Universal screening for autism spectrum disorder (ASD) is recommended during pediatric primary care visits in the first 2 years of life. However, many children are missed by initial screening and not diagnosed with ASD until years later. Research efforts are underway to develop and evaluate new objective measures of risk for ASD that can be used in infancy, before symptoms emerge. Initial studies with these tests, particularly MRI-based screening for infants at high familial risk, have shown promise but have not yet been evaluated in clinical trials. We present the study design for a hypothetical clinical trial that would combine presymptomatic detection and intervention for ASD and consider, through commentaries from diverse perspectives, the ethical issues that should be anticipated in advance of beginning such trials. Commentators Drs Pruett and Piven address the social value of the proposed research and importance of researcher-bioethicist collaborations. Drs Estes and Wolff discuss the clinical potential and challenges of developing presymptomatic interventions for infants at risk for ASD. Dr Harrington takes a neurodiversity view of presymptomatic prediction and intervention and their implications for autistic identity and quality of life. Finally, Drs MacDuffie, Peay and Wilfond consider the potential risks and benefits that must be evaluated and weighed in the next phases of research on presymptomatic detection and intervention for ASD.
OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X syndrome. METHOD: Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2–18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study. RESULTS: Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses. CONCLUSIONS: This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition.
Objective. Postmortem studies of fetuses, infants, and young children with fetal alcohol syndrome (FAS) have demonstrated a variety of severe central nervous system (CNS) anomalies. We undertook this magnetic resonance study (1) to assess the spectrum of CNS anomalies that occur in a clinical sample of typical patients with FAS who are medically stable; and (2) to examine the relationship between CNS and facial anomalies. Methodology. Magnetic resonance imaging was performed on a series of 10 patients (4 children, 3 adolescents, and 3 adults) who met criteria for FAS. We systematically evaluated each scan for brain anomalies and compared total brain tissue volume with that of healthy child, adolescent, and adult control subjects. Results. Six patients had some type of midline anomaly, ranging from partial to complete callosal agenesis (three patients) to hypoplastic corpus callosum (one patient), cavum septi pellucidi (three patients), and cavum vergae (two patients). These midline anomalies were associated with a greater number of facial anomalies. Other brain anomalies identified included micrencephaly, ventriculomegaly, and hypoplasia of the inferior olivary eminences. Conclusion. Patients with classic FAS have a high incidence of midline brain anomalies. This finding is consistent with the concept that the midline CNS is a developmental field that is particularly susceptible to the teratogenic effects of alcohol. Furthermore, patients with more severe facial dysmorphologic characteristics are more likely to have midline brain anomalies. In addition, we observed a high incidence of micrencephaly with a wide range of severity.
During the last decade considerable advances have been made in clinical, epidemiologic, and biologic research of autism. Although there are still no definitive answers, and an effective treatment remains elusive, these advances have provided new and important clues about etiologies and mechanisms of this disorder. The etiologies of autism are all highly likely to be neurobiologic; prenatal and perinatal events provide neither a necessary nor sufficient explanation for autism. Autism is one of the developmental disorders of brain function, not a disease. It is a syndrome defined by a characteristic set of behaviors which include (1) qualitative impairment in reciprocal social interaction, (2) qualitative impairment of verbal and nonverbal communication and imaginative activity, and (3) a markedly restricted repertoire of activities and interests. These tend to cluster together and are associated with a more or less predictable course. As is the case with all clinically defined syndromes such as dyslexia, epilepsy, or congestive heart failure, autism does not have a single etiology. Several etiologies are already known or suspected, and it is unlikely that a single pathophysiologic mechanism will account for all the cases. It is possible, however, that these different pathologies may impinge on a particular brain system of connected regions whose dysfunction is responsible for the common behavioral syndrome that links mildly and severely affected children. Pediatricians are likely to be the first professionals consulted by parents concerned about their child's developmental achievement. Severely deficient or aberrant developmental lags are unlikely to be overooked, but the significance of more subtle abnormalities in toddlers and preschool children and of the differential diagnosis even in overt disorders of cerebral function is often less certain.
Infantile autism was first described by Kanner in 1943.1 Based on the observation that symptoms often began shortly after birth and always by two or three years of age, Kanner believed that autism was caused by an unknown, inborn defect. Because this syndrome was so severe and peculiar, it seemed unlikely to be an understandable outcome of a child's life experiences. In the years since Kanner first described this disorder, research findings have supported his initial interpretations. It is now generally accepted that autism has a biologic cause, and considerable research has been carried out with the aim of uncovering its nature. Both hereditary factors and the prenatal and perinatal environment have been considered. This paper will review the role of genetic factors in the cause of autism; the role of the prenatal and perinatal environment is considered in the paper by Nelson.51 Three types of genetic associations have been described: (1) the familial aggregation of autism, per se—autism is more common in the sibs of affected children; (2) the familial aggregation of other disorders in the family members of autistic children—a variety of disorders that are mild, but probably conceptually related, have recently been described in relatives; and (3) autism appears in association with a few particular disorders of known genetic etiology. FAMILIAL AGGREGATION OF AUTISM Population and Family Studies In most case series and a few population-based studies, the prevalence of autism in the siblings of autistic children has been estimated to be about 2% to 3%.2,3 While this number is small, it is 50 to 100 times greater than the expected rate of autism of 4 to 5 per 10 000 in the population.4,5