Genetic variants in IRF6 and the risk of facial clefts: single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway

Mutations in the gene encoding interferon regulatory factor 6 (IRF6) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996-2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the 'a'-allele at rs4844880 had an increased risk of having a child with CL/P (RR=1.85, 95% confidence interval: 1.04-3.25; P=0.036). An RR of 0.38 (95% confidence interval: 0.16-0.92; P=0.031) was obtained when the child carried a single-dose of the 'a'-allele at rs2235371 (the p.V274I polymorphism). The P-value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test (P=0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population.     

Maternal periconceptional alcohol consumption and risk of orofacial clefts

Using data from the National Birth Defects Prevention Study, the authors investigated the association between maternal reports of periconceptional alcohol consumption and clefting. Cases with a cleft lip, cleft palate, or both and unaffected controls delivered from 1997 through 2002 were ascertained. Interview reports of alcohol consumption were obtained from 1,749 (75.1%) case and 4,094 (68.2%) control mothers. Adjusted odds ratios and 95% confidence intervals were calculated to assess associations. Compared with odds ratios for mothers with no reported consumption, those for mothers who consumed alcohol tended to be near to (cleft lip, cleft lip with cleft palate) or to exceed (cleft palate) unity. The odds ratios associated with binge drinking were elevated but did not demonstrate significantly increased risk for any phenotype; however, the odds ratios differed by the type of alcohol consumed, particularly for cleft palate (distilled spirits > wine > beer). These odds ratios were further increased among mothers with no reported folic acid intake. Although these findings suggest that the association between alcohol consumption and clefting might be most influenced by the type of beverage consumed and folic acid intake, they are preliminary and might reflect chance associations. Such findings need exploration in additional, large studies.     

Maternal cigarette smoking and oral clefts: a population-based study.

Analyses of 1984 data from the Maryland Birth Defects Reporting and Information System indicate that mothers of infants with oral clefts (cleft lip with or without cleft palate; and cleft palate) smoked more during pregnancy than mothers of infants with other defects (odds ratio OR of 2.56 and 2.39, respectively). There was a dose-response relation between the daily amount smoked and the risk of clefting. Adjustment for available confounding variables did not account for the association between smoking and oral clefts.     

Cleft lip and palate versus cleft lip only: are they distinct defects?

Cleft lip defects are usually regarded as a single entity, with the assumption that an accompanying cleft palate represents the more severe form. The authors linked data from the Medical Birth Registry of Norway with medical records from two centralized centers to provide a population-based data set. They assessed the distribution of cleft lip only and cleft lip with cleft palate by covariate. Among 1.8 million Norwegian livebirths between 1967 and 1998, there were 1,572 cases of cleft lip with cleft palate and 1,122 cases with cleft lip only. Seventeen percent of those with cleft lip and palate had another defect compared with 9% of those with cleft lip only. For boys, the risk was greater for cleft lip and palate than for cleft lip only (odds ratio=2.4 vs. 1.8, p<0.001 for difference). The risk of cleft lip only, but not of cleft lip and palate, was increased for twins (odds ratio=1.6 vs. 1.1, p=0.11) and infants whose parents were first cousins (odds ratio=2.7 vs. 0.7, p=0.07). Although cleft lip with cleft palate may simply represent a more severe form of the defect, epidemiologic assessments of cleft lip should, when possible, include separate analyses of these two groups.     

Parent's age and the risk of oral clefts

BACKGROUND: Some malformations are clearly associated with older maternal age, but the effect of older age of the father is less certain. The aim of this study is to determine the degree to which maternal age and paternal age independently influence the risk of having a child with oral clefts. METHODS: Among the 1,489,014 live births in Denmark during 1973-1996, there were 1920 children with nonsyndromic cleft lip with or without cleft palate and 956 children with nonsyndromic cleft palate. We used logistic regression to assess the impact of parental age on the occurrence of cleft lip with or without cleft palate and cleft palate. Interaction between mother's and father's age was included in the analysis. RESULTS: Separate analyses of mother's and father's age showed that older age was associated with increased risk of both cleft lip with or without cleft palate and cleft palate only. In a joint analysis, both maternal and paternal ages were associated with the risk of cleft lip with or without cleft palate, but the contribution of each was dependent on the age of the other parent. In the analysis of cleft palate only, the effect of maternal age disappeared, leaving only paternal age as a risk factor. CONCLUSION: Both high maternal age and high paternal age were associated with cleft lip with or without cleft palate. Higher paternal age but not maternal age increased the risk of cleft palate only.     

