There is significant heterogeneity in clinical presentations, brain-imaging findings, and genetic underpinnings of autism. Autism traits, particularly social affect and joint attention, and related domains of adaptive functioning and cognitive development, are key characteristics in determining autism “profiles”. This study aimed to understand such baseline profiles in preschool autistic children receiving early intervention (age range, 2–7 years old; sample size N = 67). We also examined the association between phenotypic pre-intervention characteristics and response to intervention using Early Start Denver Model (ESDM). Baseline characteristics prior to receiving early intervention demonstrated a link between eye tracking measure of joint attention, namely better gaze accuracy, and clinical profile of autism traits, particularly better social affect/social overtures and adaptive functioning. Further, better receptive and expressive language, visual reception and fine motor skills, and higher development quotients on a visual processing task, were found to be associated with more accurate eye movements on a joint attention task. Predictors of improvement in autistic traits post-intervention included higher age at entry to intervention and baseline developmental functioning. Specifically, social affect was found to change in the same direction as cognitive functioning post-ESDM intervention, especially with regard to visual reception, fine motor and receptive language skills. The findings also suggest that better social affect and joint attention, characterised by better social overtures and maintenance of attention, are predictive of more accurate eye gaze in a social exercise, thereby making these potential intervention targets in early intervention.
Sensory differences constitute core diagnostic features of autism. The cascading effect model posits that early sensory differences may be prospectively associated with subsequent autistic traits, whereas empirical evidence in infancy remains scarce. This study aims to characterize trajectory differences of early sensory profiles and examine the cascading effect on subsequent autistic traits in infants later diagnosed with autism. In this prospective longitudinal study, 134 Chinese infants were followed from 12 to 36 months of age. Trajectory differences in four sensory profiles (sensitivity, avoiding, registration, and seeking) were compared between diagnostic groups using the Toddler Sensory Profile-2. The cascading effect were examined through Structural Equation Modeling and temporally ordered path analysis to test direct and indirect effects of early sensory differences on subsequent autistic traits via the mediation of social skills in autism. Compared to typical development, infants later diagnosed with autism exhibited significantly elevated sensory sensitivity and sensory avoiding, along with elevated sensory registration scores at 12 months, with sensory sensitivity showing differential trajectories over time (F = 3.25, p = 0.004). Elevated sensory avoiding at 18 months exerted an indirect effect on social-communication at 36 months via the mediating role of social skills at 24 months (B = 0.08, p = 0.007). Additionally, temporally ordered path analysis revealed that elevated sensory avoiding at 18 months negatively predicted social skills at 24 months (β = -0.19, p = 0.030). Notably, in an exploratory analysis, increased sensory seeking at 18 months positively predicted adaptive skills at 36 months (B = 0.97, p = 0.031). Sensory differences emerge as early as 12 months in infants who later receive an autistic diagnosis, with sensory sensitivity demonstrating distinct developmental trajectories. These findings provide prospective evidence to support the cascading effect model in autism, identifying early sensory avoiding as an important early correlate of subsequent social-communicative development. Furthermore, early sensory seeking behaviors may facilitate subsequent adaptive functioning, highlighting the heterogeneous developmental pathways within autism. www.chictr.org.cn; Trial No: ChiCTR2100049811; Trial Date:2021.08.10.
Establishing evidence of content validity, or how well a measure reflects the intended outcome, is essential for developing or selecting assessment tools that support individualized care and research in clinical populations like Down syndrome (DS). This study aimed to examine caregiver-reported relevance of a widely used measure of executive function in school-aged youth with DS, the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Parent Form. Specifically, this study focused on one aspect of content validity, relevance to the target population, which has yet to be systematically evaluated in DS. This study integrated data from two online studies of youth with DS. After completing the BRIEF-2, caregivers were asked forced-choice questions about the relevance of the measure to their child with DS, as well as an open-text question about their response strategy for items they deemed not relevant. Caregivers of 281 youth with DS between the ages of 6–18 years (M = 12.7, SD = 3.4) reported on the relevance of the BRIEF-2 for their child. Just under half (46.3
BACKGROUND:Heterozygous variants in FBXW7 have recently been recognized as a cause of a rare neurodevelopmental disorder with variable developmental delay, neurological manifestations, and multisystem involvement. The breadth of clinical variability and penetrance remains incompletely defined. CASES PRESENTATION:We report a retrospective multicenter case series of seven previously unreported individuals (five males, two females) with heterozygous FBXW7 variants identified through clinical genetic testing, aged 5-9 years at last evaluation (median 6 years). Six variants occurred de novo and one was inherited. Neurodevelopmental involvement was present in six individuals and was characterized by global developmental delay and language impairment; hypotonia was observed in all seven. Formal intellectual disability was documented in four cases, while one individual showed preserved cognitive functioning with predominant behavioral difficulties. Epileptic seizures occurred in four individuals, whereas three had no history of epilepsy. Brain MRI was available for six individuals and was normal in four, whereas two showed structural anomalies involving the corpus callosum. Extracerebral features were variably reported, most commonly constipation and recurrent respiratory/otolaryngological infections. Comparison with previously reported individuals confirmed the core neurodevelopmental phenotype and further refined the spectrum. CONCLUSIONS:This case series expands the phenotypic spectrum associated with FBXW7-related neurodevelopmental disorder and highlights variable expressivity and incomplete penetrance, including clinically relevant variants presenting with mild or atypical phenotypes. These findings support considering FBXW7 across a broad range of neurodevelopmental presentations and inform genetic counseling.
Cerebral palsy (CP) is a neurodevelopmental disorder with a significant male predisposition, yet the underlying genetic mechanisms driving this sex-specific risk remain poorly understood. Given the hemizygous state of X-linked variants in males, we hypothesized that X-chromosomal genetic variations may contribute to CP susceptibility in male patients. We performed an X-chromosome-wide association study (XWAS) using whole-exome sequencing (WES) data from 1,076 male CP patients and 1,057 healthy male controls of Chinese ancestry. Quality control, principal component analysis (PCA), and logistic regression were applied to identify risk loci for CP. Six candidate single nucleotide variants (SNVs) in UTP14A were genotyped via MassARRAY, and haplotype analysis was conducted using SHEsis. We identified a significant association between the intronic variant rs2281277 in UTP14A and CP (P = 1.38E-05, FDR q-value = 0.0465, OR = 0.644). In addition to the lead SNV rs2281277, five other SNVs in UTP14A also showed a suggestive association with CP, including rs141750783, rs61318448, rs2273021, rs2281278, and rs111975985. Haplotype analysis further revealed a risk haplotype (CGTATC) defined by these six SNVs, which was associated with a 53.1
