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Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion

Lookup NU author(s): Dr Grace McMacken, Professor Hanns Lochmuller, Dr Boglarka Bansagi, Dr Angela Pyle, Professor Patrick Chinnery, Professor Rita HorvathORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020, The Author(s).Background: Behr syndrome is a clinically distinct, but genetically heterogeneous disorder characterized by optic atrophy, progressive spastic paraparesis, and motor neuropathy often associated with ataxia. The molecular diagnosis is based on gene panel testing or whole-exome/genome sequencing. Methods: Here, we report the clinical presentation of two siblings with a novel genetic form of Behr syndrome. We performed whole-exome sequencing in the two patients and their mother. Results: Both patients had a childhood-onset, slowly progressive disease resembling Behr syndrome, starting with visual impairment, followed by progressive spasticity, weakness, and atrophy of the lower legs and ataxia. They also developed scoliosis, leading to respiratory problems. In their late 30’s, both siblings developed a hypertrophic cardiomyopathy and died of sudden cardiac death at age 43 and 40, respectively. Whole-exome sequencing identified the novel homozygous c.627_629del; p.(Gly210del) deletion in UCHL1. Conclusions: The presentation of our patients raises the possibility that hypertrophic cardiomyopathy may be an additional feature of the clinical syndrome associated with UCHL1 mutations, and highlights the importance of cardiac follow-up and treatment in neurodegenerative disease associated with UCHL1 mutations.

Publication metadata

Author(s): McMacken G, Lochmuller H, Bansagi B, Pyle A, Lochmuller A, Chinnery PF, Laurie S, Beltran S, Matalonga L, Horvath R

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2020

Volume: 267

Issue: 12

Pages: 3643-3649

Print publication date: 01/12/2020

Online publication date: 12/07/2020

Acceptance date: 04/07/2020

Date deposited: 26/07/2021

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer Science and Business Media Deutschland GmbH


DOI: 10.1007/s00415-020-10059-3

PubMed id: 32656641


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Funder referenceFunder name
201064/Z/16/ZWellcome Trust
109915/Z/15/ZWellcome Trust
779257European Commission
CFI-JELF 38412
MR/N025431/1Medical Research Council (MRC)
MR/N027302/1Medical Research Council (MRC)