RESUMO
OBJECTIVES: The purpose of this study was to demonstrate that a quantitative, multivariate case definition of the fetal alcohol syndrome (FAS) facial phenotype could be derived from photographs of individuals with FAS and to demonstrate how this case definition and photographic approach could be used to develop efficient, accurate, and precise screening tools, diagnostic aids, and possibly surveillance tools. STUDY DESIGN: Frontal facial photographs of 42 subjects (from birth to 27 years of age) with FAS were matched to 84 subjects without FAS. The study population was randomly divided in half. Group 1 was used to identify the facial features that best differentiated individuals with and without FAS. Group 2 was used for cross validation. RESULTS: In group 1, stepwise discriminant analysis identified three facial features (reduced palpebral fissure length/inner canthal distance ratio, smooth philtrum, and thin upper lip) as the cluster of features that differentiated individuals with and without FAS in groups 1 and 2 with 100% accuracy. Sensitivity and specificity were unaffected by race, gender, and age. CONCLUSIONS: The phenotypic case definition derived from photographs accurately distinguished between individuals with and without FAS, demonstrating the potential of this approach for developing screening, diagnostic, and surveillance tools. Further evaluation of the validity and generalizability of this method will be needed.
Assuntos
Fácies , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Fenótipo , Fotografação , Adolescente , Adulto , Criança , Pré-Escolar , Análise Discriminante , Feminino , Humanos , Lactente , Recém-Nascido , Lábio/patologia , Masculino , Sensibilidade e EspecificidadeRESUMO
This study was undertaken to evaluate teratogenesis associated with early weekly ethanol exposure followed by later gestational abstinence. Ethanol, 1.8 gm/kg, was orally administered weekly to gravid nonhuman primates (Macaca nemestrina) for the first 3, 6, or the entire 24 weeks of pregnancy. Control animals received weekly sucrose solution as did the 3- and 6-week cohort animals in subsequent weeks. Thirty-five viable infants were assessed for growth, malformations, and behavioral and cognitive dysfunction. Animals in the 6-week and 24-week cohorts were uniformly abnormal in behavior and inconsistently abnormal in physical development relative to the control animals. Animals in the 3-week cohort were equivocally normal. These results demonstrate ethanol's capacity to produce behavioral teratogenesis (brain dysfunction) in isolation from physical anomalies in the rest of the body. The results strongly suggest that binge drinking in the first 6 to 8 weeks of pregnancy (a period when women may not know that they are pregnant), followed by later gestational abstinence, is as dangerous to the fetus as exposure throughout gestation.
Assuntos
Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Etanol/toxicidade , Feto/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Feminino , Crescimento/efeitos dos fármacos , Macaca nemestrina , Masculino , Memória/efeitos dos fármacos , Destreza Motora/efeitos dos fármacosRESUMO
Four unrelated patients who had the clinical appearance of Miller-Dieker syndrome, also called lissencephaly syndrome, were studied. All four had a typical clinical course with failure to thrive, severe psychomotor retardation, opisthotonos, seizures, and death early in life. None of these children had lissencephaly, the anticipated central feature of this disorder. One of the four had pachygyria, one had polymicrogyria, and two had both pachygyria and polymicrogyria. The brain weights were normal to decreased. The ventricles were dilated in all cases. The cerebral cortex was thickened in each, with decreased white matter and diminution or distortion of the cellular layers, and there were neuroglial heterotopias. The corpus callosum was partially absent in one and thinned in three. The neuropathy found in these children with Miller-Dieker syndrome suggests a spectrum of gyral anomalies resulting from a single type of embryonic error.
Assuntos
Encéfalo/anormalidades , Agenesia do Corpo Caloso , Encéfalo/patologia , Córtex Cerebral/anormalidades , Ventrículos Cerebrais/anormalidades , Doenças em Gêmeos , Feminino , Humanos , Recém-Nascido , Masculino , Espasticidade Muscular/etiologia , Neuroglia/patologia , Tamanho do Órgão , Transtornos Psicomotores/etiologia , Convulsões/etiologia , SíndromeRESUMO
Two siblings are reported who appear to have an autosomal recessive disorder of eye and central nervous system anomalies. The findings in fourteen previously described and similarly affected patients are summarized. Ocular anomalies include microphthalmos, megalocornea, the Peter anomaly, cataract, coloboma, persistent hyperplastic primary vitreous, and retinal detachment with retinal dysplasia. Central nervous system malformations include agyria-pachygyria, cerebellar dysplasia, encephalocele, Dandy-Walker cyst, and hydrocephalus. We suggest that this disorder be known as Warburg syndrome.
