RESUMO
Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high-volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U-shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U-shaped CP. The most common palatal morphology among those who died was an intact palate. U-shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.
Assuntos
Artrite/genética , Fenda Labial/genética , Fissura Palatina/genética , Doenças do Tecido Conjuntivo/genética , Perda Auditiva Neurossensorial/genética , Síndrome de Pierre Robin/genética , Descolamento Retiniano/genética , Artrite/diagnóstico por imagem , Artrite/mortalidade , Artrite/patologia , Criança , Pré-Escolar , Fenda Labial/diagnóstico por imagem , Fenda Labial/mortalidade , Fenda Labial/patologia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/mortalidade , Fissura Palatina/patologia , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Doenças do Tecido Conjuntivo/mortalidade , Doenças do Tecido Conjuntivo/patologia , Feminino , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/mortalidade , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Masculino , Síndrome de Pierre Robin/diagnóstico por imagem , Síndrome de Pierre Robin/mortalidade , Síndrome de Pierre Robin/patologia , Descolamento Retiniano/diagnóstico por imagem , Descolamento Retiniano/mortalidade , Descolamento Retiniano/patologia , Estudos RetrospectivosRESUMO
FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.
Assuntos
Anormalidades Múltiplas , Caseína Quinase I , Fissura Palatina , Exoftalmia , Proteínas da Matriz Extracelular , Variação Genética , Microcefalia , Osteosclerose , Fenótipo , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Caseína Quinase I/genética , Caseína Quinase I/metabolismo , Fissura Palatina/genética , Fissura Palatina/metabolismo , Fissura Palatina/mortalidade , Fissura Palatina/patologia , Exoftalmia/genética , Exoftalmia/metabolismo , Exoftalmia/mortalidade , Exoftalmia/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Microcefalia/genética , Microcefalia/metabolismo , Microcefalia/mortalidade , Microcefalia/patologia , Osteosclerose/genética , Osteosclerose/metabolismo , Osteosclerose/mortalidade , Osteosclerose/patologiaRESUMO
BACKGROUND: Only two population-based studies have reported survival beyond 15 years for individuals with orofacial clefts (OFC), and only for individuals with isolated OFC. Compared with the general population, long-term survival was similar for individuals with cleft lip only, and lower for individuals with cleft palate only. Results for those born with isolated cleft lip and cleft palate were inconsistent. METHODS: Using linked population-based health data, including a congenital anomaly register with active surveillance and diagnoses up to 6 years, we compared survival at 1, 5, and 20 years for infants born 1980 to 2010 with, and without OFC. RESULTS: Of the 8112 live born infants in the cohort, 186 died before 20 years; most (81%) died during infancy. Compared with infants without OFC, infants born with all types of isolated OFC ± additional minor anomalies had similar infant survival (around 99%), but we found lower survival for infants with all cleft types and an additional major anomaly (66-84%). From 1 to 5 years, only infants with cleft palate only and an additional major anomaly had lower survival (97%) compared with children without OFC (99.9%). From 5 to 20 years, children with all cleft types, with or without additional major anomalies had similar survival to children without OFC (98-100%). CONCLUSION: Parents with a child diagnosed with an OFC ± additional minor anomalies only can be reassured that the OFC does not influence survival rates in infancy, or long-term. Infant survival was lower only for children with OFC and additional major anomalies.
