TY  - JOUR
AB  - BACKGROUND: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease. CASE SERIES: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes. DISCUSSION: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.
AU  - Sorrentino, U.
AU  - Romito, L.M.*
AU  - Garavaglia, B.*
AU  - Fichera, M.*
AU  - Colangelo, I.*
AU  - Prokisch, H.
AU  - Winkelmann, J.
AU  - Necpál, J.*
AU  - Jech, R.*
AU  - Zech, M.
C1  - 70484
C2  - 55630
CY  - Unit 3n, 6 Osborn Street, London, E1 6td, England
TI  - Myoclonus and dystonia as recurrent presenting features in patients with the SCA21-associated TMEM240 p.Pro170Leu variant.
JO  - Tremor Other Hyperkinet. Mov.
VL  - 14
PB  - Ubiquity Press Ltd
PY  - 2024
SN  - 2160-8288
ER  - 

TY  - JOUR
AB  - BACKGROUND: KBG syndrome is a monogenic disorder caused by heterozygous pathogenic variants in ANKRD11. A recent single-case study suggested that the clinical spectrum of KBG syndrome, classically defined by distinctive craniofacial traits and developmental delay, may include movement disorders. CASE REPORT: We report a 24-year-old patient harboring a pathogenic de novo ANKRD11 frameshift variant. The phenotype was dominated by a progressive tremor-dominant movement disorder, characterized by rest, intention and postural tremor of the hands, voice tremor, head and tongue tremor, increased muscle tone and signs of ataxia. Additionally, the patient had a history of mild developmental delay and epilepsy. DISCUSSION: Adding to the recently described individual, our present patient highlights the relevance of movement disorders as a clinically relevant manifestation of KBG syndrome. ANKRD11 pathogenic variants should be considered in the differential diagnosis of combined tremor syndromes.
AU  - Stehr, A.M.*
AU  - Koeglsperger, T.*
AU  - Jacob, M.*
AU  - Rhodio, V.*
AU  - Winkelmann, J.
AU  - Hopfner, F.*
AU  - Zech, M.
C1  - 71872
C2  - 56342
CY  - Unit 3n, 6 Osborn Street, London, E1 6td, England
TI  - Tremor-dominant movement disorder in ANKRD11- associated KBG syndrome.
JO  - Tremor Other Hyperkinet. Mov.
VL  - 14
PB  - Ubiquity Press Ltd
PY  - 2024
SN  - 2160-8288
ER  - 

TY  - JOUR
AB  - Background: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). Case Report: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45. An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of the WDR45 coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls. Discussion: An extended search for deletions should be performed in apparently WDR45-negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.
AU  - Hermann, A.*
AU  - Kitzler, H.H.*
AU  - Pollack, T.*
AU  - Biskup, S.*
AU  - Krüger, S.*
AU  - Funke, C.*
AU  - Terrile, C.
AU  - Haack, T.B.
C1  - 51776
C2  - 43487
TI  - A case of beta-propeller protein-associated neurodegeneration due to a heterozygous deletion of WDR45.
JO  - Tremor Other Hyperkinet. Mov.
VL  - 7
PY  - 2017
SN  - 2160-8288
ER  -