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

Clinical article

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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.

Abbreviations used in this paper: AC = amniocentesis; CVS = chorionic villous sampling; PCR = polymerase chain reaction; XLH = X-linked hydrocephalus.

Article Information

Address correspondence to: Mami Yamasaki, M.D., Ph.D., Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, 2-1-14 Hoenzaka, Chuo-ku, Osaka City, 540-0006, Japan. email: yamasaki@onh.go.jp.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Flow chart showing the protocol for prenatal L1CAM mutation analysis used at Osaka National Hospital.

  • View in gallery

    A: Pedigree of family HC27. B: Postnatal CT scan of the patient (III-1) showing bilateral severe ventricular dilation. C: Result of L1CAM gene analysis showing the position of the G to C transition in intron 14. This L1CAM mutation was reported previously by Kanemura et al. in 2005.

  • View in gallery

    A: Pedigree of family HC45. B: Fetal MR imaging of fetus (II-3) at 20 weeks of gestation showing bilateral severe ventricular dilation. C: Result of L1CAM gene analysis showing the deletion of ACC, which is a novel L1CAM mutation. fd = fetal death due to twisting of the umbilical cord; GW = gestational weeks; sa = spontaneous abortion; TOP = termination of pregnancy.

  • View in gallery

    Case summary of HC53. Left: Pedigree of family HC53. Right: Result of L1CAM gene analysis showing the C to A transition, which is a novel L1CAM mutation.

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