Cortical malformations and COL4A1 mutation: Three new cases.

AIM: The COL4A1 gene (13q34) encodes the α1 chain of type IV collagen, a crucial component of the basal membrane. COL4A1 mutations have been identified as a cause of a multisystem disease. Brain MRI in COL4A1-mutated patients typically shows vascular abnormalities and white matter lesions. Cortical malformations (specifically schizencephaly) have also recently been described in these patients, suggesting that these, too, could be part of the phenotypic spectrum of COL4A1 mutations. The aim of our work was to retrospectively evaluate COL4A1-mutated subjects diagnosed at our centers in order to assess the frequency and define the type of cortical malformations encountered in these individuals. METHOD: We retrospectively reviewed MRI data of 18 carriers of COL4A1 mutations diagnosed in our centers between 2010 and 2016. RESULTS: We identified polymicrogyria in two patients, and schizencephaly in the mother of a further patient. INTERPRETATION: Our findings confirm that cortical malformations should be considered to fall within the phenotypic spectrum of COL4A1 mutations and show that not only schizencephaly but also polymicrogyria can also be found in mutated individuals. Although further studies are needed to clarify the underlying pathogenetic mechanism, independently of this, the timing of the brain damage could be the crucial factor determining the type of lesion.

COL4A1 mutations associated with a characteristic pattern of intracranial calcification.

Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign.From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found.All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T2 and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons.ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutiéres syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radio-logical findings should suggest the possibility of COL4A1-related disease.