Artificial intelligence (AI) is increasingly used in genomics research and practice, and generative AI has garnered significant recent attention. In clinical applications of generative AI, aspects of the underlying datasets can impact results, and confounders should be studied and mitigated. One example involves the facial expressions of people with genetic conditions. Stereotypically, Williams (WS) and Angelman (AS) syndromes are associated with a \"happy\" demeanor, including a smiling expression. Clinical geneticists may be more likely to identify these conditions in images of smiling individuals. To study the impact of facial expression, we analyzed publicly available facial images of approximately 3500 individuals with genetic conditions. Using a deep learning (DL) image classifier, we found that WS and AS images with non-smiling expressions had significantly lower prediction probabilities for the correct syndrome labels than those with smiling expressions. This was not seen for 22q11.2 deletion and Noonan syndromes, which are not associated with a smiling expression. To further explore the effect of facial expressions, we computationally altered the facial expressions for these images. We trained HyperStyle, a GAN-inversion technique compatible with StyleGAN2, to determine the vector representations of our images. Then, following the concept of InterfaceGAN, we edited these vectors to recreate the original images in a phenotypically accurate way but with a different facial expression. Through online surveys and an eye-tracking experiment, we examined how altered facial expressions affect the performance of human experts. We overall found that facial expression is associated with diagnostic accuracy variably in different genetic conditions.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

Individuals with autism spectrum disorders and those with Williams syndrome often have impairments in social behaviors. These two neurodevelopmental disorders are often reputed to be on the opposite ends of the social spectrum, with autistic individuals being socially avoidant and those with Williams syndrome highly social. Most research on children with autism and Williams syndrome has focused on preschool and younger school-age children. The current study assessed school-age children between the ages of 7-14 years with high-functioning autism, Williams syndrome, and neurotypical developing peers. Parents completed the Salk Institute Sociability Questionnaire and the Social Responsiveness Scale, to provide unique insights into social functioning and tap into different behavioral areas, social approach behaviors, and social responsiveness. This study provides additional evidence that young children with autism and Williams syndrome continue to show divergent social-behavioral tendencies at school-age, despite controlling for age and intellect. Results of this study better elucidate disparities as well as commonalities across school-age children with neurodevelopmental disorders and their typically developing peers, providing insight into everyday social functioning.

UNASSIGNED: The purpose of this study is to investigate the social and affective aspects of communication in school-age children with HFA and school-age children with WS using a micro-analytic approach. Social communication is important for success at home, school, work and in the community. Lacking the ability to effectively process and convey information can lead to deficits in social communication. Individuals with high functioning autism (HFA) and individuals with Williams syndrome (WS) often have significant impairments in social communication that impact their relationships with others. Currently, little is known about how school-age children use and integrate verbal and non-verbal behaviors in the context of a social interaction.
UNASSIGNED: A micro-analytic coding scheme was devised to reveal which channels children use to convey information. Language, eye gaze behaviors and facial expressions of the child were coded during this dyadic social interaction. These behaviors were coded throughout the entire interview, as well as when the child was the speaker and when the child was the listener.
UNASSIGNED: Language results continue to pose problems for the HFA and WS groups compared to their typically developing (TD) peers. For non-verbal communicative behaviors, a qualitative difference in the use of eye gaze was found between the HFA and WS groups. For facial expression, the WS and TD groups produced more facial expressions than the HFA group.
UNASSIGNED: No differences were observed in the HFA group when playing different roles in a conversation, suggesting they are not as sensitive to the social rules of a conversation as their peers. Insights from this study add knowledge toward understanding social-communicative development in school-age children.
UNASSIGNED: In this study, two non-verbal behaviors will be assessed in multiple contexts: the entire biographical interview, when the child is the speaker and when the child is the listener. These social and expressive measures give an indication of how expressive school-age children are and provide information on their attention, affective state and communication skills when conversing with an adult. Insights from this study will add knowledge toward understanding social-communicative development in school-age children.

Williams syndrome (WS) is a relatively rare genetic disorder. It arises from a microdeletion in chromosome 7q11.23, resulting in the loss of one copy of more than 20 genes. Disorders in multiple systems, including cardiovascular and nervous systems, occur in patients with WS. Here, we generated two human induced pluripotent stem cell (iPSC) lines from WS patients. Both lines expressed pluripotency markers at gene and protein levels. They possessed normal karyotypes and the potential to differentiate into three germ layers. They serve as a useful tool to study disease mechanism, test drugs, and identify promising therapeutics for patients with WS.

Cardiovascular system involvement is quite common and the leading cause of morbidity and mortality in patients with Williams syndrome (WS), most of whom need surgery. The present study aimed to provide a detailed evaluation of the features of surgical procedures and outcomes of patients with WS given as single-center experience, and additionally to make a detailed review from Türkiye.
Thirty-five children with WS diagnosed between the years 1992 and 2021 were evaluated retrospectively including cardiovascular data, surgical treatment features, and outcomes. A total of six articles from Türkiye were evaluated.
A total of 35 patients with Williams Syndrome (24 male) with a median age of cardiologic diagnosis of 6 months (range, 2 days-6 years) were evaluated. The cardiac defects of the patients with WS were found as supravalvular aortic stenosis (SVAS) (n=30, 85%) and peripheral pulmonary stenosis (PPS) (n=21, 65%). Additional cardiac anomalies were seen in 71% patients. The rate of SVAS and PPS surgery in all patients with WS was 77.1%. The median surgical age of the patients was 2.5 years (range, 7 months-15.5 years). No patients died due to surgery. But one patient died because of ventricular tachycardia due to anesthesia at the beginning of angiography. A total of 138 (63% male) patients with WS were evaluated from the articles published in Türkiye. Of 138 patients, 64.4% had SVAS, 52.1% had PPS, and 39.8% had additional cardiac anomaly. The median follow-up period ranged from 17 months to 18 years, and six (4.3%) patients died in the early postoperative period.
Cardiovascular system involvement is extremely common and is the leading cause of morbidity and mortality in patients with WS, often requiring surgical intervention. As seen in our study including 35 patients with WS and in publications from Türkiye, SVAS in patients with WS generally requires surgery, especially in the first year of life. PPS, on the other hand, requires surgery less frequently than SVAS, and pulmonary stenosis appears to decrease over time.

