22q13 deletion syndrome: an update and review for the primary pediatrician

Recent advances in genetic testing can help to provide a specific diagnosis to children born with syndromes that result in congenital anomalies and developmental delay. One such emerging condition is the 22q13 deletion syndrome. With the introduction of subtelomeric fluorescence-in-situ hybridization (FISH) analysis, the 22q13 deletion has become recognized as a relatively widespread and underdiagnosed cause of mental retardation. Primary-care physicians play an important role in the care of children with 22q13 deletion syndrome, from suspecting the diagnosis in a developmentally delayed child through the medical, developmental, and behavioral aspects of their care. Furthermore, they serve as a valuable source of support and advocacy for the family and a resource for other care providers. The remainder of this article addresses the current state of knowledge regarding 22q13 deletion syndrome and offers the primary-care physician a framework in which to provide care and information.     

Pediatric urine testing.

Today, urinalysis is one of the most common clinical tests ordered for adult and pediatric patients. Because urine specimens are usually readily available and are obtained noninvasively, the urine testing is well suited for children. This article discusses the most common urine tests performed in children for screening purposes and also less common tests for diagnosis of specific disorders. Special considerations regarding urine specimen collection in children are discussed. Some simple tests that are underused by clinicians are mentioned, as are some exciting new molecular applications of urine testing.     

智力障碍儿童的亚端粒拷贝数变异检测

目的应用多重连接探针扩增技术(MLPA)检测亚端粒拷贝数变异,探讨遗传性智力障碍(ID)的发病机制。方法收集68例G-显带染色体核型分析结果正常的ID患儿,通过MLPA P036筛查亚端粒拷贝数变异。结果 68例患儿中检出亚端粒拷贝数异常者7例(10%),均为缺失突变,其中1例患儿涉及2个亚端粒的缺失变异,另1例患儿涉及4个亚端粒的缺失变异。结论亚端粒拷贝数变异是遗传性ID的重要病因;MLPA可作为研究遗传性ID患儿发病机制的经济、有效的方法。     

Rapid viral testing in the evaluation of the febrile infant and child

PURPOSE OF REVIEW: This review focuses on rapid viral testing in the febrile infant and child. Recent literature is reviewed regarding physician decision making, antibiotic use, ancillary testing use, and rate of serious bacterial infections concurrent with viral disease. RECENT FINDINGS: Two recent studies detail the use of rapid testing of influenza. The impact on the use of ancillary testing and antibiotic prescribing practices based on the knowledge provided by rapid viral testing has been evaluated. Physician awareness of a rapid diagnosis of influenza significantly reduced the number of laboratory tests and radiographs ordered and their associated charges, decreased antibiotic use, increased antiviral use, and decreased length of time to discharge. The rate of serious bacterial infections coexisting with influenza illness has also been studied. Researchers concluded that the prevalence of serious bacterial infections is lower in febrile children with influenza A infection. Another two studies evaluated respiratory syncytial virus-positive febrile infants and their risk of serious bacterial infection. Both studies independently noted that febrile infants with respiratory syncytial virus infections are at significantly lower risk of serious bacterial infection than febrile infants without respiratory syncytial virus infection. The rate of urinary tract infections remained significant in febrile respiratory syncytial virus-positive infants, however. SUMMARY: Various studies have documented the impact of rapid viral testing in the evaluation and management of febrile infants and children. There is insufficient evidence to change current clinical practice algorithms for young febrile infants and children. Continued research will affect future guidelines and algorithms in the management of febrile infants and children.     

Practitioner review: Psychopharmacology in children and adolescents with mental retardation

BACKGROUND: The use of psychotropic medication to treat children and adults with mental retardation (MR) has a long and extensive history. There are no identified medications to address specific cognitive deficits among persons with MR. Instead, psychotropic medications are used to treat specific behavioral symptoms and/or psychiatric syndromes. The purpose of this review is to provide an overview of the recent literature regarding the use of psychotropic medications in this population, focusing primarily on children and adolescents. METHODS: The paper is divided into five general drug categories: psychostimulants, antipsychotics, antidepressants, mood stabilizers, and other drugs. Each section offers an overview of the research supporting the use of that class of medications in children and adolescents with MR as well as cautions regarding potential side effects. Finally, specific clinical recommendations are offered. RESULTS: The majority of studies in MR tend to be open trials, case reports, or controlled studies with small samples. The available data suggests that persons with MR respond to various psychotropic medications in ways similar to the typically developing population. However, rates of response tend to be poorer and the occurrence of side effects tends to be more frequent. CONCLUSIONS: The use of psychotropic medications in children and adolescents with MR requires even greater monitoring and the use of lower doses and slower dosage increases than in the general population.     

