RESUMO
Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.
RESUMO
Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = -0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.
Assuntos
Anormalidades Congênitas/epidemiologia , Anormalidades do Olho/epidemiologia , Cooperação Internacional , Vigilância da População/métodos , Adulto , América/epidemiologia , Austrália/epidemiologia , Pesquisa Biomédica/tendências , China/epidemiologia , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Anormalidades Congênitas/genética , Anormalidades Congênitas/patologia , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Feminino , Holoprosencefalia/epidemiologia , Holoprosencefalia/genética , Holoprosencefalia/patologia , Humanos , Recém-Nascido , Masculino , Gravidez , Prevalência , Sistema de Registros , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13RESUMO
Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32-1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature.
Assuntos
Anormalidades Congênitas/epidemiologia , Doenças em Gêmeos/epidemiologia , Cooperação Internacional , Vigilância da População/métodos , Gêmeos Unidos , Gêmeos Monozigóticos , América/epidemiologia , Austrália/epidemiologia , Pesquisa Biomédica/tendências , China/epidemiologia , Anormalidades Congênitas/patologia , Doenças em Gêmeos/patologia , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Prevalência , Sistema de Registros , Razão de Masculinidade , Gêmeos Unidos/patologiaRESUMO
Sirenomelia is a very rare limb anomaly in which the normally paired lower limbs are replaced by a single midline limb. This study describes the prevalence, associated malformations, and maternal characteristics among cases with sirenomelia. Data originated from 19 birth defect surveillance system members of the International Clearinghouse for Birth Defects Surveillance and Research, and were reported according to a single pre-established protocol. Cases were clinically evaluated locally and reviewed centrally. A total of 249 cases with sirenomelia were identified among 25,290,172 births, for a prevalence of 0.98 per 100,000, with higher prevalence in the Mexican registry. An increase of sirenomelia prevalence with maternal age less than 20 years was statistically significant. The proportion of twinning was 9%, higher than the 1% expected. Sex was ambiguous in 47% of cases, and no different from expectation in the rest. The proportion of cases born alive, premature, and weighting less than 2,500 g were 47%, 71.2%, and 88.2%, respectively. Half of the cases with sirenomelia also presented with genital, large bowel, and urinary defects. About 10-15% of the cases had lower spinal column defects, single or anomalous umbilical artery, upper limb, cardiac, and central nervous system defects. There was a greater than expected association of sirenomelia with other very rare defects such as bladder exstrophy, cyclopia/holoprosencephaly, and acardia-acephalus. The application of the new biological network analysis approach, including molecular results, to these associated very rare diseases is suggested for future studies.
Assuntos
Anormalidades Congênitas/epidemiologia , Ectromelia/epidemiologia , Cooperação Internacional , Vigilância da População/métodos , Adulto , América/epidemiologia , Austrália/epidemiologia , Pesquisa Biomédica/tendências , China/epidemiologia , Anormalidades Congênitas/patologia , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/patologia , Ectromelia/patologia , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Idade Materna , Gravidez , Prevalência , Sistema de Registros , Adulto JovemRESUMO
OBJECTIVES: To identify preferential associations between oral clefts (CL = cleft lip only, CLP = cleft lip with cleft palate, CP = cleft palate) and nonoral cleft anomalies, to interpret them on clinical grounds, and, based on the patterns of associated defects, to establish whether CL and CLP are different conditions. DESIGN AND SETTINGS: Included were 1416 cleft cases (CL = 131, CLP = 565, CP = 720), among 8304 live- and stillborn infants with multiple congenital anomalies, from 6,559,028 births reported to the International Clearinghouse for Birth Defects Surveillance and Research by 15 registries between 1994 and 2004. Rates of associated anomalies were established, and multinomial logistic regressions applied to identify significant associations. RESULTS: Positive associations with clefts were observed for only a few defects, among which anencephaly, encephaloceles, club feet, and ear anomalies were the most outstanding. Anomalies negatively associated with clefts included congenital heart defects, VATER complex (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia), and spina bifida. CONCLUSION: The strong association between all types of clefts and anencephaly seems to be attributable to cases with disruptions; the association between CP and club feet seems to be attributable to conditions with fetal akinesia. Some negative associations may depend on methodologic factors, while others, such as clefts with VATER components or clefts with spina bifida, may depend on biological factors. The different patterns of defects associated with CL and CLP, indicating different underlying mechanisms, suggest that CL and CLP reflect more than just variable degrees of severity, and that distinct pathways might be involved.