Mutations in apoptosis‐inducing factor mitochondrion‐associated‐1 (AIFM1) cause X‐linked peripheral neuropathy (Cowchock syndrome, CMT4X); however, more recently a cerebellar presentation has been described. We describe a large Irish family with seven affected males. They presented with a variable age of onset, 18 months to 39 years of age. All developed variably present sensorineural deafness, peripheral neuropathy, cerebellar ataxia, and pyramidal involvement. In addition, three had colour vision deficiency. Scale for the assessment and rating of ataxia ranged 2 to 23/40, while Charcot‐Marie‐Tooth neuropathy score 2 varied between 7 and 13/36. All individuals had normal cognitive assessment. Neurophysiology demonstrated length‐dependent large‐fibre sensorimotor axonal neuropathy, with particular involvement of superficial radial sensory responses. Brain imaging, performed in four, revealed varying extent of cerebellar atrophy, and white matter changes in one. Optical coherence tomography was abnormal in one, who had unrelated eye pathology. Four obligate female carriers were assessed clinically, two of them neurophysiologically; all were unaffected. Whole genome sequencing demonstrated a previously reported hemizygous AIFM1 mutation. Analysis for mutations in other genes associated with colour deficiency was negative. AIFM1‐associated phenotype in this family demonstrated significant variability. To our knowledge, this is the first report of AIFM1‐associated colour blindness. Superficial radial nerve was particularly affected neurophysiologically, which could represent a phenotypic marker towards this specific genetic diagnosis.

中文翻译：

---

爱尔兰家庭中与AIFM1相关的疾病的临床范围，从轻度神经病变到严重的小脑共济失调和色盲。

凋亡诱导因子线粒体相关1（AIFM1）的突变）引起X连锁性周围神经病变（考克斯综合征，CMT4X）；然而，最近已经描述了小脑表现。我们描述了一个爱尔兰大家庭，其中有7位受影响的男性。他们的发病年龄可变，为18个月至39岁。所有进展的患者均表现为感音神经性耳聋，周围神经病变，小脑共济失调和锥体束受累。另外，三人有色觉不足。共济失调的评估和评定量表范围为2到23/40，而Charcot-Marie-Tooth神经病评分2在7到13/36之间变化。所有个体的认知评估都正常。神经生理学证明了长度依赖性的大纤维感觉运动轴突神经病，特别是涉及浅表radial感觉反应。脑成像，四次进行，揭示了小脑萎缩的程度不同，其中之一是白质改变。一位患者的光学相干断层扫描异常，其眼睛病理学无关。临床上评估了四种专性女性携带者，其中两种是神经生理学的。都没有受到影响。全基因组测序证明以前报道过的半合子AIFM1突变。与颜色缺乏相关的其他基因突变的分析为阴性。该家族中与AIFM1相关的表型表现出显着的变异性。据我们所知，这是AIFM1相关色盲的首次报道。浅radial神经在神经生理学上受到特别的影响，这可能代表了这种特定遗传诊断的表型标记。