived from paediatric patients show key molecular differences to those from adults, some of which are well known, whilst others may provide novel targets for evaluation in primary tumours. We thus provide the rationale and demonstrate the practicability of using paediatric glioma cell lines for preclinical and mechanistic studies.
Congenital inguinal hernias are a common paediatric surgical problem and herniotomy through a groin incision is the gold standard. Over the last 2 decades minimally invasive surgery (MIS) has challenged this conventional surgery. Over a period, MIS techniques have evolved to making it more minimally invasive – from 3 to 2 and now single port technique. All studies using single port technique are from tertiary care centres. We used a modification of the technique described by Ozgediz et al. and reviewed the clinical outcome of this novel procedure and put forth our experience at a secondary level hospital.
MATERIALS AND METHODS:
Prospective review of 37 hernias in 31 children (29 male and 2 female) (8 months - 13 years) performed laparoscopically by a single surgeon at a single centre between September 2007 and June 2010. Under laparoscopic guidance, the internal ring was encircled extraperitoneally using a 2-0 non-absorbable suture and knotted extraperitoneally. Data analyzed included operating time, ease of procedure, occult patent processus vaginalis (PPV), complications, and cosmesis.
Sixteen right (52%), 14 left (45%) and 1 bilateral hernia (3%) were repaired. Five unilateral hernias (16.66%), all left, had a contralateral PPV that was repaired (P = 0.033). Mean operative time for a unilateral and bilateral repair were 13.20 (8–25) and 20.66 min (17 -27 min) respectively. Only one of the repairs (2.7%) recurred and another had a post operative hydrocoele (2.7%). One case (2.7%) needed an additional port placement due to inability to reduce the contents of hernia completely. There were no stitch abscess/granulomas, obvious spermatic cord injuries, testicular atrophy, or nerve injuries.
Single port laparoscopic inguinal hernia repair can be safely done in the paediatric population. It permits extension of benefits of minimal access surgery to patients being managed at secondary level hospitals with limited resources. The advantage of minimal instrumentation and avoidance of intracorporeal knotting makes it a feasible technique for a secondary care centre.
Laparoscopic repair; paediatric inguinal hernia; single port
To identify somatic mutations in paediatric diffuse intrinsic pontine gliomas (DIPGs), we performed whole genome sequencing of 7 DIPGs and matched germline DNA, and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem paediatric glioblastomas (non-BS-PGs). 78% of DIPGs and 22% of non-BS-PGs contained p.K27M mutation in H3F3A, encoding histone H3.3, or the related HIST1H3B, encoding histone H3.1. An additional 14% of non-BS-PGs had somatic p.G34R H3F3A mutations.
congenital and acquired airway anomalies represent a relatively common albeit challenging problem in a national tertiary care hospital. In the past, most of these patients were sent to foreign Centres because of the lack of local experience in reconstructive surgery of the paediatric airway. In 2009, a dedicated team was established at our Institute. Gaslini's Tracheal Team includes different professionals, namely anaesthetists, intensive care specialists, neonatologists, pulmonologists, radiologists, and ENT, paediatric, and cardiovascular surgeons. The aim of this project was to provide these multidisciplinary patients, at any time, with intensive care, radiological investigations, diagnostic and operative endoscopy, reconstructive surgery, ECMO or cardiopulmonary bypass. Aim of this study is to present the results of the first year of airway reconstructive surgery activity of the Tracheal Team.
between September 2009 and December 2010, 97 patients were evaluated or treated by our Gaslini Tracheal Team. Most of them were evaluated by both rigid and flexible endoscopy. In this study we included 8 patients who underwent reconstructive surgery of the airways. Four of them were referred to our centre or previously treated surgically or endoscopically without success in other Centres.
Eight patients required 9 surgical procedures on the airway: 4 cricotracheal resections, 2 laryngotracheoplasties, 1 tracheal resection, 1 repair of laryngeal cleft and 1 foreign body removal with cardiopulmonary bypass through anterior tracheal opening. Moreover, in 1 case secondary aortopexy was performed. All patients achieved finally good results, but two of them required two surgeries and most required endoscopic manoeuvres after surgery. The most complex cases were the ones who had already been previously treated.
