Catatonia is a highly morbid psychomotor and affective disorder, which can affect autistic individuals with and without intellectual disability. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments in autistic individuals has not been described. We conducted a prospective observational cohort study of patients with autism and co‐morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024. Data investigating pharmacologic interventions, and clinical measures including the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), Kanner Catatonia Examination (KCE), and Clinical Global Impression—Improvement (CGI‐I) were collected. Forty‐five autistic patients with co‐morbid catatonia were treated during the study period. The mean age was 15.6 (SD = 7.9) years [Mdn = 16.0, range 6.0–31.0]. Forty‐one patients (91.1%) met criteria for autism with co‐occurring intellectual disability. All patients received pharmacotherapy. Forty‐four (97.8%) were treated with benzodiazepines with a mean maximal daily dose of 17.4 mg (SD = 15.8) lorazepam equivalents. Thirty‐five patients (77.8%) required more than one medication class for treatment. Sixteen (35.6%) patients received electroconvulsive therapy. Fourteen patients (31.1%) attempted to taper off benzodiazepines after achieving clinical improvement during the study period; of these, 5 patients (11.1%) were successfully tapered off, and the remaining 9 (17.8%) discontinued the taper due to a return of catatonic symptoms. Statistically significant improvement was observed across all clinical domains except the KCS. However, the majority remained at least partially symptomatic over the study period. Three patients (6.7%) died over the study period. Despite clinical improvements while receiving the gold standard for psychopharmacologic management of catatonia, chronic symptoms remained for the majority of catatonia patients over the study period, and few were able to taper and discontinue benzodiazepine treatment. Notably, the open label design of this study is a limiting factor when interpreting the results.

The 15q11.2 BP1-BP2 deletion (Burnside-Butler) syndrome is emerging as the most common cytogenetic finding in patients with neurodevelopmental or autism spectrum disorders (ASD) presenting for microarray genetic testing. Clinical findings in Burnside-Butler syndrome include developmental and motor delays, congenital abnormalities, learning and behavioral problems, and abnormal brain findings. To better define symptom presentation, we performed comprehensive cognitive and behavioral testing, collected medical and family histories, and conducted clinical genetic evaluations. The 15q11.2 BP1-BP2 region includes the TUBGCP5, CYFIP1, NIPA1, and NIPA2 genes. To determine if additional genomic variation outside of the 15q11.2 region influences expression of symptoms in Burnside-Butler syndrome, whole-exome sequencing was performed on the parents and affected children for the first time in five families with at least one parent and child with the 15q1l.2 BP1-BP2 deletion. In total, there were 453 genes with possibly damaging variants identified across all of the affected children. Of these, 99 genes had exclusively de novo variants and 107 had variants inherited exclusively from the parent without the deletion. There were three genes (APBB1, GOLGA2, and MEOX1) with de novo variants that encode proteins evidenced to interact with CYFIP1. In addition, one other gene of interest (FAT3) had variants inherited from the parent without the deletion and encoded a protein interacting with CYFIP1. The affected individuals commonly displayed a neurodevelopmental phenotype including ASD, speech delay, abnormal reflexes, and coordination issues along with craniofacial findings and orthopedic-related connective tissue problems. Of the 453 genes with variants, 35 were associated with ASD. On average, each affected child had variants in 6 distinct ASD-associated genes ($\overline{x}$ = 6.33, sd = 3.01). In addition, 32 genes with variants were included on clinical testing panels from Clinical Laboratory Improvement Amendments (CLIA) approved and accredited commercial laboratories reflecting other observed phenotypes. Notably, the dataset analyzed in this study was small and reported results will require validation in larger samples as well as functional follow-up. Regardless, we anticipate that results from our study will inform future research into the genetic factors influencing diverse symptoms in patients with Burnside-Butler syndrome, an emerging disorder with a neurodevelopmental behavioral phenotype.

