Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

The Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000) is widely accepted as a "gold standard" diagnostic instrument, but it is of restricted utility with very young children. The purpose of the current project was to modify the ADOS for use in children under 30 months of age. A modified ADOS, the ADOS Toddler Module (or Module T), was used in 360 evaluations. Participants included 182 children with best estimate diagnoses of ASD, non-spectrum developmental delay or typical development. A final set of protocol and algorithm items was selected based on their ability to discriminate the diagnostic groups. The traditional algorithm "cutoffs" approach yielded high sensitivity and specificity, and a new range of concern approach was proposed.Keywords autism spectrum disorders; diagnosis; ADOS; infants; toddlers Almost ten years ago, the standardization of a revised Autism Diagnostic Observation Schedule (ADOS), a semi-structured assessment for the diagnosis of autism spectrum disorders (ASD) (Lord, Rutter, DiLavore & Risi, 1999) was described. The ADOS has gradually become an integral part of many research and clinical protocols of children suspected of having an autism spectrum disorder (ASD). Due to the growing understanding of symptoms in the first two years of life and the desire of researchers and clinicians to have standardized instruments for use with infants and young toddlers, there is a need for diagnostic tools that are appropriate for very young children. This paper presents a new Toddler Module of the ADOS. The Toddler Module retains the original spirit and many of the original tasks of the ADOS, but is intended for use in children under 30 months of age who have nonverbal mental ages of at least 12 months. The scope of this report is to provide a summary of the new measure, the procedures used to develop it, a description of the standardization sample and relevant psychometrics.In introducing this new module, it is valuable to review the structure of the previously published ADOS. The ADOS evaluates social interaction, communication and play through a series of planned "presses" (Lord et al., 1989) in the context of a naturalistic social interaction. Some of the presses are intended to offer a high level of structure for the participant, while others are intended to provide less structure. All presses, however, afford contexts for both initiations and responses, which are then coded in a standardized manner. An algorithm, which sums the scores of particular items from the measure, yields a classification indicative of autism, ASD or nonspectrum conditions. This classification can then be used by a clinician or researcher as one part of a comprehensive diagnostic process.The first ADOS was introduced in the late 1980s and was intended for children who had a spoken language age equivalent of at least 36 months. A revision was published in 2000 that reflected the need for the measure to be applicable to a wider range of chronological and developmental ages. The 2000 version provided f...

OBJECTIVES: To compare the effects of two 9-month parent-implemented interventions within the Early Social Interaction (ESI) Project. Both individual-ESI, offered 2 or 3 times per week at home or in the community, and group-ESI, offered once per week in a clinic, taught parents how to embed strategies to support social communication throughout everyday activities. METHODS: Participants in the randomized controlled trial included 82 children diagnosed with autism spectrum disorder at 16 to 20 months. Children were matched on pretreatment nonverbal developmental level and pairs were randomly assigned to treatment condition. Child outcomes included measures of social communication, autism symptoms, adaptive behavior, and developmental level. Child outcomes are reported from baseline to the end of the 9-month interventions. RESULTS: Children in individual-ESI showed differential change on a standardized examiner-administered observational measure of social communication, as they improved at a faster rate than children in group-ESI. Individual-ESI also showed differential efficacy on a parent report measure of communication, daily living, and social skills, as they showed improvement or stability, whereas group-ESI led to worsening or no significant change on these skills. Finally, individual-ESI showed differential change on examiner-administered measures of receptive language skills, as children in individual-ESI improved significantly, whereas group-ESI showed no change. CONCLUSIONS: These findings support the efficacy of individual-ESI compared with group-ESI on child outcomes, suggesting the importance of individualized parent coaching in natural environments. The efficacy of a parent-implemented intervention using little professional time has potential for community viability, which is particularly important in light of the lack of main effects on child outcomes of most other parent-implemented interventions.

BACKGROUND: Universal screening is recommended to reduce the age of diagnosis for autism spectrum disorder (ASD). However, there are insufficient data on children who screen negative and no study of outcomes from truly universal screening. With this study, we filled these gaps by examining the accuracy of universal screening with systematic follow-up through 4 to 8 years. METHODS: Universal, primary care-based screening was conducted using the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F) and supported by electronic administration and integration into electronic health records. All children with a well-child visit (1) between 16 and 26 months, (2) at a Children's Hospital of Philadelphia site after universal electronic screening was initiated, and (3) between January 2011 and July 2015 were included (N = 25 999). RESULTS: Nearly universal screening was achieved (91%), and ASD prevalence was 2.2%. Overall, the M-CHAT/F's sensitivity was 38.8%, and its positive predictive value (PPV) was 14.6%. Sensitivity was higher in older toddlers and with repeated screenings, whereas PPV was lower in girls. Finally, the M-CHAT/F's specificity and PPV were lower in children of color and those from lower-income households. CONCLUSIONS: Universal screening in primary care is possible when supported by electronic administration. In this "real-world" cohort that was systematically followed, the M-CHAT/F was less accurate in detecting ASD than in previous studies. Disparities in screening rates and accuracy were evident in traditionally underrepresented groups. Future research should focus on the development of new methods that detect a greater proportion of children with ASD and reduce disparities in the screening process. WHAT'S KNOWN ON THIS SUBJECT: Universal screening for autism spectrum disorder is recommended in primary care to facilitate early detection. However, the US Preventive Services Task Force concluded that there is currently insufficient data from primary care and with longitudinal follow-up to recommend universal screening. WHAT THIS STUDY ADDS: We examined the accuracy of autism screening in a diverse cohort screened nearly universally (91%) and followed-up systematically. The M-CHAT/F had lower sensitivity and positive predictive value than in previous studies; disparities were observed in screening rates and accuracy.