Abstract
Down syndrome regression disorder (DSRD) is a condition in which individuals with Down syndrome experience a decline in social and adaptive functioning in adolescence to early adulthood. Initially described as catatonic psychosis and later designated Down syndrome disintegrative disorder (DSDD), the etiology for DSRD remains unclear but has been hypothesized to relate to autoimmune function, stress, and psychiatric disease. DSRD presents heterogeneously and has no clearly established diagnostic criteria, which can complicate treatment recommendations. ECT has been used to successfully treat DSRD, but the number of reported cases remains low, especially when it is unclear whether there are comorbid catatonic features. Here, we present a case of successful use of ECT in an individual with DSRD in which catatonic features were difficult to ascertain, and we make recommendations for the use of ECT in the treatment of DSRD.
Rachubinski AL, Patel LR, Sannar EM, Kammeyer RM, Sanders J, Enriquez-Estrada BA, Worek KR, Fidler DJ, Santoro JD, Espinosa JM. JAK inhibition in Down Syndrome Regression Disorder. J Neuroimmunol. 2024 Oct 15;395:578442. doi: 10.1016/j.jneuroim.2024.578442. Epub 2024 Aug 22. PMID: 39216159; PMCID: PMC11533451.
Abstract
Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy. This case series describes three individuals with probable DSRD who received the JAK inhibitor tofacitinib and saw improvement in DSRD symptoms across multiple domains of neurological function.
Santoro JD, Jafarpour S, Khoshnood MM, Boyd NK, Vogel BN, Nguyen L, Saucier LE, Partridge R, Tiongson E, Ramos-Platt L, Nagesh D, Ho E, Rosser T, Ahsan N, Mitchell WG, Rafii MS. Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder. Am J Med Genet A. 2024 May;194(5):e63524. doi: 10.1002/ajmg.a.63524. Epub 2024 Jan 2. PMID: 38169137.
Abstract
Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions.
Santoro JD, Khoshnood MM, Nguyen L, Vogel BN, Boyd NK, Paulsen KC, Rafii MS. Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder. J Autism Dev Disord. 2023 Aug 16. doi: 10.1007/s10803-023-06057-9. Epub ahead of print. PMID: 37584771.
Abstract
Purpose: Down Syndrome Regression Disorder (DSRD) is a diagnosis of exclusion. Psychiatric and neuroimmunologic etiologies have been proposed although the exact etiology remains unknown. This study sought to review non-DSRD diagnoses at a large quaternary medical center specializing in the diagnosis of DSRD and compare clinical characteristics between those diagnosed with DSRD and those with non-DSRD diagnoses.
Methods: The authors performed a single-center retrospective, chart-based, review of referrals for developmental regression in individuals with Down syndrome.
Results: Two hundred and sixty-six individuals were evaluated for DSRD and of these, 54 (20%) ultimately had alternative diagnoses. Individuals with DSRD were more likely to have shorter nadir to clinical symptoms (p = 0.01, 95% CI: 0.36-0.47) and have preceding triggers (p < 0.001, 95% CI: 1.13-1.43) compared to those with alternative diagnoses. Individuals with non-DSRD diagnoses were more likely to be born premature (p = 0.01, 95% CI: 0.51-0.87) and have a history of epilepsy (p = 0.01, 95% CI: 0.23-0.77) but were also less likely to have a history of cytokine abnormalities on bloodwork (p < 0.001, 95% CI: 1.19-1.43) and have catatonia (p < 0.001, 95% CI: 1.54-2.17). The majority of alternative diagnoses (41/54, 76%) were autism spectrum disorder. In these cases, symptoms were more likely to be longstanding (symptoms > 12 months) and earlier onset (median 8 years, IQR: 6-11). Other diagnoses included epilepsy (5/54, 9%), Celiac disease (5/54, 9%), cerebrovascular disease (3/54, 6%).
Conclusions: This study identifies that 20% of individuals referred with concerns for DSRD have alternative diagnoses. The majority of these diagnoses were autism, but rare treatable conditions were also identified, highlighting the importance of a thorough neurodiagnostic assessment.
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