共查询到20条相似文献,搜索用时 15 毫秒
1.
Bergmann C 《European journal of pediatrics》2012,171(9):1285-1300
Cilia are antenna-like organelles found on the surface of most cells. They transduce molecular signals and facilitate interactions between cells and their environment. Ciliary dysfunction has been shown to underlie a broad range of overlapping, clinically and genetically heterogeneous phenotypes, collectively termed ciliopathies. Literally, all organs can be affected. Frequent cilia-related manifestations are (poly)cystic kidney disease, retinal degeneration, situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and defects of the central and peripheral nervous system, occurring either isolated or as part of syndromes. Characterization of ciliopathies and the decisive role of primary cilia in signal transduction and cell division provides novel insights into tumorigenesis, mental retardation, and other common causes of morbidity and mortality, including diabetes mellitus and obesity. New technologies (“Next generation sequencing/NGS”) have considerably improved genetic research and diagnostics by allowing simultaneous investigation of all disease genes at reduced costs and lower turn-around times. This is undoubtedly a result of the dynamic development in the field of human genetics and deserves increased attention in genetic counselling and the management of affected families. 相似文献
2.
Sieswerda-Hoogendoorn T Boos S Spivack B Bilo RA van Rijn RR 《European journal of pediatrics》2012,171(4):617-623
Abusive head trauma (AHT) is a relatively common cause of neurotrauma in young children. Radiology plays an important role
in establishing a diagnosis and assessing a prognosis. Computed tomography (CT), followed by magnetic resonance imaging (MRI)
including diffusion-weighted imaging (DWI), is the best tool for neuroimaging. There is no evidence-based approach for the
follow-up of AHT; both repeat CT and MRI are currently used but literature is not conclusive. A full skeletal survey according
to international guidelines should always be performed to obtain information on possible underlying bone diseases or injuries
suspicious for child abuse. Cranial ultrasonography is not indicated as a diagnostic modality for the evaluation of AHT. If
there is a suspicion of AHT, this should be communicated with the clinicians immediately in order to arrange protective measures
as long as AHT is part of the differential diagnosis. Conclusion: The final diagnosis of AHT can never be based on radiological findings only; this should always be made in a multidisciplinary
team assessment where all clinical and psychosocial information is combined and judged by a group of experts in the field. 相似文献
3.
4.
Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non-oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit-specific ROP risk profile and, consequently, may vary between different European regions. Conclusion: Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific. 相似文献
5.
Fractures are reported to be the second most common findings in child abuse, after skin lesions such as bruises and contusions.
This makes careful interpretation of childhood fractures in relation to the provided clinical history important. In this literature
review, we address imaging techniques and the prevailing protocols as well as fractures, frequently seen in child abuse, and
the differential diagnosis of these fractures. The use of a standardised protocol in radiological imaging is stressed, as
adherence to the international guidelines has been consistently poor. As fractures are a relatively common finding in childhood
and interpretation is sometimes difficult, involvement of a paediatric radiologist is important if not essential. Adherence
to international guidelines necessitates review by experts and is therefore mandatory. As in all clinical differential diagnoses,
liaison between paediatricians and paediatric radiologists in order to obtain additional clinical information or even better
having joint review of radiological studies will improve diagnostic accuracy. It is fundamental to keep in mind that the diagnosis
of child abuse can never be solely based on radiological imaging but always on a combination of clinical, investigative and
social findings. The quality and interpretation, preferably by a paediatric radiologist, of radiographs is essential in reaching
a correct diagnosis in cases of suspected child abuse. 相似文献
6.
Although cure rates for children with cancer are approximately 70%, improvements in cure rates have slowed in the past decade,
likely due to our inability to further improve outcome using currently available drugs. Novel drug approaches are needed for
children with difficult-to-treat malignancies, such as stage IV neuroblastoma, sarcomas, brain tumors, and relapsed leukemia.
