Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder.
When a child with Down syndrome regresses, autism is the most common hidden cause—screen for it first.
01Research in Context
What this study did
Doctors looked at 266 Down syndrome patients who were sent to them because the kids had lost skills. They ran full medical and behavioral work-ups to see if something else was going on.
Out of these referrals, the children got a brand-new main diagnosis. The team counted how often each new label appeared.
What they found
Autism was the commonest surprise finding. Forty-one of the 54 new diagnoses (a large share) were autism spectrum disorder. Other new diagnoses included epilepsy and ADHD.
In short, one in every five 'Down syndrome regression' cases actually had a different reason for the skill loss.
How this fits with other research
Mount et al. (2011) found that a large share of kids with autism lose skills before age three. D et al. now show that when a child with Down syndrome regresses, autism is the most likely hidden cause. The two studies line up: regression often equals autism, no matter the starting diagnosis.
Busch et al. (2010) showed that children with autism have more behavior problems than matched children with Down syndrome alone. The new data explain part of that gap: some 'Down syndrome' kids in past comparisons probably had undiagnosed autism driving the tougher behaviors.
Giserman-Kiss et al. (2020) proved that an early autism label is stable a large share of the time. This supports the new paper's push to rule-in autism first; once the label is made, it sticks and opens the door to evidence-based autism treatment.
Why it matters
If a child with Down syndrome starts to lose words, play skills, or daily living skills, pause before blaming 'Down syndrome regression disorder.' Screen for autism right away with the ADOS and a full developmental history. Catching autism early gives the child access to ABA, speech, and social-skills services that work. It also saves families from months of medical hunting and gives you, the BCBA, a clear treatment target.
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02At a glance
03Original 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.
Journal of autism and developmental disorders, 2025 · doi:10.1177/0883073814554654