Comparación de las características epidemiológicas de los defectos del tubo neural clasificados según el fallo de los distintos puntos de cierre

Sanchís Calvo, A.; Martínez-Frías, M.aL.

doi:10.1016/S1695-4033(02)77965-4

Información del artículo

Objetivos

Estudiar las características epidemiológicas de los defectos del tubo neural (DTN) clasificados según la teoría del cierre múltiple del mismo e intentar relacionar distintos factores con el fallo de los distintos puntos de cierre.

Material y métodos

Se han utilizado los datos del Estudio Colaborativo Español de Malformaciones Congénitas (ECEMC) relativos al período de abril de 1976 y abril de 1995. Durante este período se diagnosticaron 757 DTN de origen no sindrómico que se clasificaron en grupos de DTN según el fallo de los distintos puntos de cierre y analizado una serie de variables comparando los distintos grupos de DTN entre sí.

Resultados y conclusiones

El 2,11 % de los DTN no sindrómicos recurren en los hermanos, pero la verdadera tasa de recurrencia en nuestro medio es más elevada, de 2,63 %, y es la que corresponde a las recurrencias observadas antes del año 1986, ya que a partir de entonces puede estar modificada por la posibilidad legal de aborto tras diagnóstico prenatal.

Los DTN clasificados según el fallo de los distintos puntos de cierre difieren entre sí en cuanto al peso y la mortalidad y en cuanto a su relación con el uso materno de ácido valproico y con la diabetes mellitus materna. Mientras el ácido valproico es más específico del fallo del cierre 1 y de la zona 1 1 5, la diabetes afecta preferentemente al cierre 4. Este punto de cierre 4 tiene condicionantes claramente genéticos; está afectado en síndromes génicos y los DTN por fallo de este cierre tienen predominio femenino, mayor número de abortos maternos y mayor recurrencia. Con frecuencia se presentan como polimalformados y tienen más malformaciones en familiares.

Palabras clave:

Defectos del tubo neural

Epidemiología del fallo de los distintos puntos de cierre del tubo neural

Objectives

To study the epidemiological characteristics of neural tube defects (NTD) classified according to the theory of multi-site closure of the neural tube and to correlate several factors with the failure of different closure sites.

Material and methods

We used the data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), collected from April 1976 to April 1995. During this time, 757 NTD of non-syndromic origin were diagnosed. These were classified into groups according to the failure of the point of closure and a range of variables were analyzed by comparing the different groups of NTD with each other.

Results and conclusions

Among non-syndromic NTD, 2.11 % recurred in siblings. However, the real recurrence rate in our population is 2.63 %, which corresponds with the recurrence rate observed before 1986. From this year the recurrence rate was modified by the legal possibility of abortion after prenatal diagnosis.

The infants with NTD classified according to multi-site closure failure of neural tube differed in weight, mortality, maternal use of valproic acid, and maternal diabetes mellitus. While valproic acid is more specific to failure of closure sites 1 and 1 + 5, maternal diabetes mellitus preferentially affects failure of closure site 4. Closure site 4 is clearly genetically determined: it is frequently observed in genetic syndromes, predominantly affects females and is associated with a higher rate of maternal abortions and higher recurrence. Moreover, it is frequently observed in infants with multiple congenital anomalies and is associated with a higher rate of malformations among relatives.

Key words:

Neural tube defects

Epidemiology of the multi-site closure failure of the neural tube

El Texto completo está disponible en PDF

Bibliografía

[1.]

J.A. Golden, G.F. Chernoff.

Anterior neural tube closure in the mouse: Fuel for disagreement with the classical theory.

Clinical Research, 31 (1983), pp. 127A

[2.]

M.I. Van Allen, D.K. Kalousek, G.F. Chernoff, D. Juriloff, M. Harris, B.C. McGillivray.

Evidence for multi-site closure of the neural tube in humans.

Am J Med Genet, 47 (1993), pp. 723-743

http://dx.doi.org/10.1002/ajmg.1320470528 | Medline

[3.]

A. Sanchís Calvo, M.L. Martínez-Frías.

Estudio clínico epidemiológico de los defectos del tubo neural clasificados por los cincos puntos del mismo.

An Esp Pediatr, 54 (2001), pp. 165-173

Medline

[4.]

D.M. Juriloff, M.J. Harris.

Mouse models for neural tube closure defects.

Human Mol Gen, 9 (2000), pp. 993-1000

[5.]

