The fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder seen in older premutation (55–200 CGG repeats) carriers of FMR1. The premutation has excessive levels of FMR1 mRNA that lead to toxicity and mitochondrial dysfunction. The clinical features usually begin in the 60 s with an action or intention tremor followed by cerebellar ataxia, although 20% have only ataxia. MRI features include brain atrophy and white matter disease, especially in the middle cerebellar peduncles, periventricular areas, and splenium of the corpus callosum. Neurocognitive problems include memory and executive function deficits, although 50% of males can develop dementia. Females can be less affected by FXTAS because of a second X chromosome that does not carry the premutation. Approximately 40% of males and 16% of female carriers develop FXTAS. Since the premutation can occur in less than 1 in 200 women and 1 in 400 men, the FXTAS diagnosis should be considered in patients that present with tremor, ataxia, parkinsonian symptoms, neuropathy, and psychiatric problems. If a family history of a fragile X mutation is known, then FMR1 DNA testing is essential in patients with these symptoms.

Fragile X-associated tremor and ataxia syndrome (FXTAS) is a neurodegenerative disease developed by carriers of a premutation in the fragile X mental retardation 1 (FMR1) gene. The core clinical symptoms usually manifest in the early 60s, typically beginning with intention tremor followed by cerebellar ataxia. Ataxia can be the only symptom in approximately 20% of the patients. FXTAS has a slow progression, and patients usually experience advanced deterioration 15 to 25 years after the initial diagnosis. Common findings in brain imaging include substantial brain atrophy and white matter disease (WMD). We report three cases with an atypical clinical presentation, all presenting with gait problems as their initial manifestation and with ataxia as the dominant symptom without significant tremor, as well as a faster than usual clinical progression. Magnetic resonance imaging (MRI) was remarkable for severe brain atrophy, ventriculomegaly, thinning of the corpus callosum, and periventricular WMD. Two cases were diagnosed with definite FXTAS on the basis of clinical and radiological findings, with one individual also developing moderate dementia. Factors such as environmental exposure and general anesthesia could have contributed to their clinical deterioration. FXTAS should be considered in the differential diagnosis of patients presenting with ataxia, even in the absence of tremor, and FMR1 DNA testing should be sought in those with a family history of fragile X syndrome or premutation disorders.

Background: While an association between full mutation CGG-repeat expansions of the Fragile X Mental Retardation 1 (FMR1) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55–200 repeats) of the FMR1 gene may be overlooked. Objective: To report five FMR1 fXPCs cases with the hypermobile Ehlers-Danlos syndrome (hEDS) phenotype. Methods: We collected medical histories and FMR1 molecular measures from five cases who presented with joint hypermobility and loose connective tissue and met inclusion criteria for hEDS. Results: Five cases were female and ranged between 16 and 49 years. The range of CGG-repeat allele sizes ranged from 66 to 150 repeats. All had symptoms of hEDS since early childhood. Commonalities in molecular pathogenesis and coexisting conditions between the fXPCs and hEDS are also presented. The premutation can lead to a reduction of fragile X mental retardation protein, which is crucial in maintaining functions of the extracellular matrix-related proteins, particularly matrix metallopeptidase 9 and elastin. Moreover, elevated FMR1 messenger RNA causes sequestration of proteins, which results in RNA toxicity. Conclusion: Both hEDS phenotype and premutation involvement may co-occur because of related commonalities in pathogenesis.

Objective: To evaluate the effectiveness of parenting training on emotional and behavioral problems of first through fourth grade Thai children with ADHD compared with routine clinical care in a university hospital in southern Thailand. Material and methods: Caregivers of the children were invited and assessed for eligibility. Eighty children with ADHD were randomly assigned to either a parenting training group or a routine clinical care group. The primary caregivers of the parenting training group participated in 6 120-minute weekly sessions in addition to routine clinical care. Caregiver and teacher ADHD ratings and oppositional-defiant disorder ratings were collected at the time of enrollment and after the 6 weeks of training in both groups. The differences in scores in both groups were analyzed using a mixed model ANOVA. Results: Each arm had 40 participants. The mean (SD) age of the children was 8.3 (1.1) years and their mean (SD) age at the first diagnosis of ADHD was 6.8 (1.3) years. Most of them were receiving methylphenidate for treatment of their ADHD. The mother was the primary caregiver for 83.5% of the children. The ADHD symptoms and oppositional-defiant symptoms showed significant improvement after receiving the treatment in both groups; however, no significant differences were found between groups. Conclusion: Adding parenting training to the routine clinical care for children with uncomplicated ADHD who are being medicated was not more effective than the routine clinical care alone. However, the power of this study is limited, and follow-up is needed to evaluate the long-term effectiveness.

Background/Objectives: Disorders of gut–brain interaction (DGBI) include a spectrum of disorders with chronic/recurrent gastrointestinal symptoms, caused by dysregulation of microbiota–gut–brain interaction. Early-life events have been suggested as the main factors influencing the microbiota–gut–brain axis. We aimed to evaluate the prevalence of DGBI in 3-year-old children and its relationship with early-life events. Methods: The parents of children aged 3 years, who had been followed up in a well-baby clinic since they were 2 months old, were asked about any GI symptoms their child had experienced during the check-up visits between September 2023 and June 2024. The final diagnosis of DGBI was based on ROME IV criteria. Demographic data, including early-life factors, were collected. Results: Overall, 568 children (48.6% boys) were included, of whom 139 (24.5%) had symptoms consistent with at least one DGBI diagnosis. The most prevalent DGBI was functional constipation (20.4%), followed by colic (4.6%), infant regurgitation (2.8%), and dyschezia (1.6%). Approximately 48% of the children were breastfed for ≥6 months, and 21% were exposed to ≥1 antibiotic/antiviral drugs in the first year of life. DGBI prevalence was significantly higher in girls than in boys (28.1% vs. 20.7%; p = 0.041). Exclusive breastfeeding was the most significant protective factor against DGBI, particularly if performed for ≥3 months. Conclusions: Sex was the most significant factor affecting DGBI prevalence in children aged ≤3 years; breastfeeding offers the most effective protection against DGBI development.