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