UNASSIGNED: Williams-Beuren syndrome (WBS) is a rare genetic disorder with delays in language and cognitive development, but, with increased awareness of clinical features and a reliable diagnostic test, WBS is becoming more widely recognized in childhood. Adaptive behavior skills and/or maladaptive behavior are important for the prognosis of individuals with WBS. The aim of this study was to investigate the clinical and developmental characteristics of patients with WBS and further increase awareness about it by evaluating the adaptive skills and maladaptive behaviors of the patients.
UNASSIGNED: The data of WBS patients followed-up at the Developmental Behavioral Pediatrics Unit were reviewed. Patient data on perinatal and postnatal history, developmental stages, physical and neurological examination findings were collected. The International Guide for Monitoring Child Development (GMCD) was administered to each child. In addition, semistructured interviews were conducted with the parents using the Vineland Adaptive Behavior Scales, Second edition (Vineland-II).
UNASSIGNED: A total of 12 patients diagnosed with WBS via detection of the 7q11.23 deletion, of whom 6 were girls, were retrospectively reviewed. The mean age at the time of review was 54.6 ± 32.5 months. The mean age at first presentation to the Developmental Behavioral Pediatrics Outpatient Clinic was 15 ± 11.5 months. In the first developmental evaluation using the GMCD, there was a delay in fine and gross motor domains in 6 patients, in the language domains in 4 patients, and in all of the domains in 2 patients. Findings with Vineland-II showed socialization and communication domains as strengths, but the daily living skills and motor skills domains were weaknesses. In terms of maladaptive behavior, the patients tended to frequently have behavioral problems, neurodevelopmental disease, anxiety disorders, eating problems, and sleeping problems.
UNASSIGNED: This retrospective review of 12 patients indicated a general delay in overall development, and confirmed impairment in both adaptive and maladaptive functioning in WBS.

Williams syndrome (WS) and Down syndrome (DS) are two neurodevelopmental disorders with distinct genetic origins characterized by mild to moderate intellectual disability. Individuals with WS or DS exhibit impaired hippocampus-dependent place learning and enhanced striatum-dependent spatial response learning. Here, we used the Weather Prediction Task (WPT), which can be solved using hippocampus- or striatum-dependent learning strategies, to determine whether individuals with WS or DS exhibit similar profiles outside the spatial domain. Only 10% of individuals with WS or DS solved the WPT. We further assessed whether a concurrent memory task could promote reliance on procedural learning to solve the WPT in individuals with WS but found that the concurrent task did not improve performance. To understand how the probabilistic cue-outcome associations influences WPT performance, and whether individuals with WS or DS can ignore distractors, we assessed performance using a visual learning task with differing reward contingencies, and a modified WPT with unpredictive cues. Both probabilistic feedback and distractors negatively impacted the performance of individuals with WS or DS. These findings are consistent with deficits in hippocampus-dependent learning and executive functions, and reveal the importance of congruent feedback and the minimization of distractors to optimize learning in these two populations.

Individuals with Williams syndrome (WS) may experience a variety of medical, behavioral, and educational concerns. The primary objective of this study was to assess barriers to health care for patients with WS, primarily using the Barriers to Care Questionnaire (BCQ), and to assess whether various demographic factors are correlated with these barriers. A REDCap survey was distributed using the Williams Syndrome Association Research Registry. 319 caregivers of individuals with WS in the United States completed the BCQ. On the BCQ, lower scores indicate more barriers to care. Younger age was associated with lower scores for both the pragmatics and the skills subscales while lower income levels and increased distances to providers knowledgeable about WS were consistently associated with lower total BCQ scores.

Understanding neurogenetic mechanisms underlying neuropsychiatric disorders such as schizophrenia and autism is complicated by their inherent clinical and genetic heterogeneity. Williams syndrome (WS), a rare neurodevelopmental condition in which both the genetic alteration (hemideletion of ~ twenty-six 7q11.23 genes) and the cognitive/behavioral profile are well-defined, offers an invaluable opportunity to delineate gene-brain-behavior relationships. People with WS are characterized by increased social drive, including particular interest in faces, together with hallmark difficulty in visuospatial processing. Prior work, primarily in adults with WS, has searched for neural correlates of these characteristics, with reports of altered fusiform gyrus function while viewing socioemotional stimuli such as faces, along with hypoactivation of the intraparietal sulcus during visuospatial processing. Here, we investigated neural function in children and adolescents with WS by using four separate fMRI paradigms, two that probe each of these two cognitive/behavioral domains. During the two visuospatial tasks, but not during the two face processing tasks, we found bilateral intraparietal sulcus hypoactivation in WS. In contrast, during both face processing tasks, but not during the visuospatial tasks, we found fusiform hyperactivation. These data not only demonstrate that previous findings in adults with WS are also present in childhood and adolescence, but also provide a clear example that genetic mechanisms can bias neural circuit function, thereby affecting behavioral traits.