Poster Session 10 Program Schedule
02/17/2024
09:00 am - 10:15 am
Room: Majestic Complex (Posters 61-120)
Poster Session 10: Neurodevelopmental | Congenital Conditions
Final Abstract #69
Neurobehavioral Patterns of Genotype-Phenotype Correlations in Individuals with Cornelia de Lange Syndrome
Rowena Ng, Kennedy Krieger Institute, Baltimore, United States
Julia O’Connor, Kennedy Krieger Institute, Baltimore, United States
Deirdre Summa, Cornelia de Lange Syndrome Foundation, Avon, United States
Antonie Kline, Greater Baltimore Medical Center, Baltimore, United States
Category: Genetics/Genetic Disorders
Keyword 1: genetic neuropsychology
Keyword 2: genetics
Keyword 3: pediatric neuropsychology
Objective:
Cornelia de Lange (CdLS) is a rare genetic disorder that affects multiple systems. Mutations in multiple genes including NIPBL and SMC1A, can cause the syndrome. To date, literature on genotype-phenotype associations in individuals with CdLS is extremely limited, although studies suggest differences in clinical phenotype severity across mutations. This study aimed to examine neurobehavioral differences and developmental variability across CdLS mutations, namely of NIPBL and SMC1A, and identify genotype-phenotype correlations.
Participants and Methods:
This patient-reported outcomes study included accessing data from the Coordination of Rare Diseases (CoRDS) registry at Sanford. A total of 26 parents of children/adults with a mutation in NIPBL (Mean age=20.46 years, SD=11.21) and 12 in SMC1A (Mean age=11.08 years, SD=9.04) completed a series of questionnaires regarding their child’s developmental history, including attainment of common language and motor milestones; intervention history; and behavior functioning. Developmental history and reported behavior regulation difficulties were compared across mutation groups.
Results:
Overall, individuals with a pathogenic variant in NIPBL or SMC1A were similarly delayed across motor and language milestones with about 70% not using phrase speech and 30-50% not walking by 5 years of age. However, those with NIPBL variants showed more severity in behavioral phenotype, namely with more repetitive behaviors, tantrums, and withdrawn behaviors. In addition, these individuals were more likely than those with SMC1A mutation to demonstrate self-injurious behaviors, and anxiety. Both groups yielded a similar proportion of participants who participated in speech and occupational, albeit it those with SMC1A variant were more likely to engage in physical therapy. Both clinical groups report low rate of communicative or assistive device use despite a large proportion of participants never mastering single word or sentence use.
Conclusions:
Study results are consistent with recent investigations highlighting more severe behavioral phenotype, particularly autistic features, anxiety, and behavior regulation challenges, among those with NIPBL mutation albeit comparable developmental milestones. Both groups endorsed very elevated attention problems. Findings highlight importance of early interventions, including behavioral health services.
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