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 jmedgenet-2020-106896 DO 10.1136/jmedgenet-2020-106896 A1 Toshiyuki Itai A1 Satoko Miyatake A1 Masataka Taguri A1 Fumihito Nozaki A1 Masayasu Ohta A1 Hitoshi Osaka A1 Masafumi Morimoto A1 Tomoko Tandou A1 Fumikatsu Nohara A1 Yuichi Takami A1 Fumitaka Yoshioka A1 Shoko Shimokawa A1 Jiu Okuno-Yuguchi A1 Mitsuo Motobayashi A1 Yuko Takei A1 Tetsuhiro Fukuyama A1 Satoko Kumada A1 Yohane Miyata A1 Chikako Ogawa A1 Yuki Maki A1 Noriko Togashi A1 Teruyuki Ishikura A1 Makoto Kinoshita A1 Yusuke Mitani A1 Yonehiro Kanemura A1 Tsuyoshi Omi A1 Naoki Ando A1 Ayako Hattori A1 Shinji Saitoh A1 Yukihiro Kitai A1 Satori Hirai A1 Hiroshi Arai A1 Fumihiko Ishida A1 Hidetoshi Taniguchi A1 Yasuji Kitabatake A1 Keiichi Ozono A1 Shin Nabatame A1 Robert Smigiel A1 Mitsuhiro Kato A1 Koichi Tanda A1 Yoshihiko Saito A1 Akihiko Ishiyama A1 Yushi Noguchi A1 Mazumi Miura A1 Takaaki Nakano A1 Keiko Hirano A1 Ryoko Honda A1 Ichiro Kuki A1 Jun-ichi Takanashi A1 Akihito Takeuchi A1 Tatsuya Fukasawa A1 Chizuru Seiwa A1 Atsuko Harada A1 Yusuke Yachi A1 Hiroyuki Higashiyama A1 Hiroshi Terashima A1 Tadayuki Kumagai A1 Satoshi Hada A1 Yoshiichi Abe A1 Etsuko Miyagi A1 Yuri Uchiyama A1 Atsushi Fujita A1 Eri Imagawa A1 Yoshiteru Azuma A1 Kohei Hamanaka A1 Eriko Koshimizu A1 Satomi Mitsuhashi A1 Takeshi Mizuguchi A1 Atsushi Takata A1 Noriko Miyake A1 Yoshinori Tsurusaki A1 Hiroshi Doi A1 Mitsuko Nakashima A1 Hirotomo Saitsu A1 Naomichi Matsumoto YR 2020 UL http://jmg.bmj.com/content/early/2020/07/30/jmedgenet-2020-106896.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.