Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1.

We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population.

Using the Brief-BESTest paired with a novel algorithm to provide targeted balance interventions for people with subacute stroke: a feasibility study.

BACKGROUND: Balance is a common mobility limitation following stroke, but determination of the most effective balance-related plan of care can be difficult due to multiple balance impairments that vary between individuals. The Brief-BESTest is a validated outcome measure for balance based on six systems of postural control. It may also be a useful tool to guide clinicians in their balance plan of care design. OBJECTIVE: The objective of this study was to determine the feasibility of a quantitative balance plan of care for patients with subacute stroke, using a novel algorithm that utilizes the scoring design of the Brief-BESTest. The authors hypothesized that this plan of care could create targeted balance interventions among this population. METHODS: Eligible patients with subacute stroke at an inpatient rehab facility completed the Brief-BESTest within 1 week of admission. The subjects participated in specific interventions based on test section scores during their rehab stay. RESULTS: Five subjects completed testing and participated in targeted balance interventions, addressing three to five systems of postural control. Subjects demonstrated improved Brief-BESTest overall scores by 2, 1, 7, 4, and 6 points from admission to discharge. Improvements in section scores were primarily seen in the systems of postural control identified by the algorithm. All subjects improved in Functional Independence Measure (FIM™)30 scores for locomotion (walking and stairs) by 5, 6, 7, 6, and 9 points, respectively. All subjects were discharged to the community. CONCLUSION: Our observational study found this method of assessment and intervention to be feasible in the subacute stroke population and was associated with improved balance scores and improved functional mobility. Further study is warranted to determine effectiveness and efficiency.