The treatment of paediatric airway anomalies requires a dedicated multidisciplinary approach and a single tertiary care Centre providing rapid access to endoscopic and surgical manoeuvres on upper and lower airways and the possibility to start immediately cardiopulmonary bypass or ECMO.
The preliminary experience of the Tracheal Team shows that good results can be obtained with this multidisciplinary approach in the treatment of complicated cases. The centralization of all the cases in one or few national Centres should be considered.
regarding the evidence base of medicine. Estimates range from 20% to
80% in various specialties, but there have been no studies in
paediatrics. The aim of this study was to ascertain the evidence base
for community paediatrics.
community paediatricians working in clinics and schools in Yorkshire,
Manchester, Teesside, and Cheshire carried out a prospective review of
consecutive clinical contacts. Evidence for diagnostic processes,
prescribing, referrals, counselling/advice, and child health promotion
was found by searching electronic databases. This information was
critically appraised and a consensus was obtained regarding quality and
whether it supported actions taken.
and forty seven consultations and 1149 clinical actions were performed.
Good evidence was found from a randomised controlled trial or other
appropriate study for 39.9% of the 629actions studied; convincing
non-experimental evidence for 7%; inconclusive evidence for 25.4%;
evidence of ineffectiveness for 0.2%; and no evidence for 27.5%.
Prescribing and child health promotion activities had the highest
levels of quality evidence, and counselling/advice had the lowest.
encouraging amount of evidence was found to support much of community
paediatric practice. This study improved on previous research in other
specialties because actions other than medications and surgery were included.
Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.
Paediatric bacterial meningitis is a neurological emergency which, despite advances in medical management, still has a significant morbidity and mortality. Over recent decades new vaccines have led to a change in epidemiology of the disease; however, it remains a condition that requires a high index of suspicion, prompt diagnosis, and early management in the emergency department. New laboratory techniques and clinical tools are aiding the diagnosis of bacterial meningitis, yet some controversies still exist in its management. This paper outlines the changing epidemiology of the disease, current diagnostic techniques as well as controversies and advances in the management of bacterial meningitis in the paediatric population.
Aims: To test the clinical accuracy of a web based differential diagnostic tool (ISABEL) for a set of case histories collected during a two stage evaluation.
Methods: Setting: acute paediatric units in two teaching and two district general hospitals in the southeast of England. Materials: sets of summary clinical features from both stages, and the diagnoses expected for these features from stage I (hypothetical cases provided by participating clinicians in August 2000) and final diagnoses for cases in stage II (children presenting to participating acute paediatric units between October and December 2000). Main outcome measure: presence of the expected or final diagnosis in the ISABEL output list.
Results: A total of 99 hypothetical cases from stage I and 100 real life cases from stage II were included in the study. Cases from stage II covered a range of paediatric specialties (n = 14) and final diagnoses (n = 55). ISABEL displayed the diagnosis expected by the clinician in 90/99 hypothetical cases (91%). In stage II evaluation, ISABEL displayed the final diagnosis in 83/87 real cases (95%).
Conclusion: ISABEL showed acceptable clinical accuracy in producing the final diagnosis for a variety of real as well as hypothetical case scenarios.
Globally, tuberculosis (TB) continues to exact an unacceptably high toll of disease and death among children, particularly in the wake of the HIV epidemic. Increased international travel and immigration have seen childhood TB rates increase even in traditionally low burden, industrialised settings, and threaten to facilitate the emergence and spread of multi-drug resistant strains. While intense scientific and clinical research efforts into novel diagnostic, therapeutic and preventative interventions have focused on TB in adults, childhood TB has been relatively neglected. However, children are particularly vulnerable to severe disease and death following infection, and those with latent infection become the reservoir of disease reactivation in adulthood, fueling the future epidemic. Further research into the epidemiology, immune mechanisms, diagnosis, treatment and prevention of childhood TB is urgently needed. Advances in our understanding of TB in children would provide wider insights and opportunities to facilitate efforts to control this ancient disease.
