Microcefalia, defecto de crecimiento y retraso mental. Dificultades diagnósticas para el síndrome alcohólico fetal / Microcephaly, growth deficiency and mental retardation: diagnostic problems in fetal alcohol syndrome

El síndrome alcohólico fetal (SAF) se define como un defecto congénito permanente causado por el consumo excesivo de alcohol materno durante el embarazo. Se caracteriza por un crecimiento disminuido, una alteración del sistema nervioso central y un conjunto de alteraciones faciales menores. La incidencia estimada es de 0,33-2,2/1.000 recién nacidos vivos en Estados Unidos. Hasta los años noventa no hubo una serie de criterios unificados y objetivos para llegar al diagnóstico de SAF. Se presenta el caso clínico de un niño de 5 años y 10 meses con este síndrome. El objetivo de este artículo es revisar los criterios diagnósticos del SAF y su actualización

Fetal alcohol syndrome (FAS) is defined as a permanent birth defect syndrome caused by maternal alcohol abuse during pregnancy. It is characterized by growth deficiency, central nervous system (CNS) dysfunction and minor facial anomalies. The incidence in the USA has been estimated to be between 0.33 and 2.2 per 1000 live births. Until the 90’s, there were no objective, standardized criteria for the diagnosis of FAS. We report the case of a boy aged 5 years and 10 months who has been diagnosed as having this syndrome. The aim of this article is to review and update the criteria for the diagnosis of FAS

Neuropatía óptica inducida por exposición prenatal a drogas o alcohol / Optic neuropathy induced by prenatal drug or alcohol exposure

Objetivo: Nos proponemos analizar los mecanismos celulares y moleculares implicados en el desarrollo de la retina y el nervio óptico, y las consecuencias de un consumo abusivo de metanfetamina (MA) o alcohol (EtOH) durante la gestación sobre el sistema visual en desarrollo. Material y métodos: Ratas Wistar fueron expuestas a MA o EtOH durante la gestación y lactancia para obtener su descendencia. Los globos oculares y nervios ópticos de neonatos (días 7, 14, 21 postnatales) fueron procesados para técnicas morfológicas, morfométricas y Western Blot, utilizando anticuerpos frente a la proteína fibrilar ácida de la glía (GFAP) y proteína básica de la mielina (MBP) y proteína de los neurofilamentos (NFP). Resultados: Observamos diferencias estadísticamente significativas entre el grupo expuesto a MA y expuesto a EtOH frente a los controles. El tamaño de la sección transversal del nervio óptico fue inferior en relación a la exposición a drogas o alcohol. La expresión de GFAP y MBP está alterada en los animales expuestos a drogas o alcohol, respecto a los controles. Conclusiones: La exposición prenatal a psicoestimulantes o alcohol altera el desarrollo de la retina y nervio óptico

Purpose: The main aim of this work was to analyse the cellular and molecular mechanisms involved in retinal and optic nerve development, and the consequences of methamphetamine "ice" (MA) or alcohol (EtOH) abuse during pregnancy on the developing visual system. Material and methods: Wistar rats were exposed to MA or EtOH during gestation and lactation and their offspring studied. Control isocaloric rats were maintained in parallel. The eyes and optic nerves from pups (at 7, 14 and 21 postnatal days) were processed using morphologic, morphometric and western blot approaches using antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and neurofilament protein (NFP). Results: Statistically significant differences were observed between the methamphetamine-exposed and the alcohol-exposed rats, as compared to the controls. The optic nerve cross-sectional area was smaller in the drug or alcohol-exposed animals. The expression of developmental protein markers (GFAP and MBP) in the retina and optic nerve displayed striking alterations related to drug or alcohol abuse during gestation and lactation. Conclusions: Psychostimulant and alcohol exposure alters the development of the retina and optic nerve

The neurodevelopmental consequences of prenatal alcohol exposure.

