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Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers

Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with cur...

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Autores principales: Aishworiya, Ramkumar, Protic, Dragana, Tang, Si Jie, Schneider, Andrea, Tassone, Flora, Hagerman, Randi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778214/
https://www.ncbi.nlm.nih.gov/pubmed/36553666
http://dx.doi.org/10.3390/genes13122399
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author Aishworiya, Ramkumar
Protic, Dragana
Tang, Si Jie
Schneider, Andrea
Tassone, Flora
Hagerman, Randi
author_facet Aishworiya, Ramkumar
Protic, Dragana
Tang, Si Jie
Schneider, Andrea
Tassone, Flora
Hagerman, Randi
author_sort Aishworiya, Ramkumar
collection PubMed
description Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals.
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spelling pubmed-97782142022-12-23 Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers Aishworiya, Ramkumar Protic, Dragana Tang, Si Jie Schneider, Andrea Tassone, Flora Hagerman, Randi Genes (Basel) Article Background: The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, FMR1 gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor ataxia (FXTAS), with current literature largely primarily investigating older PM individuals. The aim of this study was to identify the prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young PM individuals. Methods: This was a retrospective study conducted through a medical record review of PM individuals who were seen either for clinical concerns (probands, 45.9%) or identified through the cascade testing (non-probands, 54.1%) of an affected sibling with fragile X syndrome. Information on the presence of autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, long-term psychiatric medication intake, and cognitive function, based on standardized assessments, was obtained. Molecular data, including CGG repeat number and FMR1 mRNA levels, were also available for a subset of participants. Analysis included descriptive statistics and a test of comparison to describe the clinical profile of PM individuals pertinent to FXAND. Results: Participants included 61 individuals (52 males and 9 females) aged 7.8 to 20.0 years (mean 12.6 ± 3.4) with a mean full-scale IQ of 90.9 ± 22.7. The majority (N = 52; 85.2%) had at least one mental health disorder, with anxiety being the most common (82.0% of subjects), followed by ADHD (66.5%), and ASD (32.8%). Twenty-seven (87.1%) of non-probands also had at least one mental health condition, with probands having lower cognitive and adaptive skills than non-probands. ASD was present in 20 participants (17/52 males and 3/9 females; 15 probands) with significantly lower FSIQ in those with ASD (mean 73.5 vs. 98.0, p < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, p = 0.002). Conclusions: Our findings indicate a high rate of FXAND diagnoses within a cohort of young PM individuals, including those identified via cascade testing, although this was not a population sample. An awareness of the entity of FXAND and the early recognition of the symptoms of associated conditions may facilitate timely and appropriate care for PM individuals. MDPI 2022-12-17 /pmc/articles/PMC9778214/ /pubmed/36553666 http://dx.doi.org/10.3390/genes13122399 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aishworiya, Ramkumar
Protic, Dragana
Tang, Si Jie
Schneider, Andrea
Tassone, Flora
Hagerman, Randi
Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title_full Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title_fullStr Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title_full_unstemmed Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title_short Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
title_sort fragile x-associated neuropsychiatric disorders (fxand) in young fragile x premutation carriers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778214/
https://www.ncbi.nlm.nih.gov/pubmed/36553666
http://dx.doi.org/10.3390/genes13122399
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