Expanding the Phenotype of BCL11B-related Disorders: A Case Series of Primary Movement Disorders with Literature Review
Ginny Lane1, Audrey Hunt1, Lia Thibodaux1, Lubna Jafri1, Leah Chapman2, Jessica Tate2, Alexander Paciorkowski3, Jaclyn Martindale4
1Wake Forest Baptist Health, 2Atrium Health Wake Forest Baptist, 3Department of Neurology, University of Rochester School of Medicine, 4Wake Forest Medical Center
Objective:
Not applicable.
Background:
BCL11B-related disorder is an uncommon neurodevelopmental disorder with movement disorders rarely described as a prominent clinical feature.
Design/Methods:
We report a family of four patients: a father, twin sons, and their younger brother. Case 1 (Twin B) presented with expressive speech and fine motor delays as a toddler with progression to generalized dystonia (L>R), co-occurring level 1 autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), anxiety, and dysmorphic features. Dystonia failed symptomatic treatment despite optimizing medications; he is undergoing deep brain stimulation evaluation. Case 2 (Twin A) had early onset fine motor and articulation difficulties. He developed right hemibody dystonia with frequent hyperkinetic-choreiform movements, and has co-occurring level 1 ASD, OCD, anxiety, and dysmorphic features. Case 3 (younger brother) presented with a “galloping” run as a toddler, then focal left leg dystonia, which rapidly progressed to generalized dystonia and retrocolis. His symptoms became disabling despite medication optimization, prompting deep brain stimulation evaluation. He also presented with poor articulation and effortful speech. Case 4 (Father) has long-standing clumsiness and toe-walking, developed L>R hand tremor at age 20 followed by spasmodic torticollis, akathisia, dystonia, and severe chorea over time. Extensive workup revealed all four had a novel inherited heterozygous variant of unknown significance in the gene BCL11B (c.2422 T>C). Cases 1, 2, and 3 underwent neuropsychological testing. None of the cases met criteria for intellectual disability, and they all demonstrated relative strengths in language skills.
Results:
Previous case studies of BCL11B-related disorder (1-8) documented five cases with movement-related features. Including our cases, 9 of 32 (28%) have movement-related features, and 6 of 9 (67%) have dystonia as a prominent feature.
Conclusions:
With our case report, there appears to be a stronger association between BCL11B-related disorder and movement disorders than previously thought.