Prenatal molecular diagnosis of a severe type of L1 syndrome (X-linked hydrocephalus).

OBJECT The aim of this study was to evaluate the feasibility of prenatal L1CAM gene testing for X-linked hydrocephalus (XLH). METHODS In a nationwide study conducted in Japan between 1999 and 2009, the authors identified 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 beneficial for families carrying L1CAM mutations.