Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Eur Rev Med Pharmacol Sci. 2024 Feb;28(4):1605-1609. doi: 10.26355/eurrev_202402_35489.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominantly inherited cerebral small vessel disease caused by Neurogenic locus notch homolog protein 3 (NOTCH3) gene mutations. The main clinical features include migraine with aura, recurrent ischemic strokes and dementia. Brain MRI typically shows multiple small lacunar infarcts and severe, diffuse, symmetrical white matter hyperintensities (WMHs), with characteristic involvement of the anterior temporal pole, external capsule, and superior frontal gyrus. Reports of twins with CADASIL are scarce. Herein we describe a pair of monozygotic twins with peculiar CADASIL phenotype, carrying a new NOTCH3 variant.
Twin A was a 45-year-old male suffering from migraine, obesity, arterial hypertension, and polycythemia (with negative genetic analysis), who complained of a transient, short-lasting (~ 5 minutes) episode of speech difficulties. Brain MRI showed diffuse, symmetrical, confluent periventricular WMHs involving frontal, parietal, and temporal lobes and external capsules, with sparing of anterior temporal poles. Genetic analysis of NOTCH3 gene demonstrated the presence of missense c.3329G>A, p.(Cys1110Tyr) variant, confirming CADASIL diagnosis. Twin B, affected by migraine and polycythemia, as well as his monozygotic twin, presented with a 2-month history of trigeminal neuralgia. Brain MRI demonstrated diffuse WMHs with a pattern of distribution like his twin. Genetic analysis revealed the same NOTCH3 pathogenic variant.
Our monozygotic twins have a strikingly similar neuroimaging picture with sparing of anterior temporal poles. They also have a peculiar phenotype, both presenting polycythemia without genetically confirmed cause. Twin B had trigeminal neuralgia, that is unusual in CADASIL. The possible association of the peculiar findings with the newly reported NOTCH3 variant needs to be confirmed with further observations.
伴有皮质下梗死和白质脑病的脑常染色体显性遗传性动脉病（CADASIL）是一种常染色体显性遗传性脑小血管病，由神经源性同源异型蛋白 3（NOTCH3）基因突变引起。主要的临床特征包括有先兆偏头痛、复发性缺血性卒中和痴呆。脑 MRI 通常显示多发性腔隙性梗死和严重、弥漫、对称的脑白质高信号（WMHs），特征性地累及前颞极、外囊和额上回。CADASIL 双胞胎的报道很少。在此，我们描述了一对具有特殊 CADASIL 表型的同卵双胞胎，携带新的 NOTCH3 变异。
双胞胎 A 是一名 45 岁男性，患有偏头痛、肥胖、动脉高血压和红细胞增多症（基因分析阴性），他抱怨短暂、短暂发作（约 5 分钟）的言语困难。脑 MRI 显示弥漫性、对称性、融合性脑室周围 WMHs，累及额、顶和颞叶及外囊，前颞极不受累。NOTCH3 基因突变分析显示存在错义 c.3329G>A，p.（Cys1110Tyr）变异，确诊 CADASIL。双胞胎 B 患有偏头痛和红细胞增多症，以及他的同卵双胞胎，出现了 2 个月的三叉神经痛病史。脑 MRI 显示弥漫性 WMHs，分布模式与他的双胞胎相似。基因突变分析显示存在相同的 NOTCH3 致病性变异。
我们的同卵双胞胎具有惊人相似的神经影像学图像，前颞极不受累。他们还具有特殊的表型，都有红细胞增多症，但没有遗传证实的原因。双胞胎 B 患有三叉神经痛，这在 CADASIL 中不常见。这些特殊发现与新报告的 NOTCH3 变异的可能关联需要进一步观察来证实。