T. Nakatsu, C.H. Uwabe, K. Shiota.

Neural tube closure in humans initiates at multiple sites: Evidence from human embryos and implications for the pathogenesis of neural tube defects.

Anat Embryol, 201 (2000), pp. 455-466

Medline

[6.]

M.L. Martinez-Frias, M. Urioste, E. Bermejo, A. Sanchis, E. Rodriguez Pinilla.

Epidemiological analysis of multi-site closure failure of neural tube in himans.

Am J Med Genet, 66 (1996), pp. 64-68

http://dx.doi.org/10.1002/(SICI)1096-8628(19961202)66:1<64::AID-AJMG14>3.0.CO;2-O | Medline

[7.]

M.L. Martinez-Frias, A. Sanchis, P. Aparicio, M. Blanco, M.J. Garcia, J. Gomez-Ullate.

Description of the characteristic of cases with non contiguous neural tube defects identified in a series of consecutive births.

Teratology, 57 (1998), pp. 13-16

http://dx.doi.org/10.1002/(SICI)1096-9926(199801)57:1<13::AID-TERA3>3.0.CO;2-8 | Medline

[8.]

M.L. Martínez Frías.

ECEMC, (1995),

[9.]

Catálogo de Especialidades Farmacéuticas 1997. Edita Consejo General de Colegios Oficiales de Farmacéuticos. ISBN: 84-87276-30-X

[10.]

J.G. Hall, J.M. Friedman, B.A. Kenna, J. Popkin, M. Jawanda, W. Arnold.

Clinical, genetic and epidemiological factors in neural tube defects.

Am J Hum Genet, 43 (1988), pp. 827-837

Medline

[11.]

G.M. Shaw, N.G. Jensvold, C.R. Wasserman, E.J. Lammer.

Epidemiologic characteristics of phenotipically distinct neural tube defcts among 0.7 million California births, 1983-1987.

Teratology, 49 (1994), pp. 143-149

http://dx.doi.org/10.1002/tera.1420490210 | Medline

[12.]

J.M. Elwood, J. Little, J.H. Elwood.

Epidemiology and control of neural tube defects.

Oxford: Oxford University Press, 306 (1994), pp. 23

[13.]

MRC (Medical Research Council) Vitamin study research group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin study.

Lancet, 338 (1991), pp. 131-137

Medline

[14.]

A.E. Czeizel, I. Dudas.

Prevention of the first ocurrence of neural tube defects by periconceptional vitamine supplementation.

N Engl J Med, 327 (1992), pp. 1832-1835

http://dx.doi.org/10.1056/NEJM199212243272602 | Medline

[15.]

C.Y. Ou, R.E. Stevenson, V.K. Bronw, C.E. Schwartz, W.P. Allen, M.J. Khoury.

5,10-methylenetetrahidrofolate reductase genetic polimorphisme as a risk factor for neural tube defects.

Am J Med Genet, 63 (1996), pp. 610-614

http://dx.doi.org/10.1002/(SICI)1096-8628(19960628)63:4<610::AID-AJMG15>3.0.CO;2-L | Medline

[16.]

K.A. Volcik, S.H. Blanton, G.H. Tyerman, S.T. Jong, T.Z. Page, N.K. Romaine.

Methylenetetrahydrofolate reductase and spina bifida.

Evaluation of level of defect and maternal genotypic risk in Hispanics, 95 (2000), pp. 21-27

[17.]

M.C. Koch, K. Stegmann, A. Ziegler, B. Schröter, A. Ermet.

Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population.

Eur J Pediatr, 157 (1998), pp. 487-492

Medline

[18.]

R. De Franchis, A. Buonincnti, C. Mandato, A. Pepe, M.P. Sperandeo, R. Del Gado.

The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy.

J Med Genet, 35 (1998), pp. 100-113

[19.]

R.J. Berry, M.P. Zhu Li, J.D. Erickson, D.D.S. Song Li, C.A. Moore, Hong Wang.

Prevention of neural tube defects with folic acid in China.

N Engl J Med, 341 (1999), pp. 1485-1490

http://dx.doi.org/10.1056/NEJM199911113412001 | Medline

[20.]

R. O'Rahilly, F. Müller.

Bidirectional closure of the rostral neuropore in the human embryo.

Am J Anat, 184 (1989), pp. 259-268

http://dx.doi.org/10.1002/aja.1001840402 | Medline

[21.]

