Presentation 24 – Dr Dejan Budimirovic

SSBP Virtual Symposium 2023

High Frequency of Neuropsychiatric Disorders and a Need for Treatment in Patients with FXAND Linked to FMR1 Gene Premutation Carriers

Presenting Author : Dr Dejan Budimirovic

Abstract

High Frequency of Neuropsychiatric Disorders and a Need for Treatment in Patients with FXAND Linked to FMR1 Gene Premutation Carriers

Budimirovic D. ^1,2

¹Kennedy Krieger Institute/ The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

²Department of Psychiatry & Behavioral Sciences-Child Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Background: Fragile X messenger ribonucleoprotein 1 (FMR1) gene premutation (PM) is linked to a higher frequency of anxiety, attention-deficit hyperactivity (ADHD), depression, autism spectrum disorder (ASD) and other Diagnostic Statistical Manual-5 (DSM-5) diagnosis under umbrella of fragile X-associated neuropsychiatric disorders (FXAND), which often requires treatments.

Methods: We examined for frequencies of FXAND and types of the treatments in a clinically ascertained cohort of 17 patients (76.5% paediatrics 8/13, 61.5% males; median age 12.0 yo) with PM (55-199 CGGs) from Fragile X Clinic at Kennedy Krieger Institute, approved by the Johns Hopkins’s Institutional Review Board.

Results: All patients had FXAND: anxiety and ADHD (70.6%), learning disabilities (52.9%) mostly in paediatrics, depression mostly in adults (29.4%), ASD (17.7%; all ≥ 100 CGGs), language disorders ( 17.6%). The study’s cohort mean number of CGG repeats was 82.50 ± 20.71. FMR1 gene protein (FMRP) level was 15.54 ± 10.84 pg/ng available for 29.4% of those patients. The vast majority (70.6%) of patients were on at least 1 psychotropic drug, SSRI were the most prescribed (47.1%). Non-drug treatments (41.2%) driven by paediatric patients had: 23.5% both speech-language and occupational, 17.6% behavioural, and 5.9% applied behavioural.

Conclusion: The clinical FMR1 PM cohort of both sexes had an extremely high frequency of FXAND: all had at least 1, 65% had 1-2 and 35% had 3-4 FXAND driven by anxiety and ADHD in 70% of the paediatric cases, slightly more affected were males. Depression was found in adults. The vast majority of them (71%) received psychotropic drug treatment, and 41% of them also had non-drug treatments driven by the paediatric population. The study contributes pilot data as for need to early diagnose and treat patients with the FMR1 gene PM-associated FXAND, to educate multispecialty clinicians, and to facilitate a such system-based interdisciplinary effort.

Keywords: FMR1 gene premutation, DSM-5 FXAND diagnosis, drug and non-drug treatments

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The Society for the Study of Behavioural Phenotypes (SSBP)

The Society for the Study of Behavioural Phenotypes (SSBP) is an international, interdisciplinary research society for studying the development, learning and behaviours of individuals with genetic disorders and ways of helping to improve lives. The society is registered as a charity in the UK (No. 1013849) and was set up in 1987.