J Neurosurg: Pediatrics / Volume 8 / October 2011 J Neurosurg Pediatrics 8:000–000, 2011 411 C ongenital hydrocephalus is one of the most com- mon and serious developmental malformations treated in pediatric neurosurgery. Currently, more than 60% of congenital hydrocephalus cases are diag- nosed prenatally as fetal ventriculomegaly, because of advances in prenatal imaging techniques. In fetal hydro- cephalus cases, the prognosis of isolated ventriculomeg- aly varies widely, because it is indicative of multiple dis- eases. Therefore, effective tools for accurately predicting the functional outcome are required. On the other hand, recent advances in molecular bi- ology have made great contributions toward establishing a molecular diagnosis for some hereditary diseases. In congenital hydrocephalus, the genetic understanding of J Neurosurg Pediatrics 8:411–416, 2011 Prenatal molecular diagnosis of a severe type of L1 syndrome (X-linked hydrocephalus) Clinical article MaMi Y aMasaki, M.D., Ph.D., 1,2 Masahiro NoNaka, M.D., Ph.D., 2 Nobuhiro suzuMori, M.D., Ph.D., 3 hiroaki NakaMura, M.D., Ph.D., 4 hiroshi Fujita, M.D., 5 akira NaMba, M.D., Ph.D., 6 Y oshiMasa kaMei, M.D., Ph.D., 7 takahiro Y aMaDa, M.D., Ph.D., 8 ritsuko k. Pooh, M.D., Ph.D., 9 MitsuYo taNeMura, M.D., Ph.D., 10 Norihito suDo, M.D., 11 Masato Nagasaka, M.D., Ph.D., 12 eMa Y oshioka, 1 toMoko shoFuDa, M.s., 1 aND Y oNehiro kaNeMura, M.D., Ph.D. 1,2 1 Institute for Clinical Research; 2 Department of Neurosurgery, Osaka National Hospital, National Hospital Organization; 4 Department of Obstetrics and Gynecology, Osaka City Sumiyoshi Hospital; and 9 Clinical Research Institute of Fetal Medicine and Perinatal Medicine Clinic, Osaka; 3 Division of Molecular and Clinical Genetics, Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medicine, Nagoya; 5 Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki; 6 Department of Obstetrics and Gynecology, Saitama Medical University, Saitama; 7 Department of Obstetrics and Gynecology, Tokyo University Graduate School of Medicine, Tokyo; 8 Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo; 10 Tanemura Women’s Clinic, Nagoya; 11 Department of Obstetrics and Gynecology, Nagaoka Nish Hospital, Nagaoka; and 12 Department of Neurosurgery, Aichi Children’s Health and Medical Center, Obu, Japan Object. The aim of this study was to evaluate the feasibility of prenatal L1CAM gene testing for X-linked hy- drocephalus (XLH). Methods. In a nationwide study conducted in Japan between 1999 and 2009, the authors identifed 51 different L1CAM gene mutations in 56 families with XLH. Of these 56 families, 9 obligate carriers requested prenatal gene mutation analysis for the fetal L1CAM gene in 14 pregnancies. Results. In 2004, new clinical guidelines for genetic testing were established by 10 Japanese genetic medicine– related societies. These guidelines stated that the genetic testing of carriers should be done only with their consent and with genetic counseling. Therefore, because females are carriers, since 2004, L1CAM gene analysis has not been performed for female fetuses. The authors report on 7 fetal genetic analyses that were performed at the request of families carrying L1CAM mutations, involving 3 female (prior to 2004) and 4 male fetuses. Of the 7 fetuses, 3 (1 male and 2 female) carried L1CAM mutations. Of these 3, 1 pregnancy (the male fetus) was terminated; in the other cases, the pregnancies continued, and 3 female and 3 male babies without the XLH phenotype were born. Conclusions. Prenatal L1CAM gene testing combined with genetic counseling was benefcial for families carry- ing L1CAM mutations. (DOI: 10.3171/2011.7.PEDS10531) keY WorDs • X-linked hydrocephalus • L1CAM gene • prenatal diagnosis • amniotic fuid aspiration • chorionic villous sampling 411 Abbreviations used in this paper: AC = amniocentesis; CVS = chorionic villous sampling; PCR = polymerase chain reaction; XLH = X-linked hydrocephalus.