Curtis K. Deutsch

Microduplications of 16p11.2 are associated with schizophrenia.

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 × 10−5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 × 10−7), bipolar disorder (P = 0.017) and autism (P = 1.9 × 10−7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 × 10−13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

Head circumference and height in autism : A study by the collaborative program of excellence in autism

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty‐eight probands with autism‐spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI‐R, ADOS‐G, DSM‐IV, and ICD‐10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non‐verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI‐R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research.

Validity and Reliability of Craniofacial Anthropometric Measurement of 3D Digital Photogrammetric Images

Background: Direct anthropometry performed during a patient examination is the standard technique for quantifying craniofacial dysmorphology, as well as for surgical planning and outcome assessment. Several new technologies have been designed to computerize anthropometric measurements, including three-dimensional (3D) digital photogrammetry. These digital systems have the advantage of acquiring patient craniofacial surface images quickly and noninvasively. Before morphometry using digital photogrammetry can be applied in clinical and research practice, it must be assessed against direct anthropometry. Objective: To evaluate the validity and reliability of facial anthropometric linear distances imaged by 3D digital photogrammetry with respect to direct anthropometry. Design, Setting, Participants, Measures: Standard craniofacial distances were directly measured twice on 20 normal adult volunteers. Craniofacial surfaces were also imaged using the 3dMDface digital photogrammetry system, and distances were digitally measured twice for each subject. Validity measures of accuracy and bias (for direct versus digital measurements) and reproducibility measures of precision and test-retest reliability (for repeated sets of digital measurements) were computed. Results: Seventeen of the 18 direct measurements correlated highly with digital values (mean r = 0.88). The correlation for one measurement (upper prolabial width) was not statistically significant. The overall precision of all 17 digital measurements was less than 1 mm, and the reliability was high (mean r = 0.91). Conclusions: Craniofacial anthropometry using the 3dMDface System is valid and reliable. Digital measurements of upper prolabial width may require direct marking, prior to imaging, to improve landmark identification.

Anthropometric proportions in the upper lip-lower lip-chin area of the lower face in young white adults☆

The relationships between measurements of the lower lip, chin, upper lip, and lower half and lower third of the face were studied. Fifteen new indices were formed with the help of eleven vertical linear, one horizontal linear, and two surface-arc measurements in the area. Neoclassic canons related to the lower face were not confirmed. On the average, the lower lip was 83% to 85% as large as the upper lip. The upper lip occupied one third of the lower face, while the lower lip occupied more than one third of the lower third of the face and the chin occupied the remainder. Skin covered 73.5% of the upper lip in males and 68% in females; it covered 63% of the lower lip in males and 61.1% in females. The remainder was covered by vermilion, more on the lower than on the upper lip and more protruding in females than in males. Proportion standards are a valuable contribution to the surface anatomy of the lower face of young white adults.

Brief report: cognitive correlates of enlarged head circumference in children with autism.

This study examined the frequency and cognitive correlates of enlarged head circumference in a sample of 63 children with autism between the ages of 4 and 14. Consistent with prior evidence, macrocephaly occurred at a significantly higher frequency than in a normal reference sample. Head circumference was not associated with language or executive functioning, nor was it related to verbal or nonverbal IQ. Head circumference was, however, correlated with discrepancies between verbal and nonverbal IQ scores, independent of absolute level of verbal ability. Children with discrepantly high nonverbal abilities had a mean standardized head circumference that was more than 1 SD greater than in the reference sample, and that was significantly greater than in autistic children with a relative verbal advantage or no discrepancy in cognitive abilities, for whom mean head circumference was within normal limits. This convergence of physical and cognitive features suggests a possible etiologically significant subtype of autism.

