Department of Neurosciences, Royal Victoria Hospital, Belfast, UK.
Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany.
J Neurol. 2020 Dec;267(12):3643-3649. doi: 10.1007/s00415-020-10059-3. Epub 2020 Jul 12.
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.
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.
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.
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.
Behr 综合征是一种临床表现独特但遗传异质性的疾病，其特征为视神经萎缩、进行性痉挛性截瘫和运动神经病，常伴有共济失调。分子诊断基于基因组合测试或外显子组/基因组测序。
本研究报道了两例具有新型 Behr 综合征遗传形式的同胞的临床表现。我们对两名患者及其母亲进行了全外显子组测序。
两名患者均有儿童期起病、缓慢进展的疾病，类似于 Behr 综合征，首发症状为视力损害，随后出现进行性痉挛、下肢无力和萎缩以及共济失调。他们还出现了脊柱侧凸，导致呼吸问题。在 30 多岁时，两名患者均发展为肥厚型心肌病，并分别在 43 岁和 40 岁时因心脏性猝死而死亡。全外显子组测序发现 UCHL1 中 c.627_629del;p.(Gly210del) 新型纯合缺失。
我们患者的临床表现提示肥厚型心肌病可能是与 UCHL1 突变相关的临床综合征的另一特征，并强调了在与 UCHL1 突变相关的神经退行性疾病中进行心脏随访和治疗的重要性。