不明原因智力障碍/脑发育迟缓患儿染色体亚端粒重组突变的检测

目的联合应用多重连接依赖的探针扩增法和荧光原位杂交法检测染色体亚端粒重组,进行不明原因智力障碍／脑发育迟缓（mental retardation／developmental delay,MR／DD）的病因学研究。方法人选病例必须满足：①中一重度MR／DD;②无明确围产期异常病史;③无明确生后中毒、缺氧、中枢神经系统感染及头颅外伤等病史;④常规核型分析显示正常;⑤头颅影像及尿有机酸、氨基酸分析未提示典型遗传代谢性疾病或神经变性病;⑥男性患儿FMR1基因检测未提示脆性X综合征。并至少符合以下条件之一：①MR家族史阳性;②反复流产或围产期死亡家族史阳性;③体格发育异常;④面部畸形;⑤非面部畸形或发育异常。联合应用多重连接依赖的探针扩增法过筛和荧光原位杂交技术验证对患儿及父母标本进行染色体亚端粒重组检测。结果人组39例中发现4例阳性病例,重组分别为：①新发der（2）t（2;4）（pter;pter）,文献未见报道;②新发8pter缺失,国外曾有报道,但临床表型不同;③新发15q11．2缺失,属中间重组,结合患儿临床表型,Angelman综合征可能性大;④新发11qter缺失,文献未见报道。结论首次报道2种新重组,其新发出现提示致病性可能性大;染色体亚端粒重组是遗传性MR／DD的重要病因,临床表型差异大,对原因不明的常规染色体检查无异常的MR／DD患者均应进行检测,联合应用多重连接依赖的探针扩增法和荧光原位杂交法是相对经济的确诊手段。     

Early prediction of the need for hospitalization in children with acute asthma

We studied 133 asthmatic children in the emergency room who were aged 4 to 17 years and who were not receiving ongoing training in pulmonary function testing, to determine whether spirometry correlated with the outcome of the emergency treatment of the acute attack and with relapse during the next four days. A clinical score derived from the physical exam was obtained at the time of spirometry. Patients were hospitalized or discharged home based solely on their clinical response to therapy. The pediatrician making that decision was blinded to the results of the spirometry. The initial pretreatment clinical score or spirometry alone identified the majority of patients hospitalized, but each falsely identified many discharged patients who did not relapse, 20 percent and 15 percent, respectively. Predictive criteria for hospitalization, combining spirometry with a careful clinical evaluation prior to the start of emergency treatment, substantially reduced the number of falsely identified patients. With use of the predictive criteria, the majority of children admitted to the hospital would have been identified hours before that decision was made on clinical grounds alone (5.5 +/- 0.7 hrs). This study suggests a role for spirometry as an adjunct to clinical evaluation in the early identification of the need for hospitalization of acutely ill asthmatic children.     

Genetic testing in children

Increasing availability of DNA based tests in clinical practice has lead to widespread debate on the ethical issues involved. The wider usage of these tests in children has raised many questions regarding the ethics, validity of the request and its effects on child’s psychosocial well-being. Though there have been much discussion with many studies attempting to address the issue, there is no consensus. Formulation of guidelines has been hampered by the diversity of tests available for varied indications and lack of research studying the effects of testing in children over a time. Some tests have valid indications with proven benefits over harms while others have less clear justification. We attempt to address this issue with the intent to sensitize the caregivers regarding various aspects to be considered before offering any genetic tests in children.     

Clinical manifestation of chromosome 2 long arm terminal deletion--presentation of four cases

Terminal deletion of the long arm of chromosome 2 belongs to the most common structural aberrations of subtelomeric chromosomal regions. Clinical manifestations of this syndrome comprise: global psychomotor delay, moderate to severe mental retardation with specific facial dysmorphism. In some cases a phenotype similar to Albright's hereditary osteodystrophy (AHO) may also be observed (short stature, obesity, brachydactyly). The paper covers the characteristics of clinical features in four cases of terminal deletions in 2q36.2, 2q37.1 and 2q37.3 identified in routine cytogenetic study and fluorescent in situ hybridization (FISH) technique. In one case the deletion of subtelomeric region of chromosome 2 (2q37.3) occurred as a result of reciprocal translocation between chromosomes 2 and 7. A comparison was made of clinical symptoms present in our patients with relevant data concerning other cases of 2q monosomy, described in specialized publications.     

Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections

From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency.     

正确理解和应用儿童肺功能检测

随着儿童肺功能检测技术的广泛开展,如何正确使用这一工具,更好地服务于临床,已成为儿科专业人员面临的问题。近年相关学会和机构在培训方面做了大量工作,但由于儿童肺功能检测技术方法与成人有所不同,儿童肺功能检测在临床应用中仍存在很多误区和争议,突出表现在项目的选择、检测的质控和报告的解读等方面。应进一步提高肺功能检测和报告解读的水平。     

Chronic Myeloid Leukemia (CML) in Children: Classical and Newer Therapeutic Approaches

Chronic myeloid leukemia (CML) represents a rare myeloproliferative disease among children where allogeneic stem cell transplantation (SCT) remains the curative gold standard. However, the impressive early cytogenetic and molecular responses achieved by tyrosine kinase inhibitors [TKIs (imatinib, nilotinib, and dasatinib)] as first-line or even sole treatment in adults, has led to their increasing use also among children. Due to limited data regarding long-term results of TKIs and especially those of second generation in pediatric cohorts, we would like to add clinical information in this rare series of patients by reporting on four children with CML over a 10-year period, focusing on TKIs, dose escalations and clinical responses.     

Comprehensive Versus Targeted Genetic Testing in Children with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that can be found in both children and adults and is associated with many causative mutations. In children who are not the index case of HCM in their families, current recommendations call only for targeted genetic testing for familial mutations. However, clinical experience suggests that de novo mutations are possible, as are mutations inherited from apparently an unaffected parent. A chart review was conducted of all patients who received HCM genetic testing at Johns Hopkins from 2004 to 2013. In total, 239 patient charts were analyzed for personal and familial genetic findings. Eighty-one patients with sarcomere gene mutations were identified, of which 66 had a clinical diagnosis of HCM. Importantly, eight patients had >1 pathogenic or likely pathogenic mutation, including six patients who were diagnosed with HCM as children (18 or younger). In this analysis, when a sarcomere mutation is identified in a family, the likelihood of a child with HCM having >1 mutation is 25 % (6/24), compared to 4.8 % (2/42) for adults. The large number of children with multiple mutations suggests that broad panel rather than targeted genetic testing should be considered in HCM presenting during childhood even if the child is not the index case.     

Diagnostic Outcome of Preoperative Coagulation Testing in Children

The value of routine coagulation testing instead of bleeding history alone in children, to predict bleeding risk prior to tonsillectomy and adenoidectomy has been questioned. Our objectives are to identify the causes of abnormal PT and/or aPTT in these patients, and to determine whether routine preoperative coagulation testing is effective in identifying children with a clinically significant coagulation abnormality prior to undergoing a procedure. In this study, data were extracted by chart review for 854 patients referred to the pediatric hematology service at Stony Brook University for the evaluation of an elevated PT and/or aPTT on preoperative testing. Seven hundred and ninety two of 854 reviewed charts (92.7%) contained sufficient data for analysis. On repeat testing, 393 (49.6%) had a laboratory abnormality identified. A potentially significant coagulation abnormality was identified in 32 of 792 patients (4%). For the remaining 760 patients, the most common diagnosis was a lupus anticoagulant (n = 98, 24.6%) or a “presumed” lupus anticoagulant (n = 166, 41.6%). A positive personal or family bleeding history was documented in 268 patients (268/792 = 33.8%). Of these patients, only 107 (39.9%) had an abnormality identified on further work-up. Seventeen of the 32 patients with clinically significant bleeding disorders identified were found to have a positive bleeding history (17/32 = 53.1%). Routine preoperative coagulation testing identifies only a small number of children at increased risk for surgical bleeding. However, a “positive” bleeding history identifies only 60% of children found to have a clinically significant coagulation abnormality. Routine preoperative coagulation testing may serve as a useful adjunct to clinical history.     