Objective assessment of standard nostril types. A morphometric study

Nostril type was assigned according to the inclination of the medial longitudinal axis of the nostrils, generally following the Topinard system in a group of randomly selected, healthy young North Americans. The group was composed of 156 Caucasians, 55 Asians, and 32 blacks. The 33 noses with asymmetrical nares were excluded from the remainder of the study. Five other measurements of the soft nose were taken (protrusion of the nasal lip, width of the nose, width of the columella, and length of the right and left columellar rims). Three indices showing the relationships of these measurements were also calculated. The most common nares were Type II in Caucasians (52.8%), Type III in Asians (52.8%), and Type VI in blacks (50.0%). Specific columellar and alar base configurations were associated with many nostril types. These data about nostril types and the soft nose provide important guidelines for reconstructive and cosmetric surgery.

Adjustment for Whole Brain and Cranial Size in Volumetric Brain Studies: A Review of Common Adjustment Factors and Statistical Methods

In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance, the proportion, and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations-chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes.

Genes and attention-deficit hyperactivity disorder

The initial molecular genetic studies of attention deficit hyperactivity disorder (ADHD) evaluated two candidate genes (DAT and DRD4) suggested by dopamine theories of this common disorder and its treatment with stimulant medication. The initial reports of weak associations with ADHD have been replicated by many (but not all) investigators, as is expected for genes with small effects. This literature is reviewed, along with emerging literature generated by active research groups investigating additional genes that might contribute to the genetic basis of this complex disorder.

Facial asymmetry in unilateral coronal synostosis: long-term results after fronto-orbital advancement.

Background: Unilateral coronal synostosis causes asymmetry of the forehead and face. The authors set out to document asymmetry and rotation of the middle/lower facial soft tissues using three-dimensional photogrammetry in adolescent and adult patients with unilateral coronal synostosis who underwent correction in infancy. Methods: All patients older than 10 years who had bilateral fronto-orbital advancement in infancy for nonsyndromic unilateral coronal synostosis were eligible for this study. The following paired anthropometric distances were measured: medial canthus to facial midline distance (endocanthion to sellion); middle facial depth (tragion to subnasale); and lower facial depth (tragion to gnathion). Nasal tip deviation (sellion to pronasale) and facial midline deviation (sellion to subnasale to gnathion) were also measured. Results: There were 15 patients with an average age at fronto-orbital advancement of 8 months (range, 3 to 14 months). Three-dimensional digital images were taken at an average age of 14 years (range, 11 to 29 years). Digital anthropometry documented decreased mean middle facial depth (5.1 ± 3.2 mm; p < 0.00001) and lower facial depth (2.7 ± 2.5 mm; p < 0.00001) on the fused side. Average deviation of the nasal tip and facial midline to the nonfused side was 5.0 ± 1.2 degrees and 3.4 ± 0.7 degrees, respectively. All 15 patients exhibited rotation of the middle and lower face to the nonfused side (chi-square analysis, p < 0.0001). Applying the Bonferroni correction, asymmetry did not correlate with age at frontal advancement or age at digital imaging. Conclusion: Adolescents and adults with unilateral coronal synostosis who underwent fronto-orbital advancement in infancy have consistent middle and lower facial asymmetry.

Attention deficits, Attention-Deficit Hyperactivity Disorder, and intellectual disabilities

Attention-Deficit Hyperactivity Disorder (ADHD) and its earlier nosologic classifications have been extensively investigated since the 1960s, with PubMed listings alone exceeding 13,000 entries. Strides have been made in the diagnosis and treatment of ADHD in individuals with intellectual function in the normal range, as described in companion reviews in this special issue. In contrast, comparatively little is known about ADHD in intellectual developmental disabilities (IDD) despite the possibility that ADHD is statistically overrepresented among individuals with IDD (Pearson et al. 1997 Attention-deficit/hyperactivity disorder in mental retardation: nature of attention deficits. In: Burack J, Enns J, editors. Attention, development, and psychopathology. New York: Guilford Press. p 205-229; Pearson et al. 2000 Am. J. Ment. Retard. 105:236-251). Here, we provide a review of diagnostic controversies in ADHD with IDD, and discuss several topics that are currently attracting research efforts in the field. These include behavioral phenotyping and attempts to come to grips with problems of behavioral and etiological heterogeneity. Additionally, we consider issues relating to methodologically sound assessment of attention disorders and evidence-based intervention procedures that may clarify and/or ameliorate attention deficits in individuals with IDD.