Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers
<b>Background:</b> The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, <i>FMR1</i> gene) is associated with several conditions, including fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-asso...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/12/2399 |
| _version_ | 1797457760336478208 |
|---|---|
| author | Ramkumar Aishworiya Dragana Protic Si Jie Tang Andrea Schneider Flora Tassone Randi Hagerman |
| author_facet | Ramkumar Aishworiya Dragana Protic Si Jie Tang Andrea Schneider Flora Tassone Randi Hagerman |
| author_sort | Ramkumar Aishworiya |
| collection | DOAJ |
| description | <b>Background:</b> The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, <i>FMR1</i> 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. <b>Methods:</b> 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 <i>FMR1</i> 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. <b>Results:</b> 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, <i>p</i> < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, <i>p</i> = 0.002). <b>Conclusions:</b> 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. |
| first_indexed | 2024-03-09T16:27:35Z |
| format | Article |
| id | doaj.art-8e9d19259ecd4c5e85960962bd6964c9 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T16:27:35Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-8e9d19259ecd4c5e85960962bd6964c92023-11-24T15:06:20ZengMDPI AGGenes2073-44252022-12-011312239910.3390/genes13122399Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation CarriersRamkumar Aishworiya0Dragana Protic1Si Jie Tang2Andrea Schneider3Flora Tassone4Randi Hagerman5Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, 2825 50th Street, Sacramento, CA 95817, USADepartment of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pediatrics, School of Medicine, University of California Davis, 4610 X St, Sacramento, CA 95817, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, 2825 50th Street, Sacramento, CA 95817, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, 2825 50th Street, Sacramento, CA 95817, USAMedical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, 2825 50th Street, Sacramento, CA 95817, USA<b>Background:</b> The fragile X premutation carrier state (PM) (55–200 CGG repeats in the fragile X messenger ribonucleoprotein 1, <i>FMR1</i> 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. <b>Methods:</b> 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 <i>FMR1</i> 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. <b>Results:</b> 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, <i>p</i> < 0.001). Participants with ASD had a higher number of long-term medications compared to those without (2.32 vs. 1.3, <i>p</i> = 0.002). <b>Conclusions:</b> 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.https://www.mdpi.com/2073-4425/13/12/2399Fragile X premutationadolescentanxietyASDFSIQ<i>FMR1</i> |
| spellingShingle | Ramkumar Aishworiya Dragana Protic Si Jie Tang Andrea Schneider Flora Tassone Randi Hagerman Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers Genes Fragile X premutation adolescent anxiety ASD FSIQ <i>FMR1</i> |
| 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 | Fragile X premutation adolescent anxiety ASD FSIQ <i>FMR1</i> |
| url | https://www.mdpi.com/2073-4425/13/12/2399 |
| work_keys_str_mv | AT ramkumaraishworiya fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers AT draganaprotic fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers AT sijietang fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers AT andreaschneider fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers AT floratassone fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers AT randihagerman fragilexassociatedneuropsychiatricdisordersfxandinyoungfragilexpremutationcarriers |