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.

中文翻译：

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具有新型 UCHL1 缺失的家族中的 Behr 综合征和肥厚性心肌病。

背景

Behr 综合征是一种临床上不同但遗传异质的疾病，其特征是视神经萎缩、进行性痉挛性截瘫和运动神经病变，通常与共济失调有关。分子诊断基于基因组测试或全外显子组/基因组测序。

方法

在这里，我们报告了两个兄弟姐妹的临床表现，这些兄弟姐妹患有一种新的 Behr 综合征遗传形式。我们对两名患者及其母亲进行了全外显子组测序。

结果

两名患者都患有类似于 Behr 综合征的儿童期发病缓慢进展性疾病，首先是视力障碍，然后是进行性痉挛、虚弱和小腿萎缩和共济失调。他们还患上脊柱侧弯，导致呼吸系统问题。在他们 30 多岁的时候，两个兄弟姐妹都患上了肥厚型心肌病，并分别在 43 岁和 40 岁时死于心源性猝死。全外显子组测序鉴定出新的纯合 c.627_629del；UCHL1中的 p.(Gly210del) 缺失。

结论

我们患者的表现提出了肥厚型心肌病可能是与UCHL1突变相关的临床综合征的附加特征的可能性，并强调了心脏随访和治疗在与UCHL1突变相关的神经退行性疾病中的重要性。