Experience from a Pediatric Neurogenetics Multi-disciplinary Clinic: Neuropsychological Profiles of Patients with Chromosome 8p, STXBP1, SLC6A1, and Ring 14-related Encephalopathies
Abstract number :
3.365
Submission category :
11. Behavior/Neuropsychology/Language / 11B. Pediatrics
Year :
2022
Submission ID :
2205109
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Andrea Miele, PhD – Children's Hospital Colorado, University of Colorado School of Medicine; Kourtney Santucci, MD – Physician, Pediatrics/Special Care Clinic, Children's Hospital Colorado/University of Colorado School of Medicine; Katie Angione, MS – Genetic Counselor, Pediatrics/Child Neurology, Children's Hospital Colorado/University of Colorado School of Medicine; Kilby Mann, MD – Physician, Physical Medicine and Rehabilitation, Children's Hospital Colorado/University of Colorado School of Medicine; Tristen Dinkel, MSPC, BSN – Nurse Coordinator, Pediatrics/Child Neurology, Children's Hospital Colorado, University of Colorado School of Medicine; Lauren Treat, MD – Physician, Pediatrics/Child Neurology and Palliative Medicine, Children's Hospital Colorado, University of Colorado School of Medicine; Kristina Malik, MD – Physician, Pediatrics/Special Care Clinic, Children's Hospital Colorado, University of Colorado School of Medicine; Scott Demarest, MD – Physician, Pediatrics/Child Neurology, Children's Hospital Colorado, University of Colorado School of Medicine
Rationale: Developmental and Epileptic Encephalopathies are increasingly diagnosed given advances in genetic testing. However, detailed information about developmental profiles is lacking. More fine-tuned data about the distribution of intellectual abilities and language and motor skill development is integral to inform therapies and for family planning.
Methods: Children completed neuropsychological evaluations as part of their participation in Children’s Hospital Colorado’s Neurogenetics Clinic. A flexible assessment approach was critical given that ability levels were not necessarily predictable from age. Test selection included measures of infant development as well as IQ, expressive and receptive language, and visuomotor construction. Parents completed rating scales of social-emotional (BASC-3) and adaptive skills (Vineland-3).
Results: We report neuropsychological findings in 20 patients ages 0 y 6 m to 27 y 3 m: 9 with Chromosome 8p disorders, 3 with Ring 14 syndrome, 2 with pathogenic variants in SLC6A1, and 6 with pathogenic variants in STXBP1. About half (Figure 1; n=11) were only able to access measures intended for younger children. Of these 11 children, 8 had epilepsy (8p=2, Ring 14=2, STXBP1=4). On average, children with 8p demonstrated language and motor skills at a 12–36-month age equivalent, children with Ring 14 demonstrated skills at a 6-24-month age equivalent, and children with STXBP1 demonstrated skills at a 6-18-month age equivalent. Only 2 children had more than 5 words; most were nonverbal, though “happy” sounds were frequently heard. Diagnoses of Autism were present in nearly all children; other social-emotional difficulties also evident (BASC-3). Vineland scores were severely-to-profoundly impaired (ABC SS range=21-57, mean SS=32). A child with only a distal deletion on 8p demonstrated the least impaired scores.
The remaining children (Figure 2; n=9) were able to access age-appropriate measures. Five had epilepsy (Ring14=1, SLC6A1=2, STXBP1=2). Significant variability in cognitive performance was observed. Two children (8p Duplication only and pathogenic variant in STXBP1) demonstrated Average or better functioning. Another child with an 8p Deletion performed around the mild Intellectual Disability range (SS=57-79). Performance across the remaining 6 children fell in the profoundly impacted Intellectual Disability range (i.e., FSIQ below 70; range: 33-72). Vineland scores for this group were in the mild/moderately impaired range (ABC range: 52-68). Autism diagnoses and other social-emotional difficulties (BASC-3) were present in about half of the children._x000D_
Conclusions: The neurogenetic diagnoses of 8p, Ring14, SLC6A1, and STXBP1 confer significant risk of neurocognitive difficulties; however, specificity with regard to genetic syndrome and age at time of testing may provide additional information useful to predict cognitive performance over time. The findings reported here are limited by the small sample size. Continued follow-up will be important to track development over time especially in the face of seizure control and receipt of interventions.
Funding: This work is supported by Project 8P Foundation in conjunction with Ring14 USA, SLC6A1 Connect, and STXBP1 Disorders.
Behavior