Pathogenic variants in NKX6-2 gene causing autosomal recessive spastic ataxia type 8 with hypomyelinating leukodystrophy have been reported in few families around the world. In this study, we performed Whole Exome Sequencing and identified a novel missense variant, c.501C > G; p.(Phe167Leu), in two affected siblings with main manifestations of global developmental delay, motor regression, hypotonia, clonus in lower limbs and muscle bulk atrophy especially in the upper limbs, spasticity and contracture, scoliosis, hip dislocation, oculomotor apraxia, horizontal and vertical nystagmus. In addition, wrist and foot drop due to peripheral axonal neuropathy were observed in these patients as a new clinical finding and cerebellar white matter involvement in brain Magnetic Resonance Imaging (MRI) as new imaging finding. Therefore, we expanded the manifestations of NKX6-2-related disorders in this manuscript.

NKX6-2中的致病变异在世界上很少有家庭报道过这种基因导致常染色体隐性痉挛性共济失调8型伴低髓性白细胞营养不良。在这项研究中，我们进行了全外显子组测序，并鉴定了一种新型的错义变体，c.501C> G；p。（Phe167Leu），在两个受影响的兄弟姐妹中，主要表现为整体发育迟缓，运动能力下降，肌张力减退，下肢的阵挛和肌肉萎缩，尤其是上肢的肌肉痉挛和挛缩，脊柱侧弯，髋关节脱位，动眼运动性失用，水平和垂直眼球震颤。此外，在这些患者中观察到由于周围轴突神经病引起的手腕和脚下垂是新的临床发现，而脑磁共振成像（MRI）中涉及的小脑白质是新的成像发现。因此，我们扩展了本手稿中的NKX6-2相关疾病。