American Journal of Medical Genetics 39241 (1991)

Letter to the Editor

Are the Neurulation and Canalization Forms of Neural Tube Defects Causally Distinct?

To the Editor: TABLE 11. Level of Defect in (Three) Affected Individuals

Several investigations have been published on the pathogenesis and cause of neural tube defects (NTDs). However, still more data are needed for a better under- standing of this problem. From embryological consider- ations NTDs can be separated into two groups based on the level of the lesion: so-called neurulation (upper) and canalization (lower) defects. Two previous studies [Toriello and Higgins, 1985; Hall and Keena, 19861 sug- gested causal heterogeneity between these two groups, as 100% concordance for the type of the defect was found among affected sib pairs.

In contrast, Frecker et al. [1988] found 4 sib pairs of 11 to be discordant for the level of the lesion, suggesting that genetically the two groups are not distinct. This finding was recently supported by Seller [ 19901. In her study, 7 of 38 sibships were discordant; in her opinion further evidence for a common underlying factor is that both types occurred despite maternal periconceptional multivitamin supplementation.

At the Genetic Counseling Clinic of the Department of Obstetrics and Gynecology in the University Medical School of Debrecen, 1,044 families have been counseled for NTD. In 21 families there were two (in 2 families one of the parents and the fetus), and in 4 families three affected individuals (Tables I and 11). Only those fami- lies were included in our recent study that had had affected fetuses in the pregnancy subsequent to the first

TABLE I. Level of Defect in (Two) Affected Individuals Case no. _- Defect in first sib Defect in second sib _ _ _ _ _ ~ _ _ _ _ _ _ _ _ _

Anencephaly Craniorachischisis 1 Anencephaly Encephalocele 1 Craniorachischisis Anencephaly 1 Exencephaly Exencephaly 1 Encephalocele Encephalocele 2 Encephalocele Craniorachischisis 1 Spina bifida T-L Craniorachischisis 1 Spina bifida C-L Craniorachischisis 1 Spina bifida S a Spina bifida L-S 1 Spina bifida L-S Spina bifida L-S 3 Exencephaly Spina bifida L-S 1 Spina bifida La Spina bifida C-S 1 ^Closed defect of the mother.

Defect in Defect in Defect in first sib second sib third sib Anencephaly Anencephaly Craniorachischisis Anencephaly Exencephaly Anencephaly Anencephaly Exencephaly Craniorachischisis Encephalocele Encephalocele Anencephaly In the four families with three affected individuals (Table 11) 100% concordance was found among affected sib pairs. However, 2 families out of the 15 with two affected individuals (Table I) were discordant for the level of the lesion. Our findings serve as further evidence against the presumption that neurulation and canalization defects are genet- ically distinct.

attendance at the clinic. Those cases with multiple ab- normalities were excluded as well.

All 25 recurrences with the exception of 2 were diag- nosed prenatally and thorough fetopathological exam- ination was performed after termination. One encepha- locele and one small lumbosacral spina bifida were missed.

In 6 of 21 families the data from medical records or autopsy reports were not available for the determination of the level of the lesion in the index patient. The divid- ing line for classification into two groups, as in previous studies, was T l l IT 12.

REFERENCES Frecker MF, Fraser FC, Heneghan WD (1988): Are “upper”and “lower”

neural tube defects aetiologically different? J Med Genet 25: 503-504.

Hall JG, Keena FC (1986): Adjusting recurrence risks for neural tube defects based on B.C. data. Am J Hum Genet 39:A64.

Seller MJ (1990): Neural tube defects: Are neurulation and canaliza- tion forms causally distinct? Am J Med Genet 35:394-396.

Toriello HV, Higgins JV (1985): Possible causal heterogeneity in spina bifida cystica. Am J Med Genet 21:13-20.

0. Torok Z. Papp Department of Obstetrics and Gynecology University Medical School of Debrecen and I. Department of Obstetrics and Gynecology Semmelweis University Medical School Budapest, Hungary

Received for publication September 11, 1990.

0 1991 Wiley-Liss, Inc.