Assuntos
Anormalidades Múltiplas/mortalidade , Mortalidade da Criança/tendências , Fenda Labial/mortalidade , Fissura Palatina/mortalidade , Mortalidade Infantil/tendências , Anormalidades Múltiplas/epidemiologia , Criança , Pré-Escolar , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Austrália Ocidental/epidemiologiaRESUMO
Cleft palate only (CPO) is a common congenital malformation, and most patients are diagnosed within the first weeks after birth. Late diagnosis of the cleft palate (CP) could initially result in feeding and growth impairment, and subsequently speech and hearing problems later in life. The purpose of this study is to retrospectively investigate (1) at which age CPO is diagnosed and (2) how the presence of syndromes and other factors relate to the age at diagnosis. The mean age of all children at our centre with CPO included between 1997 and 2014 at diagnosis (n = 271) was 1 year and 4 months. In all, 24.8% (n = 67) was older than 12 months when diagnosed, and 37.3% (n = 101) of all children had been diagnosed >30 days. These findings remain valid when a cut-off point of 14 days is used (44.3% late). Moreover, the grade of the cleft was a determining factor for successful diagnosis; submucous clefts were detected much later on average (89.3% > 30 days; p = .000). Similar results were found using Kaplan-Meier survival analyses. CONCLUSION: CPO is often diagnosed late. Patients diagnosed ≤30 days after birth more often presented with an associated disorder. Early diagnoses became more frequent as the severity of the cleft increased (grades 1-4). Professionals should perform more thorough intra-oral investigations, including manual palpations and visual inspections of the palate; they should be made more aware of the frequent accompanying symptoms. WHAT IS KNOWN: The presence of cleft palate only (CPO) is known to negatively affect feeding, hearing, speech and (social) development. Submucous clefts are often underdiagnosed due to their difficulty to detect. As far as we know the literature shows that symptomatic submucous CPs are often diagnosed at an average age of 4.9 years. WHAT IS NEW: 37.3% respectively of all children with CPO were diagnosed relatively late (>30 days after birth), 24.8% was older than 12 months when diagnosed. Mean age of all children with CPO was 1 year and 4 months. We conclude that midwives and pediatricians should perform more through intra-oral investigations of all new-borns, including both a manual palpation, als well a visual inspection of the palate.
Assuntos
Fissura Palatina/diagnóstico , Fatores Etários , Fissura Palatina/mortalidade , Fissura Palatina/patologia , Parto Obstétrico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
Objectives : Resources for repair of cleft lip and palate may be lacking in low- and middle-income countries. The Smile Train is a registered charity that supports cleft repair in resource-poor settings. In the global health care challenge, it has been suggested that many babies born with cleft palates are not repaired. This study aims to determine whether any variation exists in the proportion of cleft lip and cleft palate repairs undertaken in low- and middle-income countries. Methods : Data were obtained from the Smile Train database of 352,191 consecutive cleft operations performed between 2008 and 2011 in low- to higher-middle-income countries. The ratio of cleft lip to palate repair was analyzed as a function of geographic region and by country income (gross national income). Results : A significant correlation exists between both the income of a country and its geographical region to the ratio of lip and palate repair procedures undertaken. Higher-income countries had a higher ratio of cleft palate repairs. Countries in sub-Saharan Africa have the lowest proportion of cleft palate repairs. Conclusion : This study emphasizes that many babies born with cleft palates in resource-poor regions do not have their palates repaired. This finding may be explained by an increased neonatal mortality in cleft palate babies. Furthermore, fewer isolated palatal clefts may present to an appropriate health care facility or there may be a reluctance to treat cleft palate due to concerns regarding higher perioperative risks or the lack of available surgical and anesthetic expertise.
