Developmental Regression in Down Syndrome Should Prompt Careful Evaluation

By Will Boggs MD

June 02, 2020

NEW YORK (Reuters Health) - Down syndrome disintegrative disorder (DSDD), a loss of previously acquired functioning in young people with Down syndrome, is not part of the natural history of the syndrome and its appearance calls for careful evaluation and management, according to a new review.

"Behavioral and neurocognitive regression in persons with DS is nearly always abnormal and should be identified early, especially in the absence of other external or environmental stressors/triggers," said Dr. Jonathan D. Santoro of Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California.

"It is possible that the window for intervention in persons with DSDD is small, and early identification, referral, and potentially treatment are the goal," he told Reuters Health by email.

The etiology, pathophysiology and therapeutic options for DSDD remain unclear, Dr. Santoro and colleagues note in Pediatrics. Among the proposed causes are immune dysregulation and psychological stress triggering neuropsychiatric manifestations.

The initial phase of DSDD can include symptoms of mood lability, decreased participation in activities of daily living, new-onset insomnia, social withdrawal, autistic-like regression, mutism and catatonia.

Following the acute regression phase, which may last for around six months, is a chronic phase in which previous skills may not be completely recovered.

Clinicians faced with DS patients with regression should pursue a comprehensive psychosocial and medical evaluation of potential secondary causes of behavioral change and regression, the authors advise. They suggest a five-tier diagnostic workup that moves from more common to less common differential diagnoses.

"The best assessment (in a perfect world) is done by a multidisciplinary team that includes a pediatrician/primary-care physician (preferably the medical home), neurologist, and psychiatrist," Dr. Santoro said. "As most centers are not set up for this, evaluation by a neurologist would be necessary to rule in/out a neuroinflammatory component, as the core neurodiagnostic studies are lumbar puncture, EEG, and MRI, all of which are under a neurologist's scope."

Several therapies have brought some clinical benefits in patients with DSDD, including antipsychotics, selective serotonin-reuptake inhibitors (SSRIs), and anticholinergic drugs for the neuropsychiatric disturbances; high-dose benzodiazepines and electroconvulsive therapy for DSDD with catatonia; and various immunotherapeutic regimens to address the putative autoimmune etiology of DSDD.

"DSDD has been reported for many years in the literature but never really explored, with both psychiatrists and neurologists working it up and treating it in different ways," Dr. Santoro said. "Given the known neuroimmunologic phenomenon observed in persons with DS, it is very possible that there is an autoimmunity component to the disorder, and this is the next step for what we need to research. As we learn more and more about the potential immune involvement in psychiatric disorders, the potential for immune involvement in DSDD is even greater."

"There are neurologists (like myself and the team publishing the manuscript) who are actively investigating cases of regression in persons with DS and may be able to provide neurodiagnostic workup and potentially treatment," he concluded. "I've had many patients take several years to find their way into a neurology clinic, even in the setting of severe symptoms, which is unfortunate and something our team is looking to improve upon."

SOURCE: Pediatrics, online May 29, 2020.