Muenke syndrome: An international multicenter natural history study.

Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal, and calcaneal fusions, and behavioral differences. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings. Muenke syndrome constitutes the most common syndromic form of craniosynostosis, with an incidence of 1 in 30,000 births and is defined by the presence of the p.Pro250Arg mutation in FGFR3. Participants were recruited from international craniofacial surgery and genetic clinics. Affected individuals, parents, and their siblings, if available, were enrolled in the study if they had a p.Pro250Arg mutation in FGFR3. One hundred and six patients from 71 families participated in this study. In 51 informative probands, 33 cases (64.7%) were inherited. Eighty-five percent of the participants had craniosynostosis (16 of 103 did not have craniosynostosis), with 47.5% having bilateral and 28.2% with unilateral synostosis. Females and males were similarly affected with bicoronal craniosynostosis, 50% versus 44.4% (P = 0.84), respectively. Clefting was rare (1.1%). Hearing loss was identified in 70.8%, developmental delay in 66.3%, intellectual disability in 35.6%, attention deficit/hyperactivity disorder in 23.7%, and seizures in 20.2%. In patients with complete skeletal surveys (upper and lower extremity x-rays), 75% of individuals were found to have at least a single abnormal radiographical finding in addition to skull findings. This is the largest study of the natural history of Muenke syndrome, adding valuable clinical information to the care of these individuals including behavioral and cognitive impairment data, vision changes, and hearing loss.

Novel Approach to Characterize Heterogeneity in an Aerobic Exercise Intervention.

PURPOSE: Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-age and older adults who participated in a prescribed 6-month supervised aerobic exercise intervention as part of the Brain in Motion study. METHODS AND RESULTS: Group-based multitrajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first 3 months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "high-increasing" (HI) and "low-increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and (i) demographic characteristics; (ii) physiological characteristics, including cardiovascular and cerebrovascular function; (iii) genetic characteristics; and (iv) adherence with American College of Sports Medicine guidelines on exercise for older adults. Of the 196 participants, 54.1% met the American College of Sports Medicine aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (maximal oxygen uptake; odds ratio, 1.27; P < 0.01) was significantly different between these trajectory subgroups in males, and cerebrovascular function (cerebrovascular resistance; odds ratio, 0.14; P < 0.01) was significantly different between these trajectory subgroups in females. CONCLUSION: This novel approach to tracking a prespecified exercise program highlights that there are individual and group-specific variations within a prescribed exercise intervention. Characterizing exercise adherence in this way holds promise in developing optimized exercise prescriptions tailored to individual baseline characteristics, and additionally highlighting those participants at greatest risk of not meeting minimum dosage requirements for physiological and/or cognitive health.

Aerobic exercise increases cortisol awakening response in older adults.

Evidence from both preclinical and clinical studies suggests aerobic exercise may dampen age-related decline in cognitive performance. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function and reactivity may be a mechanism by which aerobic exercise benefits cognitive performance, and reduces perceived stress. This investigation was completed as an ancillary investigation of the Brain in Motion (BIM) study, a 6-month supervised aerobic exercise intervention. Participants were generally healthy and screened for inclusion/exclusion criteria for the parent study. Thirty-eight participants were recruited (Mean age = 65.0 [SD = 5.1]; 60% female) and the final longitudinal sample was 32 participants. Participants provided a passive drool sample at: waking, 15, 30, and 45 min post-waking to assess the cortisol awakening response (CAR) and 3, 6, 9, and 12 h post-waking to assess daily area under the curve for cortisol. Salivary cortisol was quantified by liquid chromatography coupled to tandem mass spectrometry. The exercise intervention increased CAR but no differences were observed in daily AUC. In addition, larger increases in CAR were positively associated with greater decreases in subjective stress. Thus, aerobic exercise improved the CAR in otherwise healthy, but sedentary older adults and greater improvements in CAR were associated with greater reductions in perceived stress.