Assuntos
Instituições de Caridade , Fissura Palatina/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Fissura Palatina/mortalidade , Bases de Dados Factuais , Países Desenvolvidos , Países em Desenvolvimento , Humanos , Lactente , Mortalidade Infantil , Recém-NascidoRESUMO
OBJECTIVE: The purpose of this study was to assess length of stay (LOS), complication rates, costs, and charges of cleft palate repair by various hospital types. We hypothesized that pediatric hospitals would have shorter LOS, fewer complications, and lower costs and charges. METHODS: Patients were identified by ICD-9-CM code for cleft palate repair (27.62) using databases from the Agency for Health Research and Quality Healthcare Cost and Utilization Project Kids' Inpatient Database from 1997, 2000, 2003, and 2006. Patient characteristics (age, race, gender, insurer, comorbidities) and facility resources (hospital beds, cleft palate surgery volume, nurse-to-bed ratio, pediatric intensive care unit [PICU], PICU intensivist, burn unit) were examined. Hospitals types included pediatric hospitals, general hospitals, and nonaccredited children's hospital. For each hospital type, mean LOS, extended LOS (LOS > 2), and complications were assessed. RESULTS: A total of 14,153 patients had cleft repair with a mean LOS of 2 days (SD, 0.04), mortality 0.01%, transfusion 0.3%, and complication <3%. Pediatric hospitals had fewer patients with extended hospital stays. Patients with an LOS >2 days were associated with fourfold higher complications. Comorbidities increased the relative rate of LOS >2 days by 90%. Pediatric hospitals had the highest comorbidities, yet 35% decreased the relative rate of LOS >2 days. Median total charges of $10,835 increased to $15,104 with LOS >2 days; median total costs of $4367 increased to $6148 with a LOS >2 days. CONCLUSION: Pediatric hospitals had higher comorbidities yet shorter LOS. Pediatric resources significantly decreased the relative rate of LOS >2 days. Median costs and charges increased by 41% with LOS >2 days. Further research is needed to understand additional aspects of pediatric hospitals associated with lower LOS.
Assuntos
Fissura Palatina/cirurgia , Preços Hospitalares/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Criança , Pré-Escolar , Fissura Palatina/mortalidade , Comorbidade , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/mortalidade , Estados Unidos/epidemiologiaRESUMO
Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient-gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity.
Assuntos
Ácido Fólico/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Morfogênese , Defeitos do Tubo Neural/metabolismo , Anencefalia/genética , Anencefalia/metabolismo , Anencefalia/fisiopatologia , Animais , Fenda Labial/genética , Fenda Labial/metabolismo , Fenda Labial/fisiopatologia , Fissura Palatina/complicações , Fissura Palatina/genética , Fissura Palatina/mortalidade , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Interação Gene-Ambiente , Humanos , Camundongos , Defeitos do Tubo Neural/fisiopatologia , GravidezRESUMO
Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene that is characterized by generalized osteosclerosis with periosteal new bone formation and distinctive craniofacial dysmorphism. We report on a child who is homozygous for a 487-kb deletion in 7p22.3 that contains FAM20C. Both parents were heterozygous for the deletion. Our patient had the common craniofacial features as well as, uncommon features such as protruding tongue, short stature, and hypoplastic distal phalanges. In addition, he had wormian bones and pyriform aperture stenosis, features that are usually under diagnosed. It is clear that Raine syndrome has a wide range of expression and may not be lethal in the neonatal period. Furthermore, Raine cases due to whole gene deletion do not seem to have a major difference in the phenotype over those caused by various mutations.
Assuntos
Anormalidades Múltiplas/genética , Fissura Palatina/genética , Exoftalmia/genética , Proteínas da Matriz Extracelular/genética , Microcefalia/genética , Osteosclerose/genética , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/fisiopatologia , Doenças do Desenvolvimento Ósseo/genética , Caseína Quinase I , Fissura Palatina/etiologia , Fissura Palatina/mortalidade , Fissura Palatina/fisiopatologia , Exoftalmia/etiologia , Exoftalmia/mortalidade , Exoftalmia/fisiopatologia , Deleção de Genes , Humanos , Recém-Nascido , Masculino , Microcefalia/etiologia , Microcefalia/mortalidade , Microcefalia/fisiopatologia , Mutação , Osteosclerose/complicações , Osteosclerose/etiologia , Osteosclerose/mortalidade , Osteosclerose/fisiopatologiaRESUMO
OBJECTIVE: To determine mortality rate and cause of death in infants born with orofacial clefts. METHODS: Retrospective case note review of all children with orofacial clefts within the East of England Cleft Network who have died. RESULTS: Between 2002 and 2010, of 638 children born with orofacial clefts, 23 died at a median age of 5 months (range, 1 day to 4 years). The overall mortality rate was 36 per 1000 cleft births. A total of 21 deaths were in the isolated cleft palate group, with a calculated death rate of 68.1 per 1000. One child each from the cleft lip and the cleft lip and palate groups died. Of the children who died, 21 (91%) had other structural abnormalities. Of these children, 19 (83%) died before their first birthday. The causes of death were mainly due to associated congenital anomalies (61%) and infection (17%). CONCLUSIONS: Children born with cleft palate have a 15-fold increase in mortality compared with the regional East of England infant mortality rate and at least a 10-fold increase when compared with other clefts. Pediatricians should be involved in the care of these complicated patients.