Social Workers as Transition Brokers: Facilitating the Transition From Pediatric to Adult Medical Care

Transition from pediatric to adult medical care and the significant psychosocial considerations impacting this developmental process are a primary focus in health care today. Social workers are often the informal brokers of this complex and nuanced process and are uniquely trained to complete biopsychosocial assessments to understand the needs of patients and families and address psychosocial factors. Their extensive knowledge of resources and systems, along with their sophisticated understanding of the relationship issues, family dynamics, cultural implications, and basic person-in-context approach allow for unique collaboration with the health care team, family, and community supports to develop successful transition plans and programs.     

贫困地区出生缺陷患者家庭的负担分析

[目的]分析贫困地区出生缺陷经济负担及其特点。[方法]采用结构式访谈的方法,选择来自贫困地区的唇腭裂患者8例、先天性心脏病患者9例。[结果]单纯唇裂或腭裂的患者平均经济负担为4887元,直接医疗负担占的比重51%,但变异系数是最小的,而其他类别负担的变异系数相对较大;唇裂合并腭裂的患者平均经济负担是10021.7元,其中直接医疗负担所占比重近半;先心病患者平均经济负担为2.65万元,其中直接医疗负担占到94.8%,直接非医疗负担和间接负担的比重很低但变异程度很大。而出生缺陷对患者家庭的精神负担也是沉重的。[结论]在贫困地区,就诊的出生缺陷患者对家庭负担特点是直接负担重、间接负担轻、无形负担重,但直接非医疗负担和间接负担的变异系数要远远大于直接医疗负担,而精神负担是难以量化但却不容忽视的隐性负担。     

Implementation of standardized medical photography for cleft lip and palate audit

Much has been published relating to the treatment and surgical outcome of cleft lip and palate disorders. Clinical audit is one of the most important tools for assessing the quality of care provided, with medical photography an invaluable component of this process. The Clinical Standards Advisory Group Report 1998 recommended that cleft lip and palate patients should be audited when 0 (under 1 year of age), and then at the ages of 5, 10, 15 and 20 years. For both audit and research purposes, medical photographs need to be accurate and of a consistently high standard. This paper describes the development of a standardized photographic protocol for cleft patients of audit age, to the benefit of both the multidisciplinary team and the patients.     

Parents' emotional and social experiences of caring for a child through cleft treatment

Little is known about the experiences of parents caring for a child through long-term treatment for cleft lip and/or cleft palate. We conducted in-depth interviews with 35 parents with children between the ages of 20 weeks and 21 years to explore experiences across the treatment program. We analyzed the data using a constructivist grounded theory approach and present in detail in this article one subcategory from the analysis: managing emotions. Throughout childhood and adolescence, parents experienced conflicting emotions about their child's impairment, uncertainty about cleft treatment, and stigmatizing attitudes. Although parents attempted to manage emotional tensions by pursuing cleft treatments, the interventions could themselves be a source of conflict for them. We suggest that routine assessment of parents' emotional and social well-being should be included in cleft treatment programs, and access to psychosocial support made available.     

766 cases of oral cleft in Italy

Epidemiological and genetic variables for oral clefts were analysed for the years 1981–1989 in a case-control study of congenital malformations in the Emilia Romagna, Veneto, and Friuli regions, and in the Trento and Bolzano hospitals. Birth prevalence for all cases of cleft lip with or without cleft palate (CL(P)) was 8.2 per 10,000 births, and that for cleft palate only (CP) was 6.1 per 10,000. Coexisting abnormalities were found in 23% of CL(P) cases and in 43% of CP. No clusters in time or space were detected. For isolated clefts, a predominance of males among CL(P) and of females among CP was found; epilepsy was the only maternal risk factor correlated with clefts, and an association between clefting and consanguinity was found. Empirical recurrence risks were calculated in both isolated CL(P) and CP.     

