Early Developmental Sequelae and Neurobiological Phenotype of Patient With 1q24.2q44 Trisomy

Partial trisomy of chromosome 1q is exceedingly rare, with few reported cases surviving past infancy. We present a prospective longitudinal case of partial mosaic trisomy 1q24.2q44 with co-occurring autism spectrum disorder (ASD). In addition to the chromosomal abnormality, the case study patient (herein, “CS”) had a first-degree relative with ASD, representing dual genetic liability. CS’s profile is distinguished from other 1q trisomies by phenotype, clinical course, and attentional brain responses. This case offers rare insight into developmental trajectories and clinical implications for individuals with 1q trisomy. CS’s 3-year-long developmental profile consisted of increasing global developmental delays, progressive ASD features, and cerebral palsy. Mild language regression occurred between 2 and 3 years. Neurobiological assessment of attention at age 2 years revealed large autistic-like attention response patterns, suggestive of delayed cognition, a pattern associated with neurocognitive deficits observed in ASD. Unlike prior reports of trisomy 1q, CS demonstrated relative strengths in behavioral regulation skills in the absence of inattention, impulsivity, and seizures. Early intervention, initiated between 6 and 9 months, likely supported development of motor and regulation skills. Global delays were most plausibly attributable to her chromosomal abnormality, while family history of ASD suggests that shared, unidentified variants conferred additional risk. Notably, genetic testing was delayed until 9 months of age, despite an actionable congenital finding (triphalangeal thumb) that could have prompted earlier intervention. Following recent Council on Genetics recommendations, phenotypic and agnostic testing approaches can ensure timely diagnosis, guide prognostication, enable surveillance for disorder-related complications, and inform targeted interventions.