Assuntos
Fenda Labial/mortalidade , Fissura Palatina/mortalidade , Causas de Morte , Inglaterra/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
Reports of birth defects rates may focus on defects observed in the newborn period or include defects diagnosed at older ages. However, little information is available on the rates of additional anomalies detected after birth or on the ages at which such anomalies are diagnosed. The aims of this work were to describe the initial diagnoses of oral clefts, isolated or associated with other defects, in newborn infants ascertained in hospitals of the ECLAMC network, and diagnostic changes that occurred due to detection of additional defects during a 1-year follow-up period. Seven hundred ten liveborn infants with cleft lip only (CLO), cleft lip with cleft palate (CLP), or cleft palate (CP) were ascertained between 2003 and 2005. Prevalence estimates of isolated and associated (ASO) clefts, diagnoses in infants with associated clefts, and the percentage of isolated clefts that were reclassified as associated were established. Birth prevalence estimates (per 1,000) were as follows: Total: 1.7; CLP: 0.94 (ASO = 23.5%); CP: 0.46 (ASO = 42.3%); CLO: 0.28 (ASO = 7.6%). Initial diagnoses in infants with associated clefts included 38 infants with chromosomal abnormalities, 33 with non-chromosomal syndromes, 16 with malformation sequences, and 98 with multiple anomalies of unknown etiology. Seven percent of newborns initially classified as isolated were later reclassified as associated. Ten infants without associated defects or clinically suspected syndromes were diagnosed as syndromic only through laboratory findings or family history, illustrating the difference between the terms associated versus isolated, which refers to presence or absence of associated anomalies, and syndromic versus non-syndromic, which refers to etiology.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/epidemiologia , Fenda Labial/complicações , Fenda Labial/diagnóstico , Fenda Labial/epidemiologia , Anormalidades Múltiplas/genética , Fenda Labial/genética , Fenda Labial/mortalidade , Fissura Palatina/complicações , Fissura Palatina/diagnóstico , Fissura Palatina/epidemiologia , Fissura Palatina/mortalidade , Seguimentos , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Prevalência , América do Sul/epidemiologia , SíndromeRESUMO
BACKGROUND: Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America. METHODS: The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7th and 28th day of life. The primary outcomes were mortality between the 7th and 28th day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates. RESULTS: There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group. CONCLUSIONS: Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00097149.
Assuntos
Fenda Labial/mortalidade , Fissura Palatina/mortalidade , Hospitalização/estatística & dados numéricos , Cuidado do Lactente , Mortalidade Infantil , Fenda Labial/terapia , Fissura Palatina/terapia , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Pediatria/métodos , América do SulRESUMO
Cleft births surveillance is essential in healthcare and prevention planning. Data are needed in precision medicine to target upstream management for at-risk individuals. This study characterizes Singapore's population-based orofacial cleft topography by ethnicity and gender, and establishes the cleft cohort's infant mortality rate. Data, in the decade 2003 to 2012, were extracted by the National Birth Defects Registry. Trend testing by linear regression was at p < 0.05 significance level. Prevalence per 10,000 for population-based cleft live births was 16.72 with no significant upward trend (p = 0.317). Prevalence rates were 8.77 in the isolated cleft group, 7.04 in the non-isolated cleft group, and 0.91 in the syndromic cleft group. There was significant upward trend in infants with non-isolated clefts (p = 0.0287). There were no significant upward trends in infants with isolated clefts and syndromic clefts. Prevalence rates were sexually dimorphic and ethnic-specific: male 17.72; female 15.78; Chinese group 17.17; Malay group 16.92; Indian group 10.74; and mixed ethnic origins group 21.73. The overall infant mortality rate (IMR) was 4.8% in the cohort of 608 cleft births, which was more than double the population-based IMR of 2.1% in the same period. Infants with non-isolated and syndromic clefts accounted for 96.6% of the deaths.
Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Pré-Escolar , Fenda Labial/mortalidade , Fissura Palatina/mortalidade , Estudos de Coortes , Etnicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Anormalidades da Boca/epidemiologia , Prevalência , Sistema de Registros , Estudos Retrospectivos , Singapura/epidemiologiaRESUMO
Importance: Orofacial cleft (OFC) is one of the most common congenital malformations, with a wide variation in incidence worldwide. However, population-based studies on the incidence of OFC in North America are lacking. Objectives: To examine the incidence of OFC in Ontario, Canada, and to compare risk factors and mortality associated with children with OFC vs children without OFC. Design, Setting, and Participants: This population-based retrospective cohort study used health administrative data from the province of Ontario, Canada. Children with OFC who were born from April 1, 1994, to March 31, 2017, in Ontario were each matched to 5 children without OFC based on sex, date of birth (±30 days), and mother's age (±5 years). Analyses were conducted from September 2018 to January 2019. Exposures: Children born with OFC. Main Outcomes and Measures: Incidence of OFC over time and regional variation. Risk factors for OFC were assessed using 1-way analysis of variance for means, Kruskal-Wallis for medians, and χ2 tests for categorical variables. Adjusted Cox regression models were used to assess mortality. Results: From 1994 to 2017, 3262 children were born with OFC in Ontario, Canada, and they were matched to 15â¯222 children born without OFC. Incidence of OFC in Ontario was 1.12 cases per 1000 live births, with wide geographic variation and a lower incidence from 2004 to 2017 compared with 1994 to 2003 (1.02 vs 1.13 cases per 1000 live births; P = .002), especially for the subgroup with cleft palate (0.52 vs 0.44 cases per 1000 live births; P = .006). Children with OFC, compared with children without OFC, were more likely to be born prematurely (406 children [13.3%] vs 1086 children [7.1%]; P < .001; standardized difference, 0.21) and had lower mean (SD) birth weight (3215.3 [687.6] g vs 3382.6 [580.0] g; P < .001; standardized difference, 0.26). The mortality rate among children with OFC was higher than among matched children without OFC (hazard ratio, 10.60; 95% CI, 7.79-14.44; P < .001). When mortality was adjusted for the presence of congenital or chromosomal anomalies, the risk of death was not significantly different between children with OFC and those without OFC (hazard ratio, 1.35; 95% CI, 0.73-2.72). Conclusions and Relevance: These findings suggest that incidence of OFC In Ontario, Canada, decreased from 1994 to 2017. Mortality in children with OFC was high, especially in the first 2 years of life, and was predominantly associated with the presence of other congenital or chromosomal anomalies. Further research is required to better understand the causes of wide geographical variations of OFC incidence and improve the survival of these patients.