M.L. Martínez Frías, L. Prieto, E. Bermejo, F. Gaya.

Estudio del peso al nacimiento sobre una población de niños sin defectos congénitos I. Curvas de percentiles de peso por edad gestacional.

An Esp Pediatr, 33 (1990), pp. 12-15

Medline

[22.]

Umbral'94. Estudio epidemiológico nacional sobre las patologías neonatales. AEP 1994

[23.]

H.V.F. Jordaan.

Newborn brain: Body weigth ratios.

Am J Phys Anthropol, 44 (1976), pp. 279-284

http://dx.doi.org/10.1002/ajpa.1330440210 | Medline

[24.]

M.I. Martinez Frias, J.A. Parralo, J. Salvador, J.L. Frías.

Sex ratios in neural tube defects.

Lancet, (1986), pp. 871-872

Medline

[25.]

M.J. Seller.

Neural tube defects and sex ratios.

Am J Med Genet, 26 (1987), pp. 699-707

http://dx.doi.org/10.1002/ajmg.1320260325 | Medline

[26.]

E.C. Mariman, B.C. Hamel.

Sex ratios of affected and transmitting members of multiple case families with neural tube defects.

J Med Genet, 29 (1992), pp. 695-698

Medline

[27.]

M.I. Van Allen.

Multisite neural tube closure in humans.

Birth Defects, 30 (1996), pp. 203-225

Medline

[28.]

M.J. Seller.

Sex, neural tube defects and multisite closure of the human neural tube.

Am J Med Genet, 58 (1995), pp. 332-336

http://dx.doi.org/10.1002/ajmg.1320580406 | Medline

[29.]

R.J. Costra, B. Baljet, R.C. Hennekan.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlans. IV: Closure defects of the neural tube.

Am J Med Genet, 80 (1998), pp. 60-73

Medline

[30.]

M.J. Khoury, J.D. Erickson, L.M. James.

Etiologic heterogeneity of neural tube defects: Clues from epidemiology.

Am J Epidemiol, 115 (1982), pp. 538-548

Medline

[31.]

M.L. Martínez Frías, J.L. Frías.

Are blastogenetic anomalies sporadicα.

Am J Med Genet, 68 (1997), pp. 381-387

Medline

[32.]

J. Byrne, A. Cama, M. Vigliarolo, L. Levato.

Patterns of inheritance in Irish and Italien families with neural tube defects: Comparison between high and low rate areas.

Ir Med J, 90 (1997), pp. 32-34

Medline

[33.]

A.G.W. Hunter, R.H. Cleveland, J.G. Blickman, L.B. Holmes.

A study of level, associated malformations and sib ocurrence risks in spine bifida.

Teratology, 54 (1996), pp. 213-218

http://dx.doi.org/10.1002/(SICI)1096-9926(199611)54:5<213::AID-TERA1>3.0.CO;2-0 | Medline

[34.]

B.M. Blatter, A.B. Lafebre, P.W. Peters, N. Roeleved, A.L. Verbeek, F.J. Gabreels.

Heterogeneity of spina bifida.

Teratology, 55 (1997), pp. 224-230

http://dx.doi.org/10.1002/(SICI)1096-9926(199704)55:4<224::AID-TERA2>3.0.CO;2-0 | Medline

[35.]

C. Papp, Z. Adam, E. Thót-Pál, O. Török, V. Varadi, Z. Papp.

Risk of recurrence of craniospinal anomalies.

J Matern Fetal Med, 6 (1997), pp. 53-57

http://dx.doi.org/10.1002/(SICI)1520-6661(199701/02)6:1<53::AID-MFM11>3.0.CO;2-N | Medline

[36.]

J. Little.

Risks in siblings and other relatives.

Epidemiology and control neural tube defects, pp. 456-520

[37.]

Y. Wang, Y. Wu, G. Zhou, C. Xu, K. Xiao.

An estimate of recurrence risk for neural tube defects in China.

Hua Hsi Y Ko Ta Hsueh Hsueh Pao, 27 (1996), pp. 196-198

[38.]

M.L. Martinez Frias.

Epidemilogical analysis of outcomes of pregnancy in the diabetics mothers: Identification of the most characteristic and most frequent congenital anomalies.

Am J Med Genet, 51 (1994), pp. 108-113

http://dx.doi.org/10.1002/ajmg.1320510206 | Medline

Indexada en:

Síguenos:

Indexada en:

Síguenos:

Suscríbase a la newsletter