Patients with Sturge-Weber disease who have the onset of seizures in infancy invariably face a progressively downhill course which leaves them severely hemiplegic, demented and usually institutionalized because of uncontrolled seizures. During the past 12 years, we have carried out 6 hemispherectomies in infants under 1 year of age who presented with seizures and Sturge-Weber disease. The results have been gratifying. Seizures have stopped, hemipareses have been minimal and intellectual development has been good.

BackgroundRett syndrome (RTT) is a severe neurodevelopmental disorder with complex medical comorbidities extending beyond the nervous system requiring the attention of health professionals. There is no peer-reviewed, consensus-based therapeutic guidance to care in RTT. The objective was to provide consensus on guidance of best practice for addressing these concerns.MethodsInformed by the literature and using a modified Delphi approach, a consensus process was used to develop guidance for care in RTT by health professionals.ResultsTypical RTT presents early in childhood in a clinically recognisable fashion. Multisystem comorbidities evolve throughout the lifespan requiring coordination of care between primary care and often multiple subspecialty providers. To assist health professionals and families in seeking best practice, a checklist and detailed references for guidance were developed by consensus.ConclusionsThe overall multisystem issues of RTT require primary care providers and other health professionals to manage complex medical comorbidities within the context of the whole individual and family. Given the median life expectancy well into the sixth decade, guidance is provided to health professionals to achieve current best possible outcomes for these special-needs individuals.

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.

BackgroundRett syndrome (RTT) is a severe, progressive neurodevelopmental disorder with multisystem comorbidities that evolve across a patient’s lifespan requiring attentive coordination of subspecialty care by primary care providers. A comprehensive, up-to-date synthesis of medical comorbidities in RTT would aid care coordination and anticipatory guidance efforts by healthcare providers. Our objective was to review and summarise published evidence regarding prevalence of RTT medical comorbidities across all relevant organ systems.MethodsSearch of PubMed from January 2000 to July 2019 was performed using the search terms (Rett and MECP2 AND patient) OR (Rett and MECP2 AND cohort). Articles reporting the prevalence of clinical findings in RTT were assessed with respect to the size and nature of the cohorts interrogated and their relevance to clinical care.ResultsAfter review of over 800 records, the multisystem comorbidities of RTT were summarised quantitatively from 18 records comprising both retrospective and prospective cohorts (31–983 subjects). Neurological comorbidities had the highest prevalence, occurring in nearly all individuals with gastrointestinal and orthopaedic concerns almost as prevalent as neurological. With the exception of low bone mineral content which was relatively common, endocrine comorbidities were seen in only around one-third of patients. Although more prevalent compared with the general population, cardiac conduction abnormalities were the least common comorbidity in RTT.ConclusionsEffective care coordination for RTT requires knowledge of and attention to multiple comorbidities across multiple unrelated organ systems. Many issues common to RTT can potentially be managed by a primary care provider but the need for sub-specialist referral can be anticipated. Since the median life expectancy extends into the sixth decade with evolving subspecialty requirements throughout this time, paediatric providers may be tasked with continued coordination of these comorbidities or transitioning to adult medicine and specialists with experience managing individuals with complex medical needs.