Assuntos
Fenda Labial , Fissura Palatina , Adulto , Fenda Labial/epidemiologia , Fenda Labial/mortalidade , Fissura Palatina/epidemiologia , Fissura Palatina/mortalidade , Feminino , Humanos , Incidência , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Ontário/epidemiologia , Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To ascertain how many fetuses with prenatally diagnosed cleft lip with or without cleft palate have associated congenital structural and/or chromosomal abnormalities and whether there is an association with the anatomical type of cleft lip or palate. METHODS: This was a retrospective review of infants referred to the North-West England Regional Cleft Lip and Palate (CLAP) team between January 2000 and January 2006. Referrals made to the Regional Fetal Management Unit (FMU) in the same time period were investigated to identify the corresponding antenatal ultrasound findings and data on termination of pregnancy and intrauterine fetal death. RESULTS: Over the 6-year period investigated, 570 infants were referred to the FMU and/or CLAP team. Among these, there were 24 terminations of pregnancy, two intrauterine fetal deaths and one early neonatal death identified. Data on 69 of the 543 patients that survived were incomplete. Of 188 cases with unilateral and 34 cases with bilateral cleft lip +/- palate there were no karyotypical abnormalities without other structural abnormalities. The incidence of associated structural abnormalities varied with the anatomical type of cleft: that of unilateral cleft lip +/- palate was 9.8% (19/194), that of bilateral cleft lip and palate was 25% (11/44) and that of midline cleft lip and palate was 100% (11/11). None of 252 cases with isolated cleft palate was identified antenatally; of these, 5.6% (n = 14) had either karyotypical or associated structural abnormalities and 21.0% (n = 53) had a genetic syndrome as an underlying diagnosis. CONCLUSIONS: It is essential to tailor the antenatal counseling of patients to the specific scan diagnosis, considering both the anatomical type of cleft and the presence or absence of associated abnormalities. It is inappropriate to offer invasive testing to all patients. The use of three-dimensional ultrasound as an adjunct should be considered in these patients to improve the accuracy of prenatal diagnosis.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Aberrações Cromossômicas/embriologia , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Anormalidades Múltiplas/mortalidade , Aborto Induzido/estatística & dados numéricos , Fenda Labial/genética , Fenda Labial/mortalidade , Fissura Palatina/genética , Fissura Palatina/mortalidade , Feminino , Humanos , Incidência , Recém-Nascido , Cariotipagem , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To investigate the clinical implications of two categories of fetal bilateral cleft lip and palate (BCLP): with premaxillary protrusion and with a flattened profile. METHODS: This was a retrospective study of fetuses with a prenatal diagnosis of BCLP at the Department of Obstetrics and Gynecology of the University of Bologna in the period 1991-2005. RESULTS: BCLP was diagnosed prenatally in 14 cases (mean gestational age at diagnosis, 21 (range, 12-36) weeks). In nine of these, there was a premaxillary pseudomass; in the remaining five, the profile was flat. Associated structural and/or chromosomal anomalies were found in two of the nine with a premaxillary pseudomass and in all five of those with a flat profile (P = 0.02). All fetuses with a flat profile had aneuploidies (three trisomy 18, one trisomy 13, one trisomy 8 mosaic), as did one of the nine with a premaxillary pseudomass. Eight of the pregnancies were terminated, including three of those with a premaxillary pseudomass and all five of those without. All continuing pregnancies resulted in live births, although one neonate affected by Krabbe's disease died shortly after birth. CONCLUSIONS: Our findings suggest that a third of cases of BCLP diagnosed in utero have a flat profile and these are at high risk of lethal aneuploidies.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Aneuploidia , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Maxila/diagnóstico por imagem , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/mortalidade , Fenda Labial/embriologia , Fenda Labial/mortalidade , Fissura Palatina/embriologia , Fissura Palatina/mortalidade , Feminino , Doenças Fetais/mortalidade , Idade Gestacional , Humanos , Recém-Nascido , Maxila/anormalidades , Maxila/embriologia , Gravidez , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
Mammals with excess insulin-like growth factor 2 (IGFII) during embryogenesis have developmental defects that can lead to perinatal lethality. In adults, higher levels of IGFII increase the risk of cancer and may accelerate the development of atherosclerosis. IGFII can be increased as a consequence of genetic abnormalities and polymorphisms, and through epigenetic mechanisms. Decreasing IGFII levels thus can benefit human health. Degradation of IGFII is mediated by the insulin-like growth factor type 2 receptor (IGF2R). The growth-stimulatory effects of IGFII, and their attenuation by the IGF2R, are considered important for the evolution of IGFII/IGF2R interaction and imprinting. The IGFII/IGF2R interactions during development have been previously examined in mice carrying knock-out alleles of these genes or their regulators. Here we tested the ability of the IGF2R to ameliorate the negative effects of IGFII on development and survival in crosses between Igf2 and Igf2r transgenic mice, which may be a better model for natural variations in the levels of these genes' products. A fraction of hemizygous Igf2 transgenic mice die in the perinatal period, some with cleft palates, with an ensuing reduction in the frequency of transgenic mice among the surviving offspring. The Igf2r transgene lowers the frequency of cleft palate and increases the percentage of Igf2 transgenic mice among the live offspring. These findings draw attention to the fact that Igf2-associated lethality selects for the retention of IGFII/IGF2R binding in present day mammals; it may have played a similar role in the acquisition of IGFII/IGF2R binding in ancient mammals.
