Objective: To describe the functional impact and phenotypic variability of tremor in two adult sisters with Angelman syndrome (AS) and explore a possible contribution of valproate (VPA) to tremor and gait worsening

Background: AS is a neurogenetic disorder characterized by developmental delay,epilepsy,ataxia, and abnormal movements.Tremor, myoclonus,and dystonia are increasingly recognized in adolescents and adults with AS [1].Tremor occurs in up to 66% of individuals and ~55% of adults,suggesting increased prevalence with age [2].Antiseizure medications such as VPA may exacerbate tremor and motor dysfunction,including gait and balance impairment [3]

Method: Two adult sisters with AS were evaluated for tremor in a movement disorders clinic;history and neurological exam assessed tremor phenomenology,distribution,gait abnormalities,and functional impact

Results: 51-year-old woman with AS and frontotemporal epilepsy had been treated with VPA 600 mg/day for 3 years.Over the preceding year,she developed progressive bilateral hand tremor with postural and kinetic components(left greater than right),interfering with ADLs (eating,drawing),along with progressive gait instability and impaired balance.

Neurological examination showed left-predominant kinetic and postural tremor,evident on postural testing and Archimedes spiral drawing,and an ataxic gait with impaired balance and inability to perform tandem gait.

Levetiracetam had been avoided due to baseline anxiety/irritability,and antiseizure therapy had remained VPA.Given the progressive tremor and functional impairment,transition from VPA to lamotrigine was initiated to assess a possible medication-related contribution.

Her 48-year-old sister,also with AS and temporal epilepsy treated with levetiracetam 1 g BID,exhibited mild intention tremor without functional impairment.

No dystonia,myoclonus, or other abnormal movements were observed in either patient

Conclusion: Tremor in AS, often considered of limited impact,may be clinically disabling and associated with gait worsening, with marked phenotypic variability between affected siblings.VPA may exacerbate tremor and motor dysfunction,and medication effects should be considered when evaluating worsening neurological symptoms.These observations suggest greater functional significance of tremor and gait impairment in AS than previously recognized

References: 1. Carson, R. P., Riordan, H., Short, B., Davis, T., Fang, J., Giritharan, A., … & Aravamuthan, B. (2025). Myoclonic Dystonia: A Common Phenomenology in the Pleomorphic Movements of Angelman Syndrome. Movement Disorders Clinical Practice, 12(9), 1313-1325.
2. Prasad, A., Grocott, O., Parkin, K., Larson, A., & Thibert, R. L. (2018). Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases. American Journal of Medical Genetics Part A, 176(6), 1327-1334.
3. Shaaya, E. A., Grocott, O. R., Laing, O., & Thibert, R. L. (2016). Seizure treatment in Angelman syndrome: A case series from the Angelman Syndrome Clinic at Massachusetts General Hospital. Epilepsy & Behavior, 60, 138-141.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tremor-and-gait-worsening-in-angelman-syndromephenotypic-variability-in-two-adult-sisters-with-possible-valproate-related-exacerbation/