INS NYC 2024 Program

Poster	Poster Session 08 Program Schedule 02/16/2024 01:45 pm - 03:00 pm Room: Shubert Complex (Posters 1-60) Poster Session 08: Cognition \| Cognitive Reserve Variables Final Abstract #56 The Neuropsychological Profile of an 11-Year-Old Female with a Pathogenic Variant of the GRIA2 Gene Katherine Paltell, University of Chicago Medicine, Chicago, United States Mary Lee, University of Chicago Medicine, Chicago, United States Yangfeifei Gao, University of Chicago Medicine, Chicago, United States Category: Genetics/Genetic Disorders Keyword 1: genetic disorders Keyword 2: autism spectrum disorder Keyword 3: pediatric neuropsychology Objective: Pathogenic variant of the glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) gene is a rare mutation found in approximately 25-30 individuals worldwide. GRIA2 variants are reported to cause both loss and gain-of-function in glutamate receptor (GluA2) subunits of ligand-gated cation channels, resulting in disruptions in glutamatergic synaptic transmission. An increasing number of case studies have documented highly heterogeneous clinical manifestations of GRIA2 variants, including developmental delays, intellectual disability, autism spectrum disorder (ASD), behavioral challenges, and epilepsy. However, research on neuropsychological findings is limited. The present case illustrates the complexity of neuropsychological profile and behavioral findings of this rare genetic condition. Participants and Methods: The patient is an 11-year-old White female with a history of ASD, attention-deficit/hyperactivity disorder, and developmental articulation disorder, for which she received extensive interventions. She also has drug-resistant focal epilepsy (onset at 8 years of age) with one episode of status epilepticus of unknown duration. Seizure semiology and EEG findings suggest right mesial temporal lobe origin. Her seizures are triggered almost exclusively by showers or baths. Genetic testing revealed a pathogenic gain-of-function variant of the GRIA2 gene associated with increased sensitivity to glutamate. Referral concerns pertained to a progressive worsening of cognitive, emotional, and behavioral functioning following seizure onset. Standardized measures of intellectual ability, language, and reading skills were administered as part of the evaluation, in addition to the Autism Diagnostic Observation Schedule (ADOS-2). Results: The patient’s broad cognitive abilities were in the exceptionally low range. In line with her history of extensive speech therapy, a relative strength in verbal abilities emerged with low average to average abstract verbal reasoning, single-word expressive and receptive vocabulary, and single-word reading performances. On the ADOS-2, she demonstrated a high level of social communication and interaction difficulties consistent with ASD. She was highly socially motivated and made many social overtures. However, these were poorly integrated and often inappropriate to the context. Behavioral concerns noted by parents were also observed during testing, including impulsivity, hyperactivity, and behavioral dysregulation. She engaged in consistent and repetitive skin picking until the point of bleeding. She became physically aggressive with other patients in the waiting room, attempted to elope from the testing room, and required behavioral management and physical redirection. Conclusions: This case study contributes to the emerging characterization of phenotypes of pathogenic gain-of-function GRIA2 gene variants in relation to neurodevelopment and medical outcomes. Our findings accord with prior case studies demonstrating associations between GRIA2 variants and neurodevelopmental disorders, seizures, and behavioral abnormalities. Our patient’s verbal abilities reflect a unique area of strength relative to other documented cases of GRIA2 variants, among which verbal abilities were often profoundly impaired. Additional research is warranted to better understand neuropsychological outcomes in this population.

Poster

02/16/2024
01:45 pm - 03:00 pm
Room: Shubert Complex (Posters 1-60)

Poster Session 08: Cognition | Cognitive Reserve Variables

Final Abstract #56

The Neuropsychological Profile of an 11-Year-Old Female with a Pathogenic Variant of the GRIA2 Gene

Katherine Paltell, University of Chicago Medicine, Chicago, United States
Mary Lee, University of Chicago Medicine, Chicago, United States
Yangfeifei Gao, University of Chicago Medicine, Chicago, United States

Category: Genetics/Genetic Disorders

Keyword 1: genetic disorders
Keyword 2: autism spectrum disorder
Keyword 3: pediatric neuropsychology

Objective:

Pathogenic variant of the glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) gene is a rare mutation found in approximately 25-30 individuals worldwide. GRIA2 variants are reported to cause both loss and gain-of-function in glutamate receptor (GluA2) subunits of ligand-gated cation channels, resulting in disruptions in glutamatergic synaptic transmission. An increasing number of case studies have documented highly heterogeneous clinical manifestations of GRIA2 variants, including developmental delays, intellectual disability, autism spectrum disorder (ASD), behavioral challenges, and epilepsy. However, research on neuropsychological findings is limited. The present case illustrates the complexity of neuropsychological profile and behavioral findings of this rare genetic condition.

Participants and Methods:

The patient is an 11-year-old White female with a history of ASD, attention-deficit/hyperactivity disorder, and developmental articulation disorder, for which she received extensive interventions. She also has drug-resistant focal epilepsy (onset at 8 years of age) with one episode of status epilepticus of unknown duration. Seizure semiology and EEG findings suggest right mesial temporal lobe origin. Her seizures are triggered almost exclusively by showers or baths. Genetic testing revealed a pathogenic gain-of-function variant of the GRIA2 gene associated with increased sensitivity to glutamate. Referral concerns pertained to a progressive worsening of cognitive, emotional, and behavioral functioning following seizure onset. Standardized measures of intellectual ability, language, and reading skills were administered as part of the evaluation, in addition to the Autism Diagnostic Observation Schedule (ADOS-2).

Results:

The patient’s broad cognitive abilities were in the exceptionally low range. In line with her history of extensive speech therapy, a relative strength in verbal abilities emerged with low average to average abstract verbal reasoning, single-word expressive and receptive vocabulary, and single-word reading performances. On the ADOS-2, she demonstrated a high level of social communication and interaction difficulties consistent with ASD. She was highly socially motivated and made many social overtures. However, these were poorly integrated and often inappropriate to the context. Behavioral concerns noted by parents were also observed during testing, including impulsivity, hyperactivity, and behavioral dysregulation. She engaged in consistent and repetitive skin picking until the point of bleeding. She became physically aggressive with other patients in the waiting room, attempted to elope from the testing room, and required behavioral management and physical redirection.

Conclusions:

This case study contributes to the emerging characterization of phenotypes of pathogenic gain-of-function GRIA2 gene variants in relation to neurodevelopment and medical outcomes. Our findings accord with prior case studies demonstrating associations between GRIA2 variants and neurodevelopmental disorders, seizures, and behavioral abnormalities. Our patient’s verbal abilities reflect a unique area of strength relative to other documented cases of GRIA2 variants, among which verbal abilities were often profoundly impaired. Additional research is warranted to better understand neuropsychological outcomes in this population.