591 - Neurodevelopmental Spectrum of a Cohort of Individuals with KBG Syndrome

Poster Number: 591
Publication Number: 591.1744

Background: KBG syndrome is a rare genetic condition caused by pathogenic variants in ANKRD11 or deletions on chromosome 16q involving ANKRD11. ANKRD11 encodes an ankyrin repeat domain-containing protein that plays a crucial role in neural development. It is clinically characterized by congenital anomalies, craniofacial dysmorphism, behavioral challenges, and developmental delay/intellectual disability. More than 150 cases have been reported, but this may be an underestimation as there is clinical variability, and features may be subtle or overlap with other conditions leading to misdiagnoses. Prospective studies evaluating the phenotypic spectrum of KBG syndrome are minimal.

Objective: The purpose of this study is to characterize the developmental and behavioral phenotypes of children with KBG syndrome.

Design/Methods: Participants with KBG syndrome were recruited from internal and local clinics. Inclusion criteria included informed consent, age of 5–17 years, and sufficient visual and motor abilities to complete the evaluations. Demographic information, and behavioral and developmental histories were collected. Cognitive abilities were assessed using the Differential Ability Scales-2nd Edition (DAS-II), and behaviors were assessed using the Behavior Assessment System for Children-3rd Edition (BASC-3) and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2).

Results: Four participants (1 F, 3 M) ages 6–13 years were enrolled. On the DAS-II, a basal was not reached for one participant. Individual cognitive profiles indicated that, for two of three participants, verbal scores were higher compared to spatial ability (p < 0.05), but there was no discrepancy between verbal and nonverbal scores. Nonverbal scores were also higher compared to spatial ability (p < 0.05) for two participants. For all three participants, the spatial cluster score was the lowest scoring domain. On the BASC-3, inattention was clinically significant for three participants and borderline at risk for one, and hyperactivity was clinically significant/at risk for three. The ADOS-2 overactivity code was elevated for all participants. Three participants had elevated scores on the social affect, and restricted and repetitive behavior (RRB) scales on the ADOS-2.

Conclusion(s): In KBG syndrome, cognitive abilities vary greatly, but symptoms of inattention and hyperactivity were seen in all participants, and RRB and deficits in social affect were seen in the majority. Results should be interpreted with caution due to the preliminary data set and small sample size. However, findings are consistent with current reports in the literature.