Rare homozygous nonsense variant in AIMP1 causing Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS)
Rare homozygous nonsense variant in AIMP1 causing Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS)
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DOI：
10.1016/j.ejmg.2020.103970
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发表时间：
2020-09-01
影响因子：
1.9
通讯作者：
Segal, Eric
中科院分区：
文献类型：
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作者：
Gupta, Siddharth;Schwab, Maria;Segal, Eric
AIMP 1基因的致病性变异是神经系统疾病的罕见原因。在严重的神经退行性疾病中已经描述了AIMP 1中的纯合移码和无义变体。这是第三个报告的纯合子无义变异AIMP 1 [c.115 C > T（p.Gln39*）]在一个女孩与严重的新生儿发作癫痫性脑病。与其他两例报告一样，我们的患者也是菲律宾裔。临床特征包括小头畸形、视觉运动发育不良、浅呼吸、四肢严重张力亢进、严重全身发育迟缓、呕吐和吸吮反射不良、新生儿期发育不良和早发性顽固性癫痫发作。脑部MRI显示胼胝体和小脑蚓部发育不全，整体体积损失和髓鞘形成减少。4个月龄时的脑电图显示背景由爆发抑制的同步和异步间隔组成，间歇性多灶性棘波主要位于双颞区，提示早发性癫痫性脑病伴爆发抑制（EOEE-BS），其先前与AIMP 1中的c.115 C > T变体无关。值得注意的是，她向我们介绍了超难治性癫痫持续状态，在给予生酮饮食和Epidiolex（大麻二酚）后最终得到控制。本报告扩展了EOEEBS的遗传景观。这是第一例给予Epidiolex的这种特定变体的病例，Epidiolex与生酮饮食一起沿着有助于控制患者的超难治性癫痫持续状态。
Pathogenic variants in AIMP1 gene are rare causes of neurologic disorders. Homozygous frameshift and nonsense variants in AIMP1 have been described in severe neurodegenerative disease. This is the third report of a homozygous nonsense variant in AIMP1 [c.115 C > T (p.Gln39*)] in a girl with severe neonatal onset epileptic encephalopathy. Like the two other cases reported, our patient is also of Filipino descent. Clinical features include microcephaly, poor visual motor development, shallow breathing, severe hypertonia in extremities, severe global developmental delay, poor gag and suck reflex, failure to thrive in the neonatal period, and early onset intractable seizures. Brain MRI showed hypoplasia of corpus callosum as well as cerebellar vermis, global volume loss and diminished myelination for her age. Electroencephalogram at four months of age showed background consisting of synchronous and asynchronous intervals of burst suppression with intermittent multifocal spikes predominantly in the bi-temporal region, suggestive of Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS) which has not been previously associated with the c.115 C > T variant in AIMP1. Of note, she presented to us in super refractory status epilepticus which was eventually controlled after administration of ketogenic diet and Epidiolex (cannabidiol). This report expands the genetic landscape of EOEEBS. This is the first case of this specific variant in which Epidiolex was administered, which along with Ketogenic diet aided in controlling patient's super refractory status epilepticus.