During pregnancy, ingestion of alcohol, a known teratogen, can cause harm to the fetus. Prenatal alcohol exposure is one of the leading causes of birth defects, developmental disorders, and mental retardation in children. The fetal central nervous system is particularly vulnerable to alcohol; this vulnerability contributes to many of the long-term disabilities and disorders seen in individuals with prenatal alcohol exposure. Diagnoses associated with prenatal alcohol exposure include fetal alcohol syndrome (FAS), partial fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects. Once diagnosed, early intervention improves the long-term outcome of affected children. Without documentation of maternal alcohol use, a diagnosis, and consequently treatment, is often difficult to attain. It is imperative that nurses, physicians, and other healthcare providers become comfortable with obtaining a history of, and providing anticipatory guidance and counseling about, alcohol use.

Fetal alcohol spectrum disorders.

To complement the 2005 Annual Clinical Focus on medical genomics, AFP will be publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the kind of care they might require in the future. The second review in this series discusses fetal alcohol syndrome and fetal alcohol spectrum disorders.

Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia.

Neuroanatomical and behavioral evidence indicate that the cerebellum is particularly vulnerable to the toxic effects of prenatal alcohol exposure. Recent research has shown impairments in eyeblink conditioning in rats following binge-like neonatal ethanol exposure. The neural substrates of eyeblink conditioning have been localized to the cerebellum and related brainstem mechanisms. The present study considered whether heavy prenatal alcohol exposure would result in similar impairments in eyeblink conditioning in children. A related purpose was to determine if eyeblink conditioning could discriminate between children with prenatal alcohol exposure and children diagnosed with attention deficit hyperactive disorder or developmental dyslexia. Fifty-three age-matched children [10 prenatal alcohol exposure (FAE), 16 attention deficit hyperactive disordered (ADHD), 14 children with dyslexia (DYS), 13 normal controls] were assessed on eyeblink conditioning in the delay paradigm. Children in the FAE and DYS groups failed to learn the conditioned response, producing longer latencies and poorly timed responses to the conditioning stimulus. Children with ADHD were impaired on measures of adaptively timed responses, although conditioned responses matched normal controls. The results suggest that children prenatally exposed to alcohol have deficits in cerebellar processing similar to those with dyslexia, and that these functional deficits are related to disabilities in learning.

Fetal alcohol syndrome and pyloric stenosis: alcohol induced or an association?

We report a newborn with fetal alcohol syndrome with severe feeding intolerance and failure to thrive due to pyloric stenosis. This illustrates the importance of early recognition of pyloric stenosis in fetal alcohol syndrome to improve nutrition and growth. We speculate that pyloric stenosis in neonates results from the absence or immaturity of intrinsic nitric oxide synthase-containing neurons in the pyloric muscle in children of alcohol-addicted mothers.

"Do I know what I need to do?" A social communication intervention for children with complex clinical profiles.

PURPOSE: Speech-language pathologists frequently address social communication difficulties in children with diverse clinical profiles. The purpose of this study was to investigate the feasibility of a social communication intervention for a school-age child with a complex cognitive and behavioral profile secondary to diagnosis of a fetal alcohol spectrum disorder. METHOD: A case study is presented to describe the implementation of the intervention targeting mental state verb production and social cognitive skills. The intervention included group role play of social scripts and a checklist to elicit the participant's statements about others' perspectives and strategies for completing the social script. Treatment data monitored the participant's responses to the checklist questions. Probe sessions, consisting of theory of mind false belief tasks, were used to examine mental state verb use. RESULTS: Treatment data demonstrated that the participant stated more strategies in response to checklist questions. The participant did not produce any mental state verbs during baseline probes, but did produce mental state verbs during the treatment phase. CLINICAL IMPLICATIONS: The results support use of this intervention to change children's linguistic and social cognitive skills. Suggestions for extending this intervention to include a generalization plan targeting classroom social communication interactions are provided.

Fetal alcohol syndrome in association with Rett syndrome.

Fetal alcohol syndrome in association with RETT syndrome: We report on a girl with neonatal dystrophy, microcephaly, heart defect, and the characteristic features of alcohol embryopathy. Later, she developed distinctive features of RETT syndrome including loss of early acquired developmental skills and presented typical symptoms of RETT syndrome as reduction of communication skills, reduction of hand function, hyperventilation, and grinding of teeth. Molecular analysis of the MECP2 gene revealed the c.808T>C (R270X) mutation located in the nuclear localisation signal sequence of the gene. Our report highlights the importance of considering the diagnosis of RETT syndrome even in patients who are already suffering from a defined disease.

Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

The challenge of fetal alcohol syndrome in the criminal legal system.

People with fetal alcohol spectrum disorder (FASD) present challenges to those who work in the criminal legal system. Prenatal exposure to alcohol can cause physical, neurological, and psychological impairments. It is vital to understand the individual offender in order to address the underlying reasons for criminal behavior. Individuals with FASD often come from dysfunctional backgrounds, and may have mental illnesses and substance use disorders. A comprehensive medical-legal report, prepared by a professional experienced with FASD, can help judges and lawyers understand how complex the interactions are among brain damage, genetics, and the environment. The person with FASD can be misunderstood in court, victimized in jails, and mismanaged in the transition back to the community, unless those working with the individual are aware of FASD and its implications.

Síndrome alcohólico fetal. Criterios diagnósticos. Hallazgos en 13 casos estudiados / Fetal alcohol syndrome: diagnostic criteria and findings in 13 cases

El síndrome alcohólico fetal (SAF) es un conjunto de signos clínicos que se presentan en el feto tras la exposición intrauterina al alcohol. Es conocido que el alcohol es el agente teratógeno más frecuente en el ser humano, así como que sus efectos pueden ser evitados, si se elimina la ingestión de alcohol durante el embarazo. Tras el consumo, incluso de pequeñas cantidades, pueden aparecer una serie de signos físicos, neurológicos y conductuales que constituyen el síndrome. En este artículo se hace una actualización simplificada de los criterios diagnósticos del síndrome alcohólico fetal. Se señalan los aspectos principales del metabolismo del alcohol, sus relaciones con la placenta y los posibles mecanismos mediante los que ejerce su acción teratógena. Igualmente, se exponen las características clínicas de 13 casos diagnosticados en nuestro centro en los últimos 5 años (AU)

QT prolongation in the newborn and maternal alcoholism.

I discuss a newborn whose mother is addicted to alcohol. On the third day of life, the newborn was found to have ventricular tachycardia. After spontaneous termination of the abnormal rhythm, the duration of the corrected QT interval was 0.48 s. During the next days, the duration of the interval normalized, and has now remained stable for 5 years. I conclude that the so-called "alcohol withdrawal syndrome of the newborn" might cause postnatal prolongation of the QT interval.

A comparison of the effects of parental risk markers on pre- and perinatal variables in multiple patient cohorts with fetal alcohol syndrome, autism, Tourette syndrome, and sudden infant death syndrome: an enviromic analysis.

The prevalence and magnitude of effect of individual risk markers for specific developmental disorders vary widely across diagnostic category. The four study cohorts for this project were patients from four diagnostic registries in North Dakota for fetal alcohol syndrome (FAS), autism, sudden infant death syndrome (SIDS), and Tourette syndrome. These four cohorts were used to estimate prevalence and magnitude of effect of parental risk markers in patients with developmental disabilities. Cases with North Dakota birth certificates were matched with controls. Using birth certificate data, we then examined five parental risk markers for each cohort and estimated direct and indirect effects for each risk marker by cohort. The authors found two significant paternal risk markers (age in SIDS and education in FAS). Significant maternal markers were age in SIDS, education in FAS, autism, and SIDS. Marital status was a significant risk marker in FAS. Effect sizes were estimated using paired t tests, odds ratios, and population attributable risk (PAR) for both direct and indirect effects for each marker. We estimated both direct and indirect effects to allow for direct comparisons of the differential effect estimates of each of these markers. The direct effect of parental markers differs across diagnostic cohorts of patients. Use of cohorts from similar denominator populations obtained from prevalence studies is a useful methodological tool for estimating the prevalence and magnitude of effect of risk markers.

Fetal alcohol syndrome: neuropsychiatric phenomics.

