Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3
Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3
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DOI：
10.1007/s00381-014-2589-y
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发表时间：
2015-03-01
影响因子：
1.4
通讯作者：
Yamasaki, Mami
中科院分区：
文献类型：
--
作者：
Harada, Atsuko;Miya, Fuyuki;Yamasaki, Mami
巨脑毛细血管畸形（MCAP）是一种涉及脑过度生长的综合征，其特征在于巨脑畸形、毛细血管畸形、不对称生长、多小脑回、多指和并指。小脑扁桃体疝（CTH）和脑室扩大也观察到超过一半的患者与这种综合征。早期猝死已被报道在MCAP，但其原因和手术策略，以防止其仍然不清楚。在这里，我们报告的病人与MCAP谁突然死亡，在5个月大。他表现为进行性大头畸形和张力减退。在4个月大时进行的MRI显示后颅窝变紧，双侧侧裂周多小脑回，直窦扩大，胼胝体增厚。然而，由于患者未表现出毛细血管畸形、多指或并指，因此无法明确诊断MCAP。一个月后，他在家中睡觉时突然死亡。MCAP患者的猝死先前归因于CTH、惊厥或心律失常。在这个病例中，进行性小脑增大似乎是根本原因。病人死后，利用他保存的DNA，AKT 3基因中的错义突变被鉴定出来。Vakt小鼠胸腺瘤病毒癌基因同源物（AKT）是一种丝氨酸-苏氨酸激酶，在哺乳动物雷帕霉素靶蛋白（mTOR）通路中发挥作用，在细胞增殖中起重要作用，早期准确诊断包括影像学和遗传学分析，以及识别和治疗危急情况，以防止MCAP患者的猝死。
Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear.Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation.Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.