Paediatrics; Tuberculosis; Diagnostics; Therapeutics; Prevention; Immune response; Future research priorities; Children; Epidemiology
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease that is often familial, characterized by arrhythmias of right ventricular origin, due to transmural fatty or fibrofatty replacement of atrophic myocardium. ARVC is usually diagnosed in the clinical setting between 20 and 40 years of age. The disease is seldom recognised in infancy or under the age of 10, probably because the clinical expression of the disease is normally postponed to youth and adulthood. This review focuses its attention to the pediatric age, defined as the period of life raging from birth to 18 years. During this span of life, ARVC is not so rare as previously supposed and can be identified by applying the same diagnostic criteria proposed for the adult. Ventricular arrhythmias range from isolated ventricular arrhythmias to sustained ventricular tachycardia and fibrillation. Children and adolescents with ARVC must be carefully evaluated and followed-up especially when a family positive history is present, taking into account the high probability during this life-period that asymptomatic affected patients become symptomatic or that arrhythmias worsen during follow-up. The recent identification of the first defective gene opens new avenues for the early identification of affected subjects even when asymptomatic.
Arrhythmogenic Right Ventricular Dysplasia/diagnosis; Arrhythmogenic Right Ventricular Dysplasia/therapy; Arrhythmogenic Right Ventricular Dysplasia/complications; Heart Ventricle/pathology; Magnetic Resonance Imaging; Syncope/etiology; Death; Sudden; Cardiac/etiology; Tachycardia; Ventricular/etiology
Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous inborn errors of metabolism. At present, treatment is available for only one CDG, but potential treatments for the other CDG are on the horizon. It will be vitally important in clinical trials of such agents to have a clear understanding of both the natural history of CDG and the corresponding burden of disability suffered by patients. To date, no multicentre studies have attempted to document the natural history of CDG. This is in part due to the lack of a reliable assessment tool to score CDG’s diverse clinical spectrum. Based on our earlier experience evaluating disease progression in disorders of oxidative phosphorylation, we developed a practical and semi-quantitative rating scale for children with CDG. The Nijmegen Paediatric CDG Rating Scale (NPCRS) has been validated in 12 children, offering a tool to objectively monitor disease progression. We undertook a successful trial of the NPCRS with a collaboration of nine experienced physicians, using video records of physical and neurological examination of patients. The use of NPCRS can facilitate both longitudinal and natural history studies that will be essential for future interventions.
Electronic supplementary material
The online version of this article (doi:10.1007/s10545-011-9325-5) contains supplementary material, which is available to authorized users.
genes for migraine have been proposed
on the basis of their possible
functional role in its pathogenesis.
Genetic polymorphisms have been
evaluated in association studies,
some of which have been suggested
to be susceptibility markers for
adult migraine. To date, however,
none of the identified polymorphisms
in adult migraine susceptibility
have been investigated in
children, raising the possibility that
they may not be necessarily
involved in paediatric migraine susceptibility.
This paper reviews studies
of the genetic basis of migraine
and summarises our experience in
genetic association studies in primary
paediatric headache susceptibility.
Paediatric migraine; Susceptibility; Polymorphism; Endothelin type A receptor
Background: An increased incidence of paediatric Crohn’s disease was reported recently by our group.
Aims: To assess the incidence and characteristics of inflammatory bowel disease (IBD) in northern Stockholm between 1990 and 2001.
Methods: All records of individuals 0–15 years of age with suspected IBD in the population based catchment area of 180 000 individuals were scrutinised using defined diagnostic criteria. Patient files were searched for relatives with IBD, and for concomitant autoimmune diseases.
Results: A total of 152 children were diagnosed with IBD, corresponding to an overall incidence (per 100 000) of IBD of 7.4. The incidence of Crohn’s disease (CD) was 4.9, ulcerative colitis (UC) 2.2, and indeterminate colitis 0.2. Between 1990 and 2001, there was a marked increase in the incidence of CD while the incidence of UC was almost unchanged, leading to a net increase in the overall occurrence of IBD. There was a male dominance of CD. Fourteen per cent and 11% of patients with CD and UC, respectively, had a first or second degree relative with IBD. Eighteen per cent and 10% of patients with CD and UC, respectively, had a concomitant autoimmune disease. Ten patients with CD (10%) underwent surgery.
Conclusions: The incidence of CD has increased in northern Stockholm. The current incidence is higher than that reported from other areas. Our results suggest a shift in presentation and diagnosis from UC towards CD, but also a net increase in IBD. Concomitant autoimmune disorders and family history are common in paediatric IBD.
Crohn’s disease; epidemiology; inflammatory bowel disease; ulcerative colitis