Leistungen des HAWIK-IV in der Intelligenzdiagnostik im Schulalter

The HAWIK-IV [Hamburg-Wechsler intelligence test for children IV, the German version of the WISC-IV (Wechsler Intelligence Scale for Children)], is a fundamental revision of its predecessor, HAWIK-III, characterized by the development of new sub-tests and the introduction of 4 indices for the interpretation of intelligence profiles. Thus, the question of its application in clinical and pedagogic settings arises. Individual strengths and weaknesses identified by means of discrepancy analyses are already able to provide information pointing to underlying disorders and comorbidities, as well as promotion approaches. The use of HAWIK-IV in pediatrics and pediatric psychiatry is discussed using children with dyslexia or attention deficit-hyperactivity syndrome (ADHD), as well as highly gifted children as examples.     

Cost-effective use of rapid diagnostic techniques in the treatment and prevention of viral respiratory infections

The most cost-effective current use of rapid respiratory virus diagnostics is through highly sensitive and specific molecular assays (mostly PCR-based) in the hospital setting or for chronically ill or immunocompromised outpatients. Specifically, this cost savings is the result of preventing hospitalization or decreasing length of hospitalization, decreasing unnecessary testing and procedures, directing specific therapy, and reducing unnecessary antibiotic use. Equally important is community surveillance by informing physicians rapidly what agents are in the community. Important ongoing issues regarding the cost-effective use of these assays include the cost of reagents or machinery, reimbursement for testing, the need for reliable commercial reagents, the need for open platforms that can respond to new "emerging" or "reemerging" agents, and the need for proficiency panels to share between laboratories. Rapid molecular diagnostic assays for the detection of respiratory viruses have moved into the mainstream of clinical testing. These assays already play important roles in select populations and clinical situations for critical patient management. In addition, there are numerous clinical scenarios where the use of these assays should have a positive cost/benefit ratio. Further work needs to be done to demonstrate this benefit to society. Further development of multiplex assays and decreasing the cost of testing will help improve the benefit of these assays to clinical care. Work is underway on large multiplex molecular assays with high sensitivity and specificity that will be able to be used in an outpatient setting both because of speed and low cost. The future holds great potential for physicians. who soon may be able to answer the age-old question, "Doc, what do I have?" with more than, "You probably have a virus."     

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician

Clinicians have been faced with much publicity and contradictory scientific evidence regarding a recently described condition termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). It has been proposed that children with PANDAS experience tics, obsessive-compulsive behavior, and perhaps other neuropsychiatric symptoms as an autoimmune response to streptococcal infection. We review current scientific information and conclude that PANDAS remains a yet-unproven hypothesis. Until more definitive scientific proof is forthcoming, there seems to be insufficient evidence to support 1) routine microbiologic or serologic testing for group A streptococcus in children who present with neuropsychiatric symptoms or 2) the clinical use of antibiotic or immune-modifying therapies in such patients. The optimum diagnostic and therapeutic approach awaits the results of additional research studies.     

Chronic lung disease of prematurity and respiratory outcome at eight years of age

AIM: The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. METHODS: Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. RESULTS: There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. CONCLUSION: Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.     

神经发育障碍患儿致病性拷贝数变异与临床表型分析

目的分析神经发育障碍患儿致病性拷贝数变异(pCNVs)的微缺失和微重复特征与患儿临床表型特点,明确神经发育障碍患儿遗传学病因。方法收集2017年1月至2019年11月安徽医科大学第一附属医院以全面性发育落后、智力障碍等神经发育障碍疾病就诊的患儿,应用全基因组拷贝数变异(CNVs)检测明确存在的pCNVs,总结分析患儿临床表型与pCNVs特点。结果31例患儿存在36处pCNVs,其中微缺失片段24个(占66.67%),微重复片段12个(占33.33%),片段大小320.00 kb^93.26 Mb,平均11.33Mb。pCNVs易发生在15号染色体,为9例患儿9处(占25.00%),其次是8号染色体,3例患儿5处(占13.89%),X染色体,3例患儿4处(占11.11%)。临床表现有运动发育落后的患儿30例(占96.77%),智力障碍22例(占70.97%),语言发育落后22例(占70.97%),伴畸形患儿11例(占35.48%),特殊面容11例(占35.48%)及癫痫8例(25.81%),且多种落后与多系统的异常同时存在。结论对不明原因的神经发育障碍患儿,可应用全基因组CNV方法进行检测,明确其遗传学病因;对pCNVs及所包含的功能基因的分析,可揭示神经发育障碍的遗传学发病机制。