Background

The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic conditions in humans, including the brain, eyes, kidneys, muscles, and other organs at any age. Brain imaging shows a wide spectrum of abnormalities, including porencephaly, schizencephaly, polymicrogyria focal cortical dysplasia, periventricular leukoencephalopathy, ventricular dysmorphisms, and multiple brain calcifications. However, there are no reports in the literature showing progressive radiological findings in consecutive follow-up scans. Herein, we report three cases of COL4A1 mutations with porencephaly from gestation to five years of age or longer, and describe their clinical and brain imaging findings.

Case reports: We retrospectively reviewed the clinical symptoms and radiological findings, including brain magnetic resonance imaging (MRI) and computed tomography (CT), in three female patients with COL4A1 mutations. Their mutations were c.4843G>A (p.Glu1615Lys), c.1835G>A (p.Gly612Asp), and c.3556+1G>T respectively. All the three cases represented porencephaly in the fetal period; severe hemolytic anemia in the neonatal period; and drug-resistant epilepsy, global developmental delay, and spastic quadriplegia in their childhood.

Results

Brain MRI and CT showed progressive white matter atrophy from gestation to five-year follow-up or later. Minor cerebral hemorrhage without symptoms occasionally occurred in one patient. Despite brain changes, the clinical picture was stable during early childhood.

Conclusions

COL4A1 mutations may cause progressive cerebral atrophy beyond early childhood.

中文翻译：

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三名 COL4A1 突变儿童进行性脑萎缩

背景

13q34 上的 IV 型胶原蛋白α 1 链 ( COL4A1 ) 基因编码一条胶原蛋白链。COL4A1突变已被确定为人类一组多系统疾病的原因，包括任何年龄的大脑、眼睛、肾脏、肌肉和其他器官。脑成像显示广泛的异常，包括孔脑畸形、裂脑畸形、多小脑回局灶性皮质发育不良、脑室周围白质脑病、心室畸形和多发性脑钙化。然而，文献中没有报告显示连续随访扫描中进行性放射学检查结果。在此，我们报告了三例COL4A1从妊娠到 5 岁或更长的时间与 porencephaly 突变，并描述他们的临床和脑成像发现。

病例报告：我们回顾性回顾了三名COL4A1突变女性患者的临床症状和放射学检查结果，包括脑磁共振成像 (MRI) 和计算机断层扫描 (CT) 。它们的突变分别为c.4843G>A（p.Glu1615Lys）、c.1835G>A（p.Gly612Asp）和c.3556+1G>T。这三个病例都代表胎儿期的前脑畸形；新生儿期严重溶血性贫血; 以及儿童时期的耐药性癫痫、全球发育迟缓和痉挛性四肢瘫痪。

结果

脑 MRI 和 CT 显示从妊娠到 5 年随访或更晚的随访期间白质进行性萎缩。1例患者偶有无症状轻微脑出血。尽管大脑发生了变化，但临床表现在儿童早期是稳定的。

结论

COL4A1突变可能导致超越儿童早期的进行性脑萎缩。