RT Journal Article SR Electronic T1 Prenatal clinical manifestations in individuals with COL4A1/2 variants JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 505 OP 513 DO 10.1136/jmedgenet-2020-106896 VO 58 IS 8 A1 Itai, Toshiyuki A1 Miyatake, Satoko A1 Taguri, Masataka A1 Nozaki, Fumihito A1 Ohta, Masayasu A1 Osaka, Hitoshi A1 Morimoto, Masafumi A1 Tandou, Tomoko A1 Nohara, Fumikatsu A1 Takami, Yuichi A1 Yoshioka, Fumitaka A1 Shimokawa, Shoko A1 Okuno-Yuguchi, Jiu A1 Motobayashi, Mitsuo A1 Takei, Yuko A1 Fukuyama, Tetsuhiro A1 Kumada, Satoko A1 Miyata, Yohane A1 Ogawa, Chikako A1 Maki, Yuki A1 Togashi, Noriko A1 Ishikura, Teruyuki A1 Kinoshita, Makoto A1 Mitani, Yusuke A1 Kanemura, Yonehiro A1 Omi, Tsuyoshi A1 Ando, Naoki A1 Hattori, Ayako A1 Saitoh, Shinji A1 Kitai, Yukihiro A1 Hirai, Satori A1 Arai, Hiroshi A1 Ishida, Fumihiko A1 Taniguchi, Hidetoshi A1 Kitabatake, Yasuji A1 Ozono, Keiichi A1 Nabatame, Shin A1 Smigiel, Robert A1 Kato, Mitsuhiro A1 Tanda, Koichi A1 Saito, Yoshihiko A1 Ishiyama, Akihiko A1 Noguchi, Yushi A1 Miura, Mazumi A1 Nakano, Takaaki A1 Hirano, Keiko A1 Honda, Ryoko A1 Kuki, Ichiro A1 Takanashi, Jun-ichi A1 Takeuchi, Akihito A1 Fukasawa, Tatsuya A1 Seiwa, Chizuru A1 Harada, Atsuko A1 Yachi, Yusuke A1 Higashiyama, Hiroyuki A1 Terashima, Hiroshi A1 Kumagai, Tadayuki A1 Hada, Satoshi A1 Abe, Yoshiichi A1 Miyagi, Etsuko A1 Uchiyama, Yuri A1 Fujita, Atsushi A1 Imagawa, Eri A1 Azuma, Yoshiteru A1 Hamanaka, Kohei A1 Koshimizu, Eriko A1 Mitsuhashi, Satomi A1 Mizuguchi, Takeshi A1 Takata, Atsushi A1 Miyake, Noriko A1 Tsurusaki, Yoshinori A1 Doi, Hiroshi A1 Nakashima, Mitsuko A1 Saitsu, Hirotomo A1 Matsumoto, Naomichi YR 2021 UL http://jmg.bmj.com/content/58/8/505.abstract AB Background Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.Methods We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.Results Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.Conclusions Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.All data relevant to the study are included in the article or uploaded as supplementary information. Additional material is published online only. To view, please visit the journal online.