Blumkin Lubov, Leshinsky-Silver Esther, Michelson Marina, Zerem Ayelet, Kivity Sara, Lev Dorit, Lerman-Sagie Tally
Pediatric Neurology Unit, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Molecular Laboratory, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
Eur J Paediatr Neurol. 2015 May;19(3):292-7. doi: 10.1016/j.ejpn.2014.12.018. Epub 2015 Jan 8.
Paroxysmal tonic upward gaze was initially described as a benign phenomenon with negative investigations and eventual complete resolution of symptoms. Later publications demonstrated that a similar clinical picture may arise from structural brain lesions, channelopathies, neurotransmitter disorders, and epileptic seizures. CACNA1A related disorders manifest as a wide spectrum of paroxysmal neurological disorders: episodic ataxia 2, hemiplegic migraine, benign paroxysmal torticollis of infancy, and paroxysmal vertigo. Paroxysmal tonic upward gaze as a phenomenon in patients with mutations in the CACNA1A gene has only been reported once.
We describe three patients with multiple episodes of paroxysmal tonic upward gaze that appeared during the first months of life. In addition the patients demonstrated motor and language delay and cerebellar ataxia. A sequence analysis of the CACNA1A gene in one patient and whole exome sequencing in the other patients were performed.
Sequence analysis of the CACNA1A gene in one patient and whole exome sequencing in the two other patients revealed 3 different de-novo mutations in the CACNA1A gene.
CACNA1A mutations should be evaluated in infants and young children with paroxysmal tonic upgaze especially if associated with developmental delay, cerebellar signs, and other types of paroxysmal event.
阵发性强直性上视最初被描述为一种良性现象，检查结果为阴性，症状最终完全缓解。后来的文献表明，类似的临床表现可能由脑结构病变、离子通道病、神经递质紊乱和癫痫发作引起。与CACNA1A相关的疾病表现为广泛的阵发性神经系统疾病：发作性共济失调2型、偏瘫性偏头痛、婴儿良性阵发性斜颈和阵发性眩晕。作为CACNA1A基因突变患者中的一种现象，阵发性强直性上视仅被报道过一次。
我们描述了3例在生命最初几个月出现多次阵发性强直性上视发作的患者。此外，这些患者还表现出运动和语言发育迟缓以及小脑共济失调。对1例患者进行了CACNA1A基因序列分析，对其他患者进行了全外显子组测序。
1例患者的CACNA1A基因序列分析以及另外2例患者的全外显子组测序显示，CACNA1A基因存在3种不同的新发突变。
对于出现阵发性强直性上视的婴幼儿，尤其是伴有发育迟缓、小脑体征和其他类型阵发性事件的患者，应评估其CACNA基因突变情况。
