Research Studies

Individuals with DS between the ages of 8 and 30 years, inclusive. DS is broadly defined to include complete T21, Robertsonian translocation T21, partial T21 (segmental duplication), and mosaic T21 with a diagnosis of possible or probable DSRD per 2022 consensus guidelines

Inclusion criteria 1. Individuals with DS between the ages of 8 and 30 years, inclusive. DS is broadly defined to include complete T21, Robertsonian translocation T21, partial T21 (segmental duplication), and mosaic T21. 2. Diagnosis of possible or probable DSRD per 2022 consensus guidelines. 3. Must agree to complete a washout of any medications intended to treat symptoms of DSRD or that may interfere with study interventions. 4. Must agree to random treatment assignment. 5. Must be fully vaccinated for COVID-19, as defined by current CDC guidance and definitions. 6. Must be able to present with a study partner or legal guardian at all study visits. Exclusion Criteria General 1. Weight less than 40 kg. 2. Pregnant or breast feeding. 3. Past or current tobacco smoking. 4. Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements. 5. Known allergies, hypersensitivity, or intolerance to lorazepam, IVIG, or tofacitinib. 6. Participants may be excluded for other unforeseen reasons or confounding reasons for DSRD symptoms at the study doctor’s (SD’s) discretion. Co-occurring Conditions 7. Any co-occurring genetic disorder. 8. Active symptomatic cardiac disease. 9. Clinically significant chronic or active viral infection, including but not limited to HIV, hepatitis, CMV, EBV, HSV or untreated tuberculosis. 10. Untreated chronic or active bacterial infection. 11. Untreated hypothyroidism or hyperthyroidism. 12. History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster. 13. History of malignancy (solid tumor or leukemia). 14. Moyamoya syndrome or stroke (active or prior). 15. Baseline abnormal renal function indicative of moderate or severe renal disease by eGFR <=45. 16. History of acute narrow-angle glaucoma. 17. History of venous or arterial thrombosis. 18. IgA deficiency with antibodies against IgA. 19. Pathogenic neuronal autoantibody positivity against established causes of autoimmune encephalopathy in CSF. 20. Anyone with a history of anaphylaxis or a severe systemic response to blood or plasma-derived products. Additional criteria exist.