Assuntos
Genes Letais , Fator de Crescimento Insulin-Like II/genética , Receptor IGF Tipo 2/fisiologia , Sobrevida/fisiologia , Animais , Fissura Palatina/genética , Fissura Palatina/mortalidade , Feminino , Impressão Genômica/genética , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismoRESUMO
BACKGROUND: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. DISCUSSION: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight.
Assuntos
Fenda Labial/terapia , Fissura Palatina/terapia , Avaliação de Resultados em Cuidados de Saúde , Fenda Labial/mortalidade , Fissura Palatina/mortalidade , Efeitos Psicossociais da Doença , Países em Desenvolvimento , Humanos , Lactente , Recém-Nascido , Consentimento Livre e Esclarecido , Capacitação em Serviço , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , América do SulRESUMO
Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form.
Assuntos
Anormalidades Múltiplas/genética , Amelogênese Imperfeita/genética , Caseína Quinase I/genética , Fissura Palatina/genética , Demência/genética , Diagnóstico Diferencial , Epilepsia/genética , Exoftalmia/genética , Proteínas da Matriz Extracelular/genética , Microcefalia/genética , Osteosclerose/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/fisiopatologia , Adolescente , Amelogênese Imperfeita/diagnóstico , Amelogênese Imperfeita/mortalidade , Amelogênese Imperfeita/fisiopatologia , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/mortalidade , Doenças do Desenvolvimento Ósseo/fisiopatologia , Fissura Palatina/diagnóstico , Fissura Palatina/mortalidade , Fissura Palatina/fisiopatologia , Demência/diagnóstico , Demência/mortalidade , Demência/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/mortalidade , Epilepsia/fisiopatologia , Exoftalmia/diagnóstico , Exoftalmia/mortalidade , Exoftalmia/fisiopatologia , Feminino , Humanos , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/fisiopatologia , Masculino , Microcefalia/diagnóstico , Microcefalia/mortalidade , Microcefalia/fisiopatologia , Osteosclerose/diagnóstico , Osteosclerose/mortalidade , Osteosclerose/fisiopatologia , Fenótipo , Convulsões/genética , Convulsões/fisiopatologiaRESUMO
OBJECTIVE: To quantify the burden of selected congenital anomalies in low and middle-income countries (LMICs) that could be reduced should surgical programmes cover the entire population with access to quality care. DESIGN: Burden of disease and epidemiological modelling. SETTING: LMICs from all global regions. POPULATION: All prevalent cases of selected congenital anomalies at birth in 2010. MAIN OUTCOME MEASURES: Disability-adjusted life years (DALYs). INTERVENTIONS AND METHODS: Surgical programmes for three congenital conditions were analysed: clefts (lip and palate); congenital heart anomalies; and neural tube defects. Data from the Global Burden of Disease 2010 Study were used to estimate the combination of fatal burden that could be addressed by surgical care and the additional long-term non-fatal burden associated with increased survival. RESULTS: Of the estimated 21.6 million DALYs caused by these three conditions in LMICs, 12.4 million DALYs (57%) are potentially addressable by surgical care among the population born with such conditions. Neural tube defects have the largest potential with 76% of burden amenable by surgery, followed by clefts (59%) and congenital heart anomalies (49%). Sub-Saharan Africa and South Asia have the greatest proportion of surgically addressable burden for clefts (68%), North Africa and Middle East for congenital heart anomalies (73%), and South Asia for neural tube defects (81%). CONCLUSIONS: There is an important and neglected role surgical programmes can play in reducing the burden of congenital anomalies in LMICs.