Fetal alcohol syndrome (FAS) is a common developmental disorder with impairments in multiple neuropsychiatric spheres of varying severity. Few population-derived studies of the behavioral phenotype are available. The purpose of this study was to estimate the prevalence of neuropsychiatric disorders in three groups: subjects who met criteria for FAS (n=152); subjects who met criteria for partial FAS/ARND (n=150); and referred subjects who did not meet criteria for either FAS or partial FAS/ARND (n=86). Each subject had a standardized evaluation by a medical geneticist. All subjects were from North Dakota. We found increases in the prevalence rates of neuropsychiatric disorders in subjects with FAS compared to subjects with partial FAS/ARND and the lowest rates in the group that did not meet criteria for either FAS or partial FAS/ARND. Comorbid attention deficit hyperactivity disorder occurred in 73% of cases with FAS, in 72% cases with partial FAS/ARND, and in 36% subjects who did not meet criteria for either. For other neuropsychiatric disorders, a similar distribution of comorbidity was found. This study supports the concept of a continuum of impairment resulting from prenatal alcohol exposure. The presence of complex cognitive, behavioral, and physical symptomatology in the affected subjects with prenatal alcohol exposure would seem to fit well under the diagnostic rubric of fetal alcohol spectrum disorder (FASD). Diagnosis and long-term management will require increasing access to multidisciplinary child development teams including mental health professionals who treat children and adolescents. Adults will require care primarily from teams with expertise in mental health and developmental disabilities.

Children with Fetal Alcohol Syndrome are impaired at place learning but not cued-navigation in a virtual Morris water task.

We employed a computerized (virtual) Morris water task (VMWT) to measure place learning and cued-navigation in eight adolescent males (9.5-16.5 years old) diagnosed with Fetal Alcohol Syndrome (FAS). Eight adolescent males matched for age and ethnicity with no history of prenatal alcohol exposure served as controls. Participants were trained to navigate to a hidden platform in a fixed location relative to a set of four conspicuous extramaze cues. After 20 hidden platform trials, a single no-platform probe trial was conducted, followed by 8 trials during which the platform was visible (cued-navigation). The FAS group traveled further than controls to navigate to the hidden platform during training. During the probe trial, controls navigated more directly to the platform region and persisted in searching where the platform had been more than the FAS group. Cued-navigation was comparable in both groups, suggesting that group differences in place learning were not attributable to visual-motor or motivational deficits in the FAS subjects. This pattern of impaired place learning and spared cued-navigation is similar to that reported in rats exposed to ethanol during periods of prenatal or early postnatal brain growth, as well as in animals with hippocampal damage.

Fetal alcohol syndrome in developmental age. Neuropsychiatric aspects.

Alcohol constitutes one of the main risk factors for the health of the newborn infant and is also one of the leading causes of cognitive deficit. The distinctive pattern of abnormalities that characterizes fetal alcohol syndrome (FAS) includes: pre- and postnatal growth retardation, cognitive deficit, behavior and language disorders, cerebral malformations (schizencephaly, polymicrogyria, agenesis of the corpus callosum), facial changes (short palpebral fissures, low nasal bridge, anomalies of the auricle, maxillary hypoplasia, cleft lip and palate) and organ anomalies (heart defects, renal and skeletal malformations). As occurs with any teratogenic agent, the variability of phenotypic expression is wide and depends on dose, gestational stage, duration of exposure, maternal and fetal metabolism and other environmental and genetic factors. This study describes 6 subjects with FAS who express various characteristics of the clinical spectrum of the syndrome.

Behavioural phenotype in foetal alcohol syndrome and foetal alcohol effects.

A sample of 12 children (seven males, five females; mean age 6 years 7 months, SD 2 years 6 months, range 2 years 4 months to 12 years 1 month) with moderate-to-severe foetal alcohol syndrome (FAS) and another sample of 26 children (12 males, 14 females; mean age of 6 years 2 months SD 2 years 10 months, range 2 years 6 months to 12 years 8 months) with mild FAS or foetal alcohol effects (FAE) as well as a sample of 15 age- and sex-matched control children with unspecific intellectual disability were compared using the Developmental Behaviour Checklist (DBC). There were significant differences (p=0.01) between the groups on five of six subscales of the DBC with controls scoring lower on the disruptive, self-absorbed, anxiety, antisocial behaviour, and communication disturbance scales. The DBC profiles of the two foetal alcohol exposed groups did not differ from each other. It is concluded that quantitative behaviour measurement provides insights into specific behavioural phenotypes of FAS/FAE.