Assuntos
Encéfalo/anormalidades , Aberrações Cromossômicas/genética , Anormalidades do Olho , Encefalopatias/etiologia , Encefalopatias/genética , Transtornos Cromossômicos , Oftalmopatias/etiologia , Oftalmopatias/genética , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome , Terminologia como AssuntoRESUMO
Ethanol was administered nasogastrically to four gravid pigtailed macaques (Macaca nemestrina) weekly from 40 days after conception to term. Three animals received 2.5 gm/kg and one received 4.1 gm/kg per dose. One animal aborted after the first dose of 2.5 gm/kg ethanol. Serum ethanol and acetaldehyde were measured after each dose in the other three animals, who carried to term. After delivery the infants were assessed for growth, dysmorphic features, and neurologic and psychological development over six months and were compared with 10 age- and sex-matched controls. Complete autopsies with neuropathologic examinations were performed. The animal exposed to the high dose had neurologic, developmental, and facial anomalies similar to those seen in human fetal alcohol syndrome. One of the animals exposed to the more moderate dosage was similarly but less severely affected. The study demonstrates that a model for binge drinking and fetal alcohol syndrome can be developed in a primate. The model should be useful in exploring the mechanisms of teratogenesis and in determining the median effective dose for the production of the various anomalies seen in fetal alcohol syndrome.
Assuntos
Consumo de Bebidas Alcoólicas , Transtornos do Espectro Alcoólico Fetal/patologia , Modelos Biológicos , Animais , Encéfalo/patologia , Etanol/sangue , Expressão Facial , Feminino , Transtornos do Espectro Alcoólico Fetal/sangue , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Humanos , Recém-Nascido , Macaca nemestrina , Masculino , Exame Neurológico , Gravidez , Crânio/patologiaRESUMO
Plagiocephaly usually originates in late fetal life through aberrant constraint of the fetal head and is often associated with sternocleidomastoid torticollis. In some patients the obligue head shape may become a permanent, cosmetic disability. Individually fitted plastic helmets, similar in style to football helmets, have been successfully used to remold the deformed heads of four infants. Each helmet is designed to fit snugly against the prominent aspects of the infants' cranium and to be loose fitting where the head is shallow. As the brain grows, the head is molded to fit the helmet and thus acquires a more usual shape. The treatment has been safe and effective. When torticollis is persistent after the initiation of treatment, rubber straps can be fixed to the outside of the helmet and attached to the side rails of the crib. While the infant sleeps, the straps can be tightened to stretch the shortened sternocleidomastoid muscle.
Assuntos
Crânio/anormalidades , Torcicolo/congênito , Moldes Cirúrgicos , Cabeça , Humanos , Lactente , Métodos , Restrição Física , Torcicolo/terapiaRESUMO
Hyperthermia has been shown to be a teratogenic agent in a number of animal species. We have attempted to determine if maternal hyperthermia during early gestation might also be responsible for problems in human development. Eight retrospectively ascertained cases, in which high fever had occurred at four to six weeks' gestation, revealed a similar clinical phenotype in the infants despite the fact that the maternal fever was caused by different infections. The most consistent manifestations were severe mental deficiency, seizures, hypotonia, microphthalmia, midface hypoplasia, and mild impairment of distal limb development. In five patients exposed to hyperthermia at seven to 16 weeks' gestation, predominant features were hypotonia, neurogenic arthrogryposis, and central nervous system dysgenesis. The cause of fever differed in each of these cases; in one, a patient with neurogenic arthrogryposis, the hyperthermia had been induced in a sauna bath. No apparent serious problem in morphogenesis was found following hyperthermia during the latter half of gestation. These findings are similar to those resulting from induced hyperthermia in animals. Further research on the effects of hyperthermia in the developing human being seems warranted.
Assuntos
Anormalidades Congênitas/etiologia , Febre/complicações , Complicações na Gravidez , Aborto Espontâneo/etiologia , Artrogripose/etiologia , Sistema Nervoso Central/embriologia , Eletroencefalografia , Feminino , Febre/etiologia , Idade Gestacional , Humanos , Recém-Nascido , Deficiência Intelectual/etiologia , Microftalmia/etiologia , Morfogênese , Tono Muscular , Gravidez , Convulsões/etiologiaRESUMO
Microcephaly and mental retardation have been principal features of the fetal alcohol syndrome. This article describes the neuropathologic findings in four human neonates who were exposed to large quantities of ethanol at frequent intervals during gestation. The findings suggest that intrauterine exposure to ethanol can result in structural abnormalities of the brain. All four brains displayed similar malformations stemming from errors in migration of neuronal and glial elements. Hydrocephalus was one consequence of the malformations in two of the infants. Futhermore, the brain alterations may be the only distinct abnormality produced by in utero ethanol exposure. Only two of the four subjects were diagnosed as having the fetal alcohol syndrome from external criteria.