Paige M Siper1,2,3, Christina Layton1,2, Tess Levy1,2, Stacey Lurie1,4, Nurit Benrey1,4, Jessica Zweifach1,2, Mikaela Rowe5, Lara Tang6, Sylvia Guillory1,2, Danielle Halpern1,2, Ivy Giserman-Kiss7, Maria Del Pilar Trelles1,2,3, Jennifer H Foss-Feig1,2, Silvia De Rubeis1,2,3,8, Teresa Tavassoli9,10, Joseph D Buxbaum1,2,3,7,8,11, Alexander Kolevzon1,2,3,12. 1. Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 2. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 3. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 4. Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY 10461, USA. 5. Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA. 6. David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. 7. Neurodevelopmental and Behavioral Phenotyping Service, National Institutes of Mental Health, Bethesda, MD 20814, USA. 8. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 9. School of Psychology and Clinical Language Sciences, University of Reading, Berkshire RG6 6BZ, UK. 10. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 11. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 12. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Abstract
Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.
Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.
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Authors: Alexander Kolevzon; Tess Levy; Sarah Barkley; Sandra Bedrosian-Sermone; Matthew Davis; Jennifer Foss-Feig; Danielle Halpern; Katherine Keller; Ana Kostic; Christina Layton; Rebecca Lee; Bonnie Lerman; Matthew Might; Sven Sandin; Paige M Siper; Laura G Sloofman; Hannah Walker; Jessica Zweifach; Joseph D Buxbaum Journal: HGG Adv Date: 2022-08-27