Introduction

Kabuki syndrome (KS) and spinocerebellar ataxia (SCA) are both rare conditions with neurodevelopmental abnormalities. Approaching a patient with complex phenotypes and differentiating the role of mutations may be beneficial but challenging in predicting the disease prognosis.

Case presentation

A boy presented with progressive ataxia, developmental regression, and myoclonus since 4 years of age. Additional features included growth hormone deficiency, excessive body hair, dysmorphic facies, hypoparathyroidism, and bilateral sensorineural hearing impairment. Brain magnetic resonance imaging depicted T2-weighted hyperintensities over bilateral globus pallidus, thalamus, subcortical white matter, and brainstem. The results of tandem mass spectrometry, mitochondrial deletion, and mitochondrial DNA sequencing were inconclusive. Whole-exome sequencing (WES) on genomic DNA obtained from peripheral blood cells revealed a known pathogenic variant at KMT2D gene (c.5993A > G, p.Tyr1998Cys) related to KS and two compound heterozygous, likely pathogenic variants at VPS13D gene (c.908G > A, p.Arg303Gln and c.8561T > G, p.Leu2854Arg) related to autosomal recessive SCA type 4 (SCAR4).

Discussion

SCAR4 is mainly adult-onset, but a few pediatric cases have recently been reported with progressive gait instability and developmental delay. The VPS13D gene has been suggested to play a role in mitochondrial size, autophagy, and clearance, thus explaining the clinical and imaging phenotypes.

Conclusion

Our case showed a rare co-existence of KS and SCAR4, highlighting the utility of WES in atypical cases that a single-gene disease cannot fully explain.

中文翻译：

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一名患有进行性神经功能衰退的男孩，携带 KMT2D 和 VPS13D 两种共存突变

介绍

歌舞伎综合征 (KS) 和脊髓小脑性共济失调 (SCA) 都是罕见的神经发育异常疾病。接近具有复杂表型的患者并区分突变的作用可能是有益的，但在预测疾病预后方面具有挑战性。

案例展示

一名男孩自 4 岁起出现进行性共济失调、发育退化和肌阵挛。其他特征包括生长激素缺乏、体毛过多、面部畸形、甲状旁腺功能减退和双侧感音神经性听力障碍。脑磁共振成像显示双侧苍白球、丘脑、皮质下白质和脑干出现 T2 加权高信号。串联质谱、线粒体缺失和线粒体DNA测序的结果尚无定论。对从外周血细胞获得的基因组 DNA进行全外显子组测序 (WES)揭示了与 KS 相关的KMT2DVPS13D基因 (c.5993A > G, p.Tyr1998Cys) 的两个复合杂合可能致病性变异.908G > A，p.Arg303Gln 和 c.8561T > G，p.Leu2854Arg) 与常染色体隐性 SCA 4 型 (SCAR4) 相关。

讨论

SCAR4 主要是成人发病，但最近报道了一些儿童病例，伴有进行性步态不稳定和发育迟缓。VPS13D基因被认为在线粒体大小、自噬和清除中发挥作用，从而解释了临床和影像表型。

结论

我们的病例显示 KS 和 SCAR4 罕见地共存，凸显了 WES 在单基因疾病无法完全解释的非典型病例中的效用。