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Movement Disorders in Patients With Genetic Developmental and Epileptic Encephalopathies
Sterre van der Veen1, Gabrielle T W Tse1, Alessandro Ferretti1
1From the University Medical Center Groningen (S.v.d.V.), the Netherlands; Austin Health (G.T.W.T.), Melbourne, Australia; Bambino Gesù Children's Hospital (A.F., M.T.); Bambino Gesù Children's Hospital (G.G.), Tor Vergata University, Rome, Italy; Radboud UMC (B.P.), Nijmegen, the Netherlands; Ospedale Pediatrico Bambino Gesù (N.S.), Rome, Italy; Westmead Hospital (V.S.C.F.); and University of Melbourne, Austin Health and Royal Children's Hospital (I.E.S.), Australia.
Background And Objectives:
Movement disorders (MDs) are underrecognized in the developmental and epileptic encephalopathies (DEEs). There are now more than 800 genes implicated in causing the DEEs; relatively few of these rare genetic diseases are known to be associated with MDs. We identified patients with genetic DEEs who had MDs, classified the nature of their MDs, and asked whether specific patterns correlated with the underlying mechanism.
Methods:
We classified the type of MDs associated with specific genetic DEEs in a large international cohort of patients and analyzed whether specific patterns of MDs reflected the underlying biological dysfunction.
Results:
Our cohort comprised 77 patients with a genetic DEE with a median age of 9 (range 1-38) years. Stereotypies (37/77, 48%) and dystonia (34/77, 44%) were the most frequent MDs, followed by chorea (18/77, 23%), myoclonus (14/77, 18%), ataxia (9/77, 12%), tremor (7/77, 9%), and hypokinesia (6/77, 8%). In 47% of patients, a combination of MDs was seen. The MDs were first observed at a median age of 18 months (range day 2-35 years). Dystonia was more likely to be observed in nonambulatory patients, while ataxia was less likely. In 46% of patients, therapy was initiated with medication (34/77, 44%), deep brain stimulation (1/77, 1%), or intrathecal baclofen (1/77, 1%). We found that patients with channelopathies or synaptic vesicle trafficking defects were more likely to experience dystonia; whereas, stereotypies were most frequent in individuals with transcriptional defects.
Discussion:
MDs are often underrecognized in patients with genetic DEEs, but recognition is critical for the management of these complex neurologic diseases. Distinguishing MDs from epileptic seizures is important in tailoring patient treatment. Understanding which MDs occur with different biological mechanisms will inform early diagnosis and management.
Insights
Movement disorders are often missed in developmental and epileptic encephalopathies (DEEs). Identifying specific movement disorder patterns linked to genetic causes aids early diagnosis and management of these rare diseases.
Area of Science:
- Neurology
- Genetics
- Developmental Biology
Background:
- Movement disorders (MDs) are frequently underrecognized in patients with developmental and epileptic encephalopathies (DEEs).
- Over 800 genes are linked to DEEs, but few are associated with MDs.
- Understanding the relationship between genetic DEEs and MDs is crucial for patient care.
Purpose of the Study:
- To identify and classify movement disorders in patients with genetic DEEs.
- To analyze correlations between specific MD patterns and underlying genetic mechanisms.
- To improve diagnosis and management strategies for DEEs with MDs.
Main Methods:
- A large international cohort of 77 patients with genetic DEEs was analyzed.
- Movement disorders were classified based on type and onset.
- Genetic mechanisms were correlated with observed MD patterns.
Main Results:
- Stereotypies (48%) and dystonia (44%) were the most common MDs observed.
- Dystonia was more frequent in nonambulatory patients; ataxia was less frequent.
- Specific MDs correlated with genetic defects: dystonia with channelopathies/synaptic defects, stereotypies with transcriptional defects.
Conclusions:
- Movement disorders are common and diverse in genetic DEEs.
- Recognizing MD patterns associated with specific genetic defects can inform diagnosis and management.
- Distinguishing MDs from seizures is vital for effective treatment of these complex neurological conditions.
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