BACKGROUND Perrault syndrome is a genetically heterogenous, very rare disease, characterized clinically by sensorineural hearing loss, ovarian dysfunction and neurological symptoms. We present the case of a 33 years old female patient with TWNK-associated Perrault syndrome. The TWNK gene is coding the mitochondrial protein Twinkle and currently there are only two reports characterizing the phenotype of TWNK-associated Perrault syndrome. None of these publications reported about special brain MRI alterations and neuropathological changes in the muscle and peripheral nerves. CASE PRESENTATION Our patients with TWNK-dependent Perrault syndrome had severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis. Psychiatric symptoms such as depression and paranoia were present as well. Brain MRI observed progressive cerebellar hyperintensive signs associated with cerebellar, medulla oblongata and cervical spinal cord atrophy. Light microscopy of the muscle biopsy detected severe neurogenic lesions. COX staining was centrally reduced in many muscle fibers. Both muscle and sural nerve electron microscopy detected slightly enlarged mitochondria with abnormal cristae surrounded by lipid vacuoles. In the sural nerve, dystrophic axons had focally uncompacted myelin lamellae present. Genetic investigation revealed multiple mtDNA deletion and compound heterozygous mutations of the TWNK gene (c.1196 A > G, c.1358 G > A). CONCLUSION This study demonstrates that TWNK associated Perrault syndrome has a much broader phenotype as originally published. The coexistence of severe hypoacusis, spastic limb weakness, ataxia, polyneuropathy, gonadal dysgensia, hyperintense signals in the cerebellum and the presence of the mtDNA multiple deletion could indicate the impairment of the TWNK gene. This is the first report about pyramidal tract involvement and cerebellar MRI alteration associated with TWNK-related Perrault syndrome.

中文翻译：

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拓宽TWNK基因相关的Perrault综合征的表型。

背景技术Perrault综合征是遗传上异质的非常罕见的疾病，临床上以感觉神经性听力丧失，卵巢功能障碍和神经系统症状为特征。我们介绍了一名与TWNK相关的Perrault综合征的33岁女性患者的病例。TWNK基因编码线粒体蛋白“闪烁”，目前只有两个报道描述TWNK相关的Perrault综合征的表型。这些出版物都没有报道过特殊的大脑MRI改变以及肌肉和周围神经的神经病理学改变。病例介绍我们的TWNK依赖型Perrault综合征患者患有严重的双侧视神经错觉，严重的共济失调，多发性神经病，下肢痉挛性截瘫并伴有锥体束征和性腺发育不全。也出现精神症状，如抑郁和妄想症。脑部MRI观察到与小脑，延髓和颈脊髓萎缩有关的进行性小脑高血脂体征。肌肉活检的光学显微镜检测到严重的神经源性病变。在许多肌肉纤维中，COX染色被集中减少。肌肉和腓肠神经电镜均检测到线粒体轻度增大，ista部被脂质液泡包围。在腓肠神经中，营养不良的轴突存在局灶性未致密化的髓鞘片。遗传研究显示TWNK基因有多个mtDNA缺失和复合杂合突变（c.1196 A> G，c.1358 G> A）。结论这项研究表明TWNK相关的Perrault综合征具有比最初发表的广泛得多的表型。严重的轻度听觉减退，肢体痉挛痉挛，共济失调，多发性神经病，性腺发育不全，小脑高信号和并发mtDNA多重缺失并存可能表明TWNK基因受损。这是有关与TWNK相关的Perrault综合征相关的锥体束受累和小脑MRI改变的首次报道。