Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Chin Med J (Engl). 2013;126(18):3427-32.
Familial cerebral cavernous malformations (CCMs), characterized by hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular anomalies of the central nervous system. Familial CCMs is an autosomal dominant inherited disorder and three CCM genes have been identified. We report a Chinese family with CCMs and intend to explore clinical, pathological, magnetic resonance imaging (MRI) features and pathogenic gene mutation of this family.
Totally 25 family members underwent brain MRI examination and clinical check. Two patients with surgical indications had surgical treatment and the specimens were subjected to histopathological and microstructural examination. In addition, polymerase chain reaction (PCR) and direct sequencing were performed with genomic DNA extracted from 25 family members' blood samples for mutation detection.
Brain MRI identified abnormal results in seven family members. All of them had multiple intracranial lesions and four cases had skin cavernous hemangioma. T2-weighted sequence showed that the lesions were typically characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence was more sensitive to find micro-cavernous hemangiomas. There was a wide range in the clinical manifestations as well as the age of onset in the family. The youngest patient was an 8-year-old boy with least intracranial lesions. Histopathological and microstructural examination showed that CCMs were typically discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages of illness evolution. They were formed by abnormally enlarged sinusoids and the thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was identified by mutation detection in the seven patients. But unaffected members and healthy controls did not carry this mutation.
The clinical manifestations were heterogenic within this family. We identified a novel mutation (c.1396delT) was the disease-causing mutation for this family and extended the mutational spectrum of CCMs.
家族性脑海绵状血管畸形（CCMs）以出血性卒中、反复发作性头痛和癫痫为特征，是中枢神经系统的先天性血管畸形。家族性 CCM 是一种常染色体显性遗传疾病，已经确定了三个 CCM 基因。我们报告了一个有 CCM 的中国家庭，并旨在探讨这个家庭的临床、病理、磁共振成像（MRI）特征和致病基因突变。
共 25 名家庭成员接受了脑部 MRI 检查和临床检查。两名有手术指征的患者接受了手术治疗，标本进行了组织病理学和微观结构检查。此外，从 25 名家庭成员的血液样本中提取基因组 DNA，进行聚合酶链反应（PCR）和直接测序，以检测突变。
脑部 MRI 在 7 名家庭成员中发现异常结果。他们都有多个颅内病变，4 例有皮肤海绵状血管瘤。T2 加权序列显示病变典型特征为混合信号强度区域。梯度回波（GRE）序列对发现微海绵状血管瘤更敏感。家族中有广泛的临床表现和发病年龄。最小的患者是一名 8 岁男孩，颅内病变最少。组织病理学和微观结构检查显示，CCMs 典型地为离散的多小叶状浆果样病变，具有不同疾病演变阶段的出血。它们由异常扩大的窦和薄的基底膜形成。通过对 7 名患者的突变检测，发现 CCM1 基因第 14 外显子的一个新的 T 缺失突变。但未受影响的成员和健康对照者没有携带这种突变。
这个家庭的临床表现具有异质性。我们确定了一个新的突变（c.1396delT）是这个家庭的致病突变，并扩展了 CCM 的突变谱。
