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

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McMacken, Grace 
Lochmüller, Hanns 
Bansagi, Boglarka 
Pyle, Angela 
Lochmüller, Angela 

Abstract: 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.


Funder: Lily Foundation

Funder: Canadian Institutes of Health Research and Muscular Dystrophy Canada

Original Communication, Neurogenetics, Behr syndrome, Hereditary spastic paraplegia, Ataxia, Whole exome sequencing
Journal Title
Journal of Neurology
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Springer Berlin Heidelberg
Newton Fund (MR/N027302/1)
Medical Research Council (MR/N025431/1)
H2020 European Research Council (309548)
Wellcome Trust (201064/Z/16/Z)
Canadian Institutes of Health Research (FDN-167281)
Canadian Foundation for Innovation (CFI-JELF 38412)
Canada Excellence Research Chairs, Government of Canada (950-232279)
Horizon 2020 research and innovation programme (779257)
FP7 Health (305444)