Several novel agents show promise for improving outcome in patients with either high risk or recurrent disease. For leukemia,
inhibitors of cell cycle progression, such as clofarabine and nelarabine, have shown great promise in their ability to increase
treatment efficacy in high-risk disease. Targeted agents such as tyrosine kinase inhibitors, DNA binding compounds (trabectedin),
and monoclonal antibodies (GD2 inhibitors for neuroblastoma and anti-CD22 antibodies for pre-B acute lymphocytic leukemia
(ALL)) also show promise for future treatment. Extensive reviews of each of these agents are presented elsewhere; this article
provides an overview of molecular agents at different stages of FDA/EMA approval; those that are currently approved for use
in children, currently approved for use in adults, as well as those that show promise in early clinical trial testing, or
are supported by strong preclinical data. 相似文献
7.
The neutrophilic granulocyte (neutrophil) is the most important cellular component of the innate immune system. A total absence
of neutrophils or a significant decrease in their number leads to severe immunodeficiency. A mature neutrophil, released from
the bone marrow, should be able to migrate from the blood towards the tissues, following a chemotactic gradient to a pathogen.
In order to be neutralized, this pathogen has to be recognized, phagocytosed, and destroyed by lytic enzymes contained in
the neutrophil's granules and reactive oxygen species formed by the enzyme complex NADPH oxidase. Rare genetic defects leading
to the loss of each one of these biological properties of the neutrophil have been described and are associated with immunodeficiency.
This review provides a summary of the normal development and biological functions of neutrophils and describes the diseases
caused by defects in neutrophil number and function. 相似文献
8.
Retinal dystrophies are inherited disorders of photoreceptor and retinal pigment epithelial function that may result in severe
visual impairment. Advances in molecular genetics have helped identify many of the gene defects responsible, and progress
in gene transfer technology has enabled therapeutic strategies to be developed and applied. The first human clinical trials
of gene therapy for RPE65 associated retinal dystrophy have shown promising initial results and have helped prepare the way for further trials of gene
therapy for inherited retinal disorders. The results of these trials will provide further insight into the safety and efficacy
of gene therapy for a range of currently untreatable and debilitating eye disorders. 相似文献
9.
In the recent past, hereditary podocytopathies have increasingly been recognized to be involved in the development of steroid-resistant nephrotic syndrome (SRNS). Mutations in podocyte genes substantially alter the development and structural architecture of the podocyte including its interdigitating foot processes. These constitute the basis of the slit diaphragm which is an essential part of the glomerular filtration barrier. Depending on the affected protein, the clinical course is variable with respect to onset and severity of the disease as well as treatment options. In general, hereditary podocytopathies are associated with a poorer renal outcome than the non-genetic variants. In addition, they require a different approach with respect to the applied therapeutic strategies as most patients do not respond to immunosuppressive agents. Therefore, genetic testing of podocyte genes should be considered as a routine diagnostic tool for patients with SRNS because the identification of a genetic origin has a direct implication on clinical course, renal outcome, and genetic counseling. In this educational paper, we will give an overview over the podocyte genes identified so far to be involved into the pathophysiology of hereditary podocytopathies. 相似文献
10.
Sieswerda-Hoogendoorn T Boos S Spivack B Bilo RA van Rijn RR 《European journal of pediatrics》2012,171(3):415-423
Abusive Head Trauma (AHT) refers to the combination of findings formerly described as shaken baby syndrome. Although these
findings can be caused by shaking, it has become clear that in many cases there may have been impact trauma as well. Therefore
a less specific term has been adopted by the American Academy of Pediatrics. AHT is a relatively common cause of childhood
neurotrauma with an estimated incidence of 14–40 cases per 100,000 children under the age of 1 year. About 15–23% of these
children die within hours or days after the incident. Studies among AHT survivors demonstrate that approximately one-third
of the children are severely disabled, one-third of them are moderately disabled and one-third have no or only mild symptoms.
