Published Ahead of Print on May 26, 2021 as 10.1212/WNL.0000000000012264

Neurology Publish Ahead of Print DOI: 10.1212/WNL.0000000000012264

Teaching Video NeuroImages: New STUB1 Variant Causes Chorea, , , , , Depression, Cognitive Impairment, , and Superficial Siderosis

Carsten Saft1, Sabine Skodda2, Huu Phuc Nguyen3, Joohyun Park4, Tobias B Haack4

Affiliations:

1 Department of , Huntington-Centre NRW, St. Josef Hospital, Bochum, Germany

2Department of Neurology, Knappschaftskrankenhaus, Bochum, Germany

3Department of Human Genetics, Ruhr-University of Bochum, Bochum, Germany

4Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany

Corresponding Author: Dr. Saft [email protected].

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Word count

• A title of 139 characters (including spaces and punctuation) • A legend of 52 words and a figure legend of 58 words • A case summary of 119 words • 2 references

Figures: 1

Tables: 0

Videos: 1

Study Funding: The authors report no targeted funding

Disclosure:

C Saft reports no disclosures relevant to the manuscript

S Skodda reports no disclosures relevant to the manuscript

HP Nguyen reports no disclosures relevant to the manuscript

J Park reports no disclosures relevant to the manuscript

TB Haack reports no disclosures relevant to the manuscript

Case Summary

We present a family with a wide range of movement disorders carrying a new heterozygous splice variant in STUB1 (NM_005861:c.787-2_787del), probably causing skipping of exon 7, as relevant differential diagnosis to Huntington’s disease. Grandmother and mother (improved with olanzapine) presented with chorea, dystonia (also platysma), head-tremor, orofacial (prior to neuroleptics), saccadic eye movements, ataxia with cerebellar atrophy (see figure 1), depression, cachexia and cognitive impairment. The grandmother suffered from epilepsy and mother from superficial siderosis (see figure 1). The son presented with depression, left sided myoclonus and ataxia, and tremor resembling which began in childhood without alcohol sensitivity. STUB1 mutation in this family caused chorea, tremor, dystonia, myoclonus, ataxia, depression, cognitive impairment, epilepsy and superficial siderosis (see video 1,http://links.lww.com/WNL/B433).

Legend video 1

Grandmother (age at onset (AO): 63, died age 65 years (pulmonary embolism), epilepsy since age 55 years)); mother (AO: 49, died age 52 years (reason unclear)) and son (age 31 years,

Copyright © 2021 American Academy of Neurology. Unauthorized reproduction of this article is prohibited AO: childhood) with various movement disorders. Exclusion of Huntington’s disease, SCA 1-3, 6, 7, 12, 17, DRPLA, FXTAS, C9orf72, NBIA mutation.

Legend figure 1

T2-weighted MRI (a-c) of the grandmother showing cerebellar atrophy (a,b) and hypointensity (with no correlate in cerebral computed tomography; c; see arrow). T2- weighted and SWI weighted MRI of the mother (d-f) showing cerebellar atrophy (d) and basal ganglia SWI artifacts (e; see arrow) and cortical SWI artifacts highly suggestive of superficial siderosis (f; see arrows).

References

1. Clinical, neuropathological, and genetic characterization of STUB1 variants in cerebellar : a frequent cause of predominant cognitive impairment. Roux T, Barbier M, Papin M, Davoine CS, Sayah S, Coarelli G, Charles P, Marelli C, Parodi L, Tranchant C, Goizet C, Klebe S, Lohmann E, Van Maldergen L, van Broeckhoven C, Coutelier M, Tesson C, Stevanin G, Duyckaerts C, Brice A, Durr A; SPATAX network. Genet Med. 2020 Nov;22(11):1851-1862. 2. type 48: last but not least. De Michele G, Galatolo D, Barghigiani M, Dello Iacovo D, Trovato R, Tessa A, Salvatore E, Filla A, De Michele G, Santorelli FM. Neurol Sci. 2020 Sep;41(9):2423-2432.

Copyright © 2021 American Academy of Neurology. Unauthorized reproduction of this article is prohibited Teaching Video NeuroImages: New STUB1 Variant Causes Chorea, Tremor, Dystonia, Myoclonus, Ataxia, Depression, Cognitive Impairment, Epilepsy, and Superficial Siderosis Carsten Saft, Sabine Skodda, Huu Phuc Nguyen, et al. Neurology published online May 26, 2021 DOI 10.1212/WNL.0000000000012264

This information is current as of May 26, 2021

Updated Information & including high resolution figures, can be found at: Services http://n.neurology.org/content/early/2021/05/26/WNL.0000000000012264. citation.full Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Chorea http://n.neurology.org/cgi/collection/chorea Huntington's disease http://n.neurology.org/cgi/collection/huntingtons_disease Myoclonus http://n.neurology.org/cgi/collection/myoclonus Spinocerebellar ataxia http://n.neurology.org/cgi/collection/spinocerebellar_ataxia Tremor http://n.neurology.org/cgi/collection/tremor Permissions & Licensing Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/about/about_the_journal#permissions Reprints Information about ordering reprints can be found online: http://n.neurology.org/subscribers/advertise

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