Introduction: Hyperactive catatonia is often unrecognized in pediatric patients due to its clinical heterogeneity, though it is often seen in children with neurodevelopmental disabilities, especially autism spectrum disorder (ASD). Emerging evidence implicates hyperactive catatonia in more cases of self-injury and aggression in ASD than previously thought. Objectives: The study seeks to describe cases of hyperactive catatonia in SYNGAP-1 mutation and examine existing literature for symptomatic overlap between previously-described clinical and behavioral phenotypes of individuals with SYNGAP-1 mutations and catatonia. Methods: The study describes two cases of an adolescent and a young adult with SYNGAP-1 mutation and ASD presenting with hyperactive catatonia, which are the first reports of catatonia in individuals known to have a pathogenic variant in SYNGAP-1. A systematic review was undertaken during which 101 articles were screened. 13 articles were then examined for neurological and behavioral features present in participants with SYNGAP-1 mutations which are seen in catatonia. Results: The systematic review demonstrates that clinical features suggestive of catatonia are frequently seen among individuals with SYNGAP-1 mutations, including verbal impairment, psychomotor symptoms, aggression, oral aversion, and incontinence. These features were also present in the cases of catatonia in SYNGAP-1 mutations presented here. Both patients showed clinical improvement with use of a long-acting benzodiazepine, and one patient showed benefit from electroconvulsive therapy. Conclusions: This symptomatic overlap revealed in the systematic review, including symptoms seen in the reported cases, raises the possibility that diagnoses of catatonia may have been missed in the past in individuals with SYNGAP-1 mutations. Self-injurious behavior and aggression, which are hallmarks of hyperactive catatonia, are commonly part of the behavioral phenotype of SYNGAP-1-related disorders. Clinicians should consider catatonia as a cause of such symptoms in individuals with SYNGAP-1 mutations, as effective treatment can result in significant improvement in safety and quality of life.

Objective: Catatonia is a neuropsychiatric disorder that occurs in pediatric patients with a range of associated medical, psychiatric, and neurodevelopmental disorders (NDDs). This study describes hospital care of pediatric catatonia patients and compares treatments for neurotypical patients and those with NDDs. Methods: Retrospective cohort study from 1/1/2018 to 6/1/2023 of two academic medical centers of patients aged 18 and younger with catatonia. Patients were retrospectively assessed using the clinical global impressions-improvement (CGI-I) by two independent reviewers. Results: One hundred sixty-five patients were hospitalized for catatonia, of whom 50.3% had an NDD. Median age was 15. One hundred sixty-four patients were treated with a benzodiazepine, with a median maximum 24-hour dose of 6 mg lorazepam-equivalents, which did not differ for patients with and without NDDs. Electroconvulsive therapy (ECT) was utilized in 14.5% of patients. Median length of medical hospitalization was 5 days and hospitalizations were longer in neurotypical patients than in patients with NDDs. In an ordinal regression model, the probability of observing at least “much improvement” (CGI < 3) was 88.3% (95% CI: 82.4% to 92.3%), with NDD diagnosis associated with a lower odds of clinical response. Conclusions: The probability of patients achieving a CGI-I score indicating at least “much improvement” was 88.3%. Administered benzodiazepine dose and ECT treatment were similar for all patients, but neurotypical patients had longer hospitalizations than those with NDDs and had a higher odds of a more favorable clinical response. Research under controlled conditions is needed to optimize and endure equitable catatonia treatment in youth.

Introduction: Catatonia is a highly morbid psychomotor and affective disorder which can affect autistic individuals with and without profound impairment. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments has not been described. Methods: We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1 ^st , 2021 to May 31 ^st , 2024. Data investigating pharmacologic interventions, and clinical measures including the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), Kanner Catatonia Examination (KCE), and Clinical Global Impression – Improvement (CGI-I) were collected. Results: Forty-five patients were identified with 39 (86.7%) meeting criteria for profound autism. All patients received pharmacotherapy. 44 (97.8%) were treated with benzodiazepines with a mean maximal daily dose of 17.4 mg (SD=15.8) lorazepam equivalents. Thirty-five patients (77.8%) required more than one medication class for treatment. Fourteen patients (31.1%) attempted to taper off benzodiazepines during the study period; of these, 5 patients (11.1%) were successfully tapered off, and the remaining 9 (17.8%) discontinued the taper due to a return of catatonic symptoms. Statistically significant improvement was observed across all clinical domains except the KCS. However, the majority remained symptomatic over the study period. Conclusions: Despite clinical improvements while receiving the gold standard for psychopharmacologic management of catatonia, chronic symptoms remained for the majority of catatonia patients over the study period, and few were able to taper and discontinue benzodiazepine treatment. Lay Summary: Catatonia is a condition which can significantly impact the quality of life for autistic individuals with and without profound impairment. Symptoms of catatonia such as aggression and self-injury can improve with treatment. However, over the three-year period of this study, most patients experienced residual symptoms, and few could discontinue psychotropic medication.