Objective Rett syndrome, CDKL5‐deficiency disorder, FOXG1 disorder, and MECP2 duplication disorder are developmental encephalopathies with shared and distinct features. Although they are historically linked, no direct comparison has been performed. The first head‐to‐head comparison of clinical features in these conditions is presented. Methods Comprehensive clinical information was collected from 793 individuals enrolled in the Rett and Rett‐Related Disorders Natural History Study. Clinical features including clinical severity, regression, and seizures were cross‐sectionally compared between diagnoses to test the hypothesis that these are 4 distinct disorders. Results Distinct patterns of clinical severity, seizure onset age, and regression were present. Individuals with CDKL5‐deficency disorder were the most severely affected and had the youngest age at seizure onset (2 months), whereas children with MECP2 duplication syndrome had the oldest median age at seizure onset (64 months) and lowest severity scores. Rett syndrome and FOGX1 were intermediate in both features. Smaller head circumference correlates with increased severity in all disorders and earlier age at seizure onset in MECP2 duplication syndrome. Developmental regression occurred in all Rett syndrome participants (median = 18 months) but only 23 to 34% of the other disorders. Seizure incidence prior to the baseline visit was highest for CDKL5 deficiency disorder (96.2%) and lowest for Rett syndrome (47.5%). Other clinical features including seizure types and frequency differed among groups. Interpretation Although these developmental encephalopathies share many clinical features, clear differences in severity, regression, and seizures warrant considering them as unique disorders. These results will aid in the development of disease‐specific severity scales, precise therapeutics, and future clinical trials. ANN NEUROL 2020;88:396–406.

Objective The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease‐modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. Method Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome‐specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. Results At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT‐related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow‐up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. Interpretation The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790–802

INTRODUCTION:The fourth trimester is a time of great physical and emotional challenge. To help patients navigate this period, we created the Healing at Home (H@H) program, which combined expedited discharge with a 24/7 bidirectional postpartum support chatbot.METHODS:Clinical outcomes, abstracted from medical record and patient report via text message, were evaluated for patients enrolled in H@H (March 2020 to September 2021) compared to patients delivering prior to program implementation (July to December 2019). Enrolled patients had a full-term singleton vaginal delivery of a non-small-for-gestational-age infant without postpartum hemorrhage (>1,000 cc), a low-risk sepsis risk score, a low- to intermediate-risk bilirubin, and lack of significant maternal comorbidities (eg, preeclampsia, preexisting diabetes). Institutional review board waiver for this quality improvement study was obtained.RESULTS:There were 490 patients enrolled in H@H versus 309 in preintervention group. The groups were similar in parity, race, ethnicity, and insurance status. There was no difference in the primary outcome, postpartum visit attendance (76.9% versus 76.1%, P=.77). H@H patients had a shorter postpartum length of stay (33.3 versus 46.7 hours, P<.001), higher rates of exclusive breastfeeding at 1 week (59.2% versus 57.0%, P=.02), and a higher rate of contraceptive use (55% versus 44%, P=.01), with no difference in maternal unscheduled visits or hospital readmissions.CONCLUSION:This innovative postpartum program was associated with a shorter length of stay and improvement in contraceptive acceptance and breastfeeding without increasing unscheduled visits. Future studies should evaluate the cost-effectiveness of this program and expansion to higher-risk patients including those with cesarean delivery and medical comorbidities.