Epidemiological aspects of cleft lip and palate in Iran

Orofacial clefts, including cleft lip with or without cleft palate (CL (P)), are common congenital malformations, second only to clubfoot in frequency of occurrence. The epidemiology and genetics of this disorder have been studied extensively in various countries by several investigators. The objective of this study is to assess the epidemiology and some genetic aspects of orofacial clefting at Imam Khomeini Hospital in Tehran. This study was a 7-year case series (retrospective) study from 1999 to 2006. The setting for the study was Imam Khomeini Hospital in Tehran, and the participants were all consecutive surgical cases with orofacial clefts referred to this hospital. One hundred and 77 cases of cleft lip and/or cleft palate were recorded during these 7 years. Seventy four of them (41.8%) were female and 103(58.2%) were male (M/F Ratio=1.39). Of all patients, 40 persons (22.6%) had isolated CP, 45 (25.4%) had cleft lip without cleft palate, and 92 (52%) had cleft lip with cleft palate (CL+P). Their M/F ratios were 1.66, 0.6 and 1.96 respectively. Of all CL (P) probands, 41 patients (29.9%) were bilaterally affected. In unilateral cases, the left side was affected nearly twice as frequently as the right side. Among the patients, 23 cases (13%) had other malformations; most commonly head and face abnormalities and then congenital heart disease. Fifty-four patients (30.5%) had consanguine parents; 33 (18.6%) were first cousins, 7 (4%) were second cousins, and 14 (7.9%) were distant relatives. There was a positive family history for cleft syndrome in 23 cases; most commonly CL-P. Our study reveals that the epidemiologic aspects of oral clefts in Iran are very similar to other Caucasian populations. It also suggests that a routine screening such as echocardiography and ruling out skeletal, hearing and visual problems may be necessary in cleft patients especially in children. It seems that genetic counseling and karyotyping can be very useful in patients with multiple malformations.     

河北省0～6岁儿童唇腭裂发生情况及因素分析

目的:探讨唇腭裂的发生和干预措施。方法:利用2003～2008年河北省0～6岁儿童出生缺陷调查资料进行回顾性分析。结果:2003～2008年河北省0～6岁唇腭裂患儿2 529例,发病率为5.70/万;河北省唇腭裂发生呈逐年增加趋势,2003年与2008年唇腭裂发病率与6年平均发病率比较差异具有统计学意义(P<0.01);在河北省11个区市中以邯郸市发病率最高,为9.13/万,与6年平均发病率比较差异具有统计学意义(P<0.01);男孩发病率高于女孩,男女性别比为1.81:1,多胞胎发病率高于单胎,乡村发病高于城镇,山区高于平原;河北省0～6岁唇腭裂发生遗传因素占5.42%,母亲因素占33.93%,父亲因素占4.71%;有55.08%接受孕前优生健康检查,74.77%接受孕期保健;5.10%的唇腭裂儿童接受矫治手术。结论:河北省唇腭裂发病率仍处于较高水平,且呈逐年增加趋势。应采取全方位综合预防干预措施,重视孕前优生健康检查,加强孕期保健和做好新生儿筛查,并及时、适时地为出生缺陷患儿进行矫治,真正提高人口素质和生活质量。     

1988—1992年中国非综合征性唇腭裂发生率的动态变化

目的：了解我国1988－1992年非综合征性唇腭裂发生率的动态变化趋势及流行病学特征。方法：在1988－1992年期间,采用以医院为单位的整群抽样方法,对全国500多所医院孕28周至产后7天的4349例非综合征性唇腭裂病例进行回顾性分析。结果：我国5年非综合征性唇腭裂发生率无显著性差异,城乡发生率也无显著性差异。男性发生率为14．9／万,女性发生率为11．7/万,差异有显著性,非综合征性唇腭裂的性别比为1．3：1。三类非综合征性唇腭裂各自的发生率为：唇裂合并腭裂：7．8／万,单纯性唇裂：3．8／万,单纯性腭裂：1．8/万。结论：我国非综合征性唇腭裂发生率无变化趋势,城乡无差异。男性高于女性,唇裂合并腭裂为最常见类型。     

胎儿唇腭裂产前诊断及预后研究现状

唇腭裂是最常见的颜面部畸形,对于该病的病因迄今尚未阐明,目前多认为该病是由于遗传、环境因素共同作用所致。中孕期通过超声、MRI等辅助检查方法可诊断胎儿唇腭裂。部分胎儿唇腭裂合并其他畸形,部分存在基因、染色体异常,影响患儿出生后生存质量及预后等,因此产前对胎儿唇腭裂的明确诊断至关重要。胎儿唇腭裂宫内手术治疗目前尚处于研究阶段,非综合征性唇腭裂(NSCL/P)患儿于婴幼儿期进行手术治疗后,多数可以康复。笔者拟就胎儿唇腭裂产前诊断及预后研究现状进行阐述,以提高临床对该病的诊治水平。     

A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes—cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a “cleft map” of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.     

