Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2+) currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca(2+) overload in multiple cell types. In the heart, prolonged Ca(2+) current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism.

The Kiddie Schedule for Affective Disorders and Schizophrenia was modified for use in children and adolescents with autism by developing additional screening questions and coding options that reflect the presentation of psychiatric disorders in autism spectrum disorders. The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL), was piloted and frequently diagnosed disorders, depression, ADHD, and OCD, were tested for reliability and validity. The ACI-PL provides reliable DSM diagnoses that are valid based on clinical psychiatric diagnosis and treatment history. The sample demonstrated a high prevalence of specific phobia, obsessive compulsive disorder, and ADHD. The rates of psychiatric disorder in autism are high and are associated with functional impairment.

Autism involves primary impairments in both language and communication, yet in recent years the main focus of research has been on the communicative deficits that define the population. The study reported in this paper investigated language functioning in a group of 89 children diagnosed with autism using the ADI-R, and meeting DSM-IV criteria. The children, who were between 4-and 14-years-old were administered a battery of standardized language tests tapping phonological, lexical, and higher-order language abilities. The main findings were that among the children with autism there was significant heterogeneity in their language skills, although across all the children, articulation skills were spared. Different subgroups of children with autism were identified on the basis on their performance on the language measures. Some children with autism have normal language skills; for other children, their language skills are significantly below age expectations. The profile of performance across the standardized measures for the language-impaired children with autism was similar to the profile that defines the disorder specific language impairment (or SLI). The implications of this language impaired subgroup in autism for understanding the genetics and definition of both autism and SLI are discussed.Autism is diagnosed on the basis of abnormalities or impaired development in three areas: social interaction, communication, and a severely restricted repertoire of activity and interests, present before the age of three (APA, 1994). In the domain of communication, one criterion that is used to document the presence of autistic disorder is the delay or absence of spoken language. Indeed, this feature is important in differentiating between autism and another related developmental disorder, Asperger's syndrome, which is only diagnosed when there is no clinical delay in language (APA, 1994;Szatmari, 1998;Volkmar & Klin, 1998). Problems in language are central to our understanding of autism: they are often the first presenting symptom (Kurita, 1985;Lord & Paul, 1997); they vary widely in the population; and are the most important feature for predicting the prognosis and developmental course of children with this disorder (Rutter, 1970;Ventner, Lord, & Schopler, 1992).Despite the significance of language impairment in the diagnosis of autism, in recent years few studies have addressed this area of functioning. Instead, research on the nature of the language and communication deficits in autism has focused almost exclusively on those aspects that are universal and specific to this disorder (Tager-Flusberg, 1996). Beginning with Baltaxe (1977), studies have explored the pragmatic deficits that are apparent in conversations and other discourse contexts, identifying those features that distinguish communication problems in autism from those found in other clinical groups. This body of research has led to the consensus that children with autism are seriously limited in their communicative abilities (see Address Lord & Pa...

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

The ability to attribute 2nd-order mental states was investigated in 87 children drawn from preschool, kindergarten, lst-grade, and 2nd-grade classes. Children received 4 stories, 2 standard and 2 new, designed to test their understanding of 2nd-order mental states. The standard stories were modified versions of J. Perner and H. Wimmer's (1985) 2nd-order task. The new stories were made significantly simpler by reducing the number of characters, episodes, and scenes and by including a deception context. The main findings were that performance on the new stories was significantly better than on the standard stories and that nearly half of the preschoolers and almost all of the kindergartners were able to attribute 2nd-order beliefs. These findings contrast with earlier research.A strong consensus has emerged among theory-of-mind researchers that children first become capable of attributing mental states like belief at about the age of 4. Many researchers (e.g., Perner, 1991;Wellman, 1990) have noted, however, that the capacity to attribute second-order, or embedded, mental states (e.g., "She thinks that he thinks . . .") confers on children the capacity to understand not only a person's perception of a social situation (first-order reasoning) but also different individuals' concern about the other's mental states (second-order reasoning). It is these sorts of attributions that underlie much of our social reasoning and that are necessary for any sophisticated understanding of human action. Perner and Wimmer (1985) designed an interesting task to tap children's understanding of second-order belief. This task is based on the same paradigm that was used to investigate younger children's understanding of first-order false belief (Wimmer & Perner, 1983). They presented children with stories in which two actors, John and Mary, see an ice-cream van at the park where they are playing. Later, each is independently informed that the ice-cream van has moved from the park to the church, but neither knows that the other actor has been informed. In a series of six experiments, children between the ages of 5 and 10 were asked where John thinks Mary would go to buy an icecream. To respond correctly, children must take into account John's ignorance of Mary's knowledge of the true whereabouts of the ice-cream van. The findings across the individual experi-

It is currently estimated that about 30% of children with autism spectrum disorder remain minimally verbal, even after receiving years of interventions and a range of educational opportunities. Very little is known about the individuals at this end of the autism spectrum; in part because this is a highly variable population with no single set of defining characteristics or patterns of skills or deficits, and in part because it is extremely challenging to provide reliable or valid assessments of their developmental functioning. In this paper we summarize current knowledge based on research including minimally verbal children. We review promising new novel methods for assessing the verbal and nonverbal abilities of minimally verbal school-aged children, including eye-tracking and brain imaging methods that do not require overt responses. We then review what is known about interventions that may be effective in improving language and communication skills, including discussion of both non-augmentative and augmentative methods. In the final section of the paper we discuss the gaps in the literature and needs for future research.

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