Postnatal Care Practice and the Facilitating Factors Among Japanese Primary Care Physicians: A Cross-Sectional Study.

Fragile X syndrome (FXS) is caused by a full expansion of CGG repeats (≥200 repeats) in the 5′ region of the fragile X messenger ribonucleoprotein () gene. It has an estimated prevalence of 1 in 5000 males and 1 in 8000 females (). This expansion typically results in methylation of the gene, leading to gene silencing and little or no production of the protein (FMRP), resulting in the clinical features of FXS, including intellectual disability (; ). The gene premutation (PM) with 55–200 CGG repeats commonly occurs in approximately 1 in 400 males and 1 in 200 females (; ). Aging individuals with the PM may develop Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), which may present with intention tremor, cerebellar ataxia, cognitive decline, and brain changes detected via magnetic resonance imaging (MRI) (; ). These changes include white matter hyperintensities (WMHs) in the middle cerebellar peduncles (MCP sign), splenium, and/or periventricular areas (; ). Current studies on FXTAS have focused on the impact of the premutation on cognitive abilities, particularly executive functioning (EF), and memory issues as an early manifestation of FXTAS (; ; ). FXTAS patients experience mRNA toxicity, leading to issues such as protein sequestration, DNA damage, and repeat-associated non-AUG (RAN) translation which results in cell death, particularly of astrocytes and neurons (; ). The diagnostic criteria for FXTAS are based on a combination of clinical features (tremor and ataxia) in addition to characteristic radiological features, including WMHs in the MCP and in the splenium of the corpus callosum (). Both the clinical presentation and these associated radiological findings are more commonly observed and tend to be more severe in male carriers (). By their 70s, about 48% of male PM carriers develop FXTAS. In those aged 80 years and above, this number increases to 75% (; ; ). However, clinical presentation can vary significantly in terms of severity, age of onset, and overall course (; ; ; ). Since the gene responsible for FXTAS is X-linked, it affects males and females differently. Female carriers tend to have lower penetrance and milder clinical symptoms compared to males because of the protective effects of their second X chromosome (; ). Symptom severity in female PM carriers may be related to X-inactivation patterns that favor higher expression of the normal allele for the protective effect (). Recent studies have explored biomarkers that aid in identifying carriers at higher risk of developing FXTAS (; ; , ). Despite these efforts, clinical measures to assess individual risk or early disease detection are still limited. Clinical heterogeneity persists after disease onset, where some patients experience a sudden increase in symptom severity, especially with concomitant excessive alcohol intake or opioid use (), while in others, the disease progresses more gradually (; ).