Community-bases Team Approach to the Management of Children with Cleft Palate

The child born with a cleft palate may have many associated problems in feeding, respiration, dentition, hearing, speech, language, and intellectual development as well as in psychosocial development If the cleft is associated with a specific craniofacial syndrome, other physical problems may be present such as cardiac, kidney, digital, and visual involvement The need for an extensive treatment program can extend from birth through adulthood Important to the successful habilitation of these children is the early involvement of a multitude of specialists working together with the family in a team approach The primary task of the team is to make decisions concerning timing and sequence of intervention for each individual patient Several models for the delivery of health care services to the patient with a cleft palate are now in use A community-based team model will be described in this article as a unique approach to the management of this population and as one that may be implemented in a cost-effective manner in communities where cleft palate teams presently do not exist.     

Parental experiences of cleft lip and palate services

In 1995 a cleft liaison service was developed in a health and social care trust which comprises primary and secondary care. The service team includes hospital and community midwives, health visitors and a consultant orthodontist who had a particular interest, and experience in the care of children born with a cleft and often this work was in addition to their existing roles. Anecdotal evidence indicated that the service was of great help to parents but it had never been formally evaluated. Therefore this evaluation was designed to explore the needs and views of parents who had a baby or child with a cleft of the lip and or palate, using a qualitative, cross sectional approach. Following 20 parents interviews responses were recorded, transcribed and a content analysis completed. Three main themes emerged relating to the parents' emotional experiences, their need for information and their experience of caring for a child with a cleft. This study has provided insight into the service delivered by the team and reiterates the need for retaining, maintaining and expanding this specialist service to other localities. Updating midwifery and health visiting staff in terms of knowledge and expertise was implicit to provide a responsive service to meet the needs of the child and family.     

Psychosocial standards of care for children with cancer and their families: A national survey of pediatric oncology social workers

ABSTRACT

In 2015, an interdisciplinary group of psychosocial experts developed The Standards of Psychosocial Care for Children with Cancer and Their Families. This paper presents data from a national survey of pediatric oncology social workers and their experiences in delivering psychosocial care to children and families. In total, 107 social workers from 81 cancer institutions participated in a 25-item online survey that mirrored the 15 Standards for Psychosocial Care. Both closed and open-ended questions were included.

Social work participants reported that psychosocial support is being provided at most cancer centers surveyed, primarily by social workers and child life specialists, addressing adaptation to the cancer diagnosis, treatment, and transitions into survivorship or end-of-life care and bereavement. While social workers reported offering comprehensive services throughout the cancer trajectory, many of the 2015 Standards are not being systematically implemented. Areas for improvement include funding for psychosocial support staff and programs, incorporation of standardized assessment measures, assessment for financial burden throughout treatment and beyond, consistent access to psychology and psychiatry, integrated care for parents and siblings, and more inclusion of palliative care services from time of diagnosis.     

总唇裂发生率变化趋势分析

目的:了解贵州省1996~2003年总唇裂的流行病学特征及发生率的动态变化趋势。方法:采用以医院为单位的整群抽样方法,对贵州省17所医院孕28周至产后7天的围产儿及191例总唇裂病例进行回顾性分析。结果:总唇裂发生率为20.79/万,其中单纯性唇裂为6.64/万,唇裂合并腭裂为14.15/万,单纯性唇裂有升高趋势。城乡总唇裂的发生率(20.23/万、24.41/万)无明显差异;男性发生率为25.36/万,女性为15.70/万,性别比为1.81∶1。不同年龄组产妇间唇裂合并腭裂的发生率有显著性差异,并随产妇年龄增加有升高趋势。结论:1996~2003年贵州省总唇裂发生率无变化,城乡无差异,男性易感性大于女性;唇裂合并腭裂较常见,且产妇年龄对其有影响。