Other publications suggest that neurological problems can occur after a symptom-free interval and that half of these children
have IQs below the 10th percentile. Clinical findings are depending on the definitions used, but AHT should be considered
in all children with neurological signs and symptoms especially if no or only mild trauma is described. Subdural haematomas
are the most reported finding. The only feature that has been identified discriminating AHT from accidental injury is apnoea.
Conclusion: AHT should be approached with a structured approach, as in any other (potentially lethal) disease. The clinician can only
establish this diagnosis if he/she has knowledge of the signs and symptoms of AHT, risk factors, the differential diagnosis
and which additional investigations to perform, the more so since parents seldom will describe the true state of affairs spontaneously. 相似文献
11.
Ginsberg JP 《European journal of pediatrics》2011,170(6):703-708
Over the past several decades, pediatric oncologists have seen the growth in the number of patients surviving their cancer.
This is in large part due to the use of multimodal therapy including chemotherapy, surgery, and radiotherapy. As the number
of survivors of pediatric cancer continues to grow, however, we need to begin to focus on improving the quality of the lives
that are being saved. Unfortunately, many regimens used today to cure pediatric cancer patients are gonadotoxic. Therefore,
many of our survivors must contend with infertility. It is critical that pediatric oncologists consider the likelihood of
gonadotoxicity prior to beginning therapy in this patient population in order to counsel patients and their families properly
in order to potentially offer fertility preservation options. Conclusion: Infertility is a critical quality of life issue for pediatric cancer survivors and their families. Fertility preservation
techniques need to continue to be studied and developed in order to lessen the likelihood that future cancer survivors will
be infertile. This review outlines the risk for infertility, provides an assessment of the survivors reproductive functioning,
and summarizes the currently available methods of preserving fertility in pediatric cancer survivors. 相似文献
12.
Heritable connective tissue diseases comprise a heterogeneous group of multisystemic disorders that are characterized by significant morbidity and mortality. These disorders do not merely result from defects in the amount or structure of one of the components of the extracellular matrix, as the extracellular matrix also serves other functions, including sequestration of cytokines, such as transforming growth factor beta (TGFβ). Indeed, disturbed TGFβ signaling was demonstrated in several heritable connective tissue diseases, including syndromic forms such as Marfan or Loeys-Dietz syndrome and non-syndromic presentations of thoracic aortic aneurysm/dissection. Because of these findings, new therapeutic targets have been unveiled, leading to the initiation of large clinical trials with angiotensin II type 1 receptor antagonists that also have an inhibiting effect on TGFβ signaling. Here, we present an overview of the clinical characteristics, the molecular findings, and the therapeutic strategies for the currently known syndromic and non-syndromic forms of thoracic aortic aneurysm/dissection. 相似文献
13.
Improvements in our understanding of the genetic basis of human disease and increased utilization of genetic testing have
identified a variety of heritable disorders associated with the onset of benign or malignant neoplasms during childhood. In
many cases, the optimal management of affected children is dependent upon the early detection and treatment of tumors. Surveillance
strategies based on the natural history of these lesions are often complex, requiring clinical examinations and radiologic
and laboratory studies that evolve over a patient’s lifetime. A general pediatrician may be the first to suspect one of these
disorders in a patient, or may be faced with questions regarding genetic testing, cancer risk, and cancer screening. The pediatrician
may also coordinate and interpret the results of specific surveillance studies. In this review, we present the genetic etiology,
presentation, natural history, and surveillance recommendations for four disparate hereditary tumor predisposing syndromes,
including Beckwith–Wiedemann syndrome/idiopathic hemihyperplasia, von Hippel–Lindau disease, Li–Fraumeni syndrome, and rhabdoid
tumor/schwannomatosis. These examples are meant to offer the clinician practical recommendations as well as a framework upon
which to base the understanding and management of other conditions associated with an increased risk to develop tumors in
childhood. 相似文献
14.
Congenital cataract is the commonest worldwide cause of lifelong visual loss in children. Although congenital cataracts have
a diverse aetiology, in many children, a cause is not identified; however, autosomal dominant inheritance is commonly seen.
