Sleep apnea in fragile X premutation carriers with and without FXTAS

Abstract

This report seeks to establish the prevalence of sleep apnea in patients with the FMR1 premutation with and without FXTAS and to determine any correlation between CGG repeat and FMR1 mRNA levels with sleep apnea prevalence. Demographic and medical data from 430 (229 males, 201 females) participants were used in this analysis. Participants included premutation carriers with (n=118) and without FXTAS (n=174) as well as controls without the premutation (n=123). Logistic regression models were employed to estimate the odds ratio of sleep apnea relative to controls, adjusted for age and gender, and also to examine potential association with CGG size and FMR1 mRNA expression level. The observed proportion of sleep apnea in premutation carriers with and without FXTAS and controls are 31.4% (37/118), 8.6% (15/174), and 13.8% (17/123), respectively. The adjusted odds of sleep apnea for premutation carriers with FXTAS is about 3.4 times that compared to controls (odds ratio, OR=3.4, 95% CI 1.8 to 7.4; p=0.001), and similarly relative to premutation carriers without FXTAS (OR=2.9, 95% CI 1.2 to 6.9; p=0.014). The risk of sleep apnea was not different between controls and premutation carriers without FXTAS. The presence of sleep apnea is not associated with CGG repeat numbers nor FMR1 mRNA expression level among premutation carriers. Our data supports a higher prevalence and risk of sleep apnea in patients with FXTAS. We recommend that all patients diagnosed with FXTAS be screened for sleep apnea given the negative and perhaps accelerative impact sleep apnea may have on their FXTAS progression.

Psychiatric Disorders Associated with FXTAS

“…Men with the premutation often have type II diabetes, hypertension, sleep apnea, migraine headaches, and cardiac disease [3, 35, 36]. Chonchaiya et al [37] surveyed daughters of men with FXTAS (who are obligate carriers, since they received the X chromosome from their fathers) and found higher rates of neurological symptoms including tremor, balance, and memory problems, as well as higher rates of psychiatric problems (anxiety and insomnia) than age matched, non-carrier control women.…”

Fatigue and body mass index in the Fragile X premutation carrier

“…[37] Here we see a roughly three point difference in mean BMI between control subjects and FXTAS carriers that could correspond with the roughly three-fold increase in sleep apnea prevalence seen in the literature. [6] Further, the lack of difference in mean BMI between premutation carriers without FXTAS and control patients mirrors the non-significant difference in prevalence of sleep apnea between these populations. Beyond sleep apnea, the finding of increased BMI raises a host of health concerns about premutation carriers later in life, perhaps for diabetes and coronary artery disease in particular.…”

“…[30] Their mean score was similar to that found in other neurodegenerative diseases such as untreated Parkinson's Disease or Amyotrophic Lateral The cause of fatigue, although hypothesized to be related to decreased mitochondrial function, is not clear from these results. Sleep apnea may play a role in fatigue given the higher prevalence of this disorder in premutation carriers with FXTAS [6] and the strong association of fatigue with sleep apnea. [35,36] However, the differences amongst the three groups were still significant even after adjusting for histories of sleep apnea.…”

“…Psychiatric disorders, such as mood and anxiety disorders, have been found to be prevalent in premutation carriers. [4] Recent evidence has also shown higher rates of migraine, [5] sleep apnea, [6] and hypertension. [7] In addition, a neurodegenerative condition known as Fragile X-associated Tremor Ataxia Syndrome (FXTAS) has been identified in premutation carriers.…”

Fragile X syndrome: A review of clinical management

“…These episodes of complete airflow cessation (apnea) or partial airflow obstruction (hypopnea) result in both frequent and transient reduction of brain oxygen levels (111). It occurs more often during rapid eye movement (REM) sleep and is rarely proceed by body movements (112).…”