Diminished social attention in pediatric brain tumor survivors: Using eye tracking technology during naturalistic social perception.

OBJECTIVE: The etiology of pediatric brain tumor survivor (PBTSs) social difficulties is not well understood. A model of social competence for youth with brain disorder and evidence from youth with autism spectrum disorder (ASD) suggests that diminished social attention may underlie social deficits in PBTSs. This study used eye tracking technology to compare visual social attention in PBTSs, youth with ASD, and typically developing (TD) youth. METHODS: Participants included 90 age-, gender-, and IQ-matched youth (N = 30 per group). PBTSs were at least 5 years from diagnosis and 2 years from the completion of tumor-directed therapy. Participants' eye gaze patterns were recorded while watching an established social play paradigm that presented videos of children engaging in either interactive or parallel play. Group differences in proportional gaze duration toward social versus nonsocial areas of interest were compared. Medical correlates of social attention in PBTSs were evaluated. RESULTS: Groups significantly differed in gaze preference across conditions, with PBTSs looking less at social areas of interest than TD youth and in a manner comparable to youth with ASD. Among PBTSs, multimodal tumor-directed therapy was associated with reduced gaze preference for faces. CONCLUSIONS: This study provides the first evidence of disrupted social attention in PBTSs, with parallels to the social attention deficits observed in ASD. Findings offer a new way to conceptualize the social difficulties of PBTSs and could guide interventions aimed at improving PBTS social adjustment by increasing visual attention to socially relevant information during social interactions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Clinical diagnosis of attention-deficit/hyperactivity disorder in survivors of pediatric brain tumors.

PURPOSE: Survivors of pediatric brain tumors often have neurodevelopmental late effects, such as inattention. Symptoms may mirror those of attention-deficit/hyperactivity disorder (ADHD), which affects ~ 5-8% of the general population. This retrospective study of survivors followed at a large tertiary care center examined the prevalence of a clinical diagnosis of ADHD, and risk factors associated with ADHD diagnosis and ADHD-related medication use. METHODS: A retrospective chart review of brain tumor survivors (n = 528), diagnosed between 2000 and 2015, who were at least 6 years old and 2 years from the end of tumor-directed therapy or from diagnosis, if no interventions were received. Clinical and demographic data were extracted from the medical record. RESULTS: Survivors were 55.7% male with mean age 8.15 ± 4.4 (0.0-16.0) years at brain tumor diagnosis. The most common diagnoses were low-grade glioma, medulloblastoma, and craniopharyngioma, with 52.5% of tumors supratentorial. Of the survivors, 81.3% received surgery, 40.0% radiation therapy, and 36.6% chemotherapy. Sixty-nine survivors (13.1%) had ADHD diagnoses, 105 (19.9%) had symptoms of ADHD without diagnoses, and 64 (12.1%) had ADHD medication use. ADHD diagnosis was associated with younger age at tumor diagnosis (p = 0.05) and supratentorial tumor location (p = 0.001). ADHD diagnosis was not associated with gender, tumor type, or treatment type. CONCLUSIONS: Survivors of brain tumors are at increased risk of ADHD and related symptoms. The greatest increase in risk occurs for survivors with diagnoses at younger ages and supratentorial tumors. Additional research is warranted, as select survivors may benefit from behavioral or pharmacologic ADHD treatments to optimize functioning.

Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly.

Holoprosencephaly (HPE), a common developmental forebrain malformation, is characterized by failure of the cerebrum to completely divide into left and right hemispheres. The etiology of HPE is heterogeneous and a number of environmental and genetic factors have been identified. Cytogenetically visible alterations occur in 25% to 45% of HPE patients and cytogenetic techniques have long been used to study copy number variants (CNVs) in this disorder. The karyotype approach initially demonstrated several recurrent chromosomal anomalies, which led to the identification of HPE-specific loci and, eventually, several major HPE genes. More recently, higher-resolution cytogenetic techniques such as subtelomeric multiplex ligation-dependent probe amplification and chromosomal microarray have been used to analyze chromosomal anomalies. By using chromosomal microarray, we sought to identify submicroscopic chromosomal deletions and duplications in patients with HPE. In an analysis of 222 individuals with HPE, a deletion or duplication was detected in 107 individuals. Of these 107 individuals, 23 (21%) had variants that were classified as pathogenic or likely pathogenic by board-certified medical geneticists. We identified multiple patients with deletions in established HPE loci as well as three patients with deletions encompassed by 6q12-q14.3, a CNV previously reported by Bendavid et al. In addition, we identified a new locus, 16p13.2 that warrants further investigation for HPE association. Incidentally, we also found a case of Potocki-Lupski syndrome, a case of Phelan-McDermid syndrome, and multiple cases of 22q11.2 deletion syndrome within our cohort. These data confirm the genetically heterogeneous nature of HPE, and also demonstrate clinical utility of chromosomal microarray in diagnosing patients affected by HPE.