Early diagnosis either on the post-natal ward or in the community is important because appropriate intervention can result
in good levels of visual function. However, visual outcome is largely dependent on the timing of surgery when dense cataracts
are present. Good outcomes have been reported in children undergoing surgery before 6 weeks of age in children with unilateral
cataract and before 10 weeks of age in bilateral cases. Placement of an artificial intraocular lens implant after removal
of the cataract has become established practice in children over 2 years of age. There remains debate over the safety and
predictability of intraocular lens implantation in infants. Despite early surgery and aggressive optical rehabilitation, children
may still develop deprivation amblyopia, nystagmus, strabismus, and glaucoma. The diagnosis and management of congenital cataracts
has improved substantially over the past 30 years with a concurrent improvement in outcomes for affected children. Many aspects
of the pre-, intra-, and postoperative management of these patients continue to be refined, highlighting the need for good
quality data and prospective collaborative studies in this field. 相似文献
15.
Taylor DS 《European journal of pediatrics》2012,171(7):1007-1009
Retinal haemorrhages are an important component of the clinical effects of non-accidental head injuries which have significant visual morbidity. Their importance extends into the legal investigations of carers of children with subdural haemorrhages and encephalopathy who are suspected of having been non-accidentally injured. The vital precision in diagnosis relies not just on the presence of retinal haemorrhages but on the severity, extent, bilaterality and their location in the retina. Inadequate documentation of ophthalmological clinical findings and too short a follow-up to allow proper assessment of severity each give rise to difficulties for both expert witnesses and the courts. 相似文献
16.
The syndromic primary immunodeficiencies are disorders in which not only the immune system but also other organ systems are
affected. Other features most commonly involve the ectodermal, skeletal, nervous, and gastrointestinal systems. Key in identifying
syndromic immunodeficiencies is the awareness that increased susceptibility to infections or immune dysregulation in a patient
known to have other symptoms or special features may hint at an underlying genetic syndrome. Because the extraimmune clinical
features can be highly variable, it is more difficult establishing the correct diagnosis. Nevertheless, correct diagnosis
at an early age is important because of the possible treatment options. Therefore, diagnostic work-up is best performed in
a center with extensive expertise in this field, having immunologists and clinical geneticists, as well as adequate support
from a specialized laboratory at hand. This paper provides the general pediatrician with the main clinical features that are
crucial for the recognition of these syndromes. 相似文献
17.
Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence
of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical
presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable
immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background,
clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities. 相似文献
18.
Primary immunodeficiencies (PIDs) are characterized by an increased susceptibility to infections due to defects in one ore
more components of the immune system. Although most PIDs are relatively rare, they are more frequent than generally acknowledged. Early diagnosis and treatment
of PIDs save lives, prevent morbidity, and improve quality of life. This early diagnosis is the task of the pediatrician who
encounters the child for the first time: he/she should suspect potential PID in time and perform the appropriate diagnostic
tests. In this educational paper, the first in a series of five, we will describe the most common clinical presentations of
PIDs and offer guidelines for the diagnostic process, as well as a brief overview of therapeutic possibilities and prognosis. 相似文献
19.
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the
production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging
from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which
the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections,
PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis,
and treatment of the different PADs. 相似文献
20.
It is the pediatrician’s role to promote the child’s well-being and to help parents raise healthy, well-adjusted children.
Today’s pediatricians are confronted with a patient population in which there is a high prevalence of child abuse in its different
presentations (physical, sexual, and psychological abuse and/or neglect). The immediate and long-term consequences of child
abuse often are lifelong and even life-threatening in its most dramatic presentation. Unfortunately, detection of child abuse
remains a difficult challenge for many physicians but also for the “well-trained” pediatrician, leaving many abused children
unreported. This paper addresses the important role pediatricians can play in the detection, diagnosis, and prevention of
child maltreatment. 相似文献