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J L Frías

Publications and source records attributed to J L Frías.

At least 19 recordsLinked to original sources
PubMed2000

Pathogenetic classification of a series of 27,145 consecutive infants with congenital defects.

We studied a series of 27,145 consecutive infants with congenital defects and classified them into the currently recognized pathogenetic types of errors of morphogenesis, as defined by the International Working Group [Spranger et al., 1982: J Pediatrics 1:160-165]. Of all infants with congenital defects, 97.94% had malformations, 3.92% deformations, and 1.65% disruptions. Malformations associated with deformations were present in 3.12% of children with congenital anomalies, malformations with disruptions in 0.18%, deformations with disruptions in 0.07%, and malformations with deformations and disruptions in 0.14%. While deformations, including deformation sequences, were 2.38 times more common than disruptions and disruption sequences, isolated disruptions (1.27%) were more frequent than isolated deformations (0.59%). Knowledge of the frequencies of the different types of errors of morphogenesis (malformations, deformations, disruptions, developmental field defects, associations, complexes, unrecognized patterns of multiple congenital anomaly, and syndromes) may be of great value in the evaluation of patients with congenital anomalies.

Congenital Abnormalities↗
PubMed1999

Analysis of deformations in 26,810 consecutive infants with congenital defects.

Here we present the analysis of deformations observed in a series of 26,810 consecutive infants with congenital defects. We observed that 3.88% of these infants had deformations, for a prevalence figure of 0.07% live-born infants. From the present study we can conclude that there are three different types of deformation sequences: one with polyhydramnios, thin skin without dermal ridges, hypotonia, and multiple deformations (hypokinesia sequence), which is most often due to intrinsic problems; another with oligohydramnios, redundant thick skin, and multiple deformations, which can be produced by intrinsic or extrinsic factors; and the third, with normal amniotic fluid volume, which is due to compression of different causes. Deformations of extrinsic cause are more frequently isolated defects and have a better prognosis, while deformations of intrinsic origin are more frequently associated with other congenital anomalies and, generally, have a poor prognosis.

Congenital Abnormalities↗
PubMed1999

VACTERL as primary, polytopic developmental field defects.

Previously we proposed that the VACTERL association represents a dysmorphogenetic response of the primary developmental field, i.e., polytopic developmental field defects (DFD). As such, it should conform to the essential attributes of a DFD, namely, heterogeneity, homology, and phylogeneity. To study its heterogeneity, we analyzed the data of the Spanish Collaborative Study of Congenital Malformations (ECEMC). Our results confirm the observations indicating that the different patterns of defects that constitute this entity are not only clinically variable but also causally heterogeneous. This causal heterogeneity, which is of crucial importance in defining developmental fields, gives additional credence to the hypothesis that VACTERL constitutes a primary polytopic DFD.

Abnormalities, Multiple↗
PubMed1998

Epidemiological analysis of outcomes of pregnancy in gestational diabetic mothers.

The association between maternal diabetes mellitus and congenital defects has been well documented. However, few data exist on the potential teratogenic effect of gestational diabetes (GD). We analyzed 19,577 consecutive infants with malformations of unknown cause and compared the offspring of mothers with GD with those of nondiabetic mothers. The children with each of 20 types of selected anomalies among the two groups were used to calculate the odds ratio (OR). Because we used as a reference group for each congenital defect the rest of malformed infants, the value of the OR gives us the specificity between the association of GD and each congenital defect. Our analysis strongly supports the suggestion that GD is a significant risk for holoprosencephaly, upper/lower spine/rib, and renal and urinary system anomalies. GD is a heterogeneous disorder, which includes previously unrecognized and newly diagnosed nongestational diabetes mellitus (DM). Thus, it is possible that the teratogenic effect is related to latent DM. However, because it is not possible at this time to differentiate between these situations, pregnancies complicated by GD should be considered at risk for congenital anomalies. Prenatal ultrasound examination should be aimed particularly at the detection of abnormalities of the central nervous system, the renal and urinary system, and the spine/rib developmental field.

Diabetes, Gestational↗
PubMed1998

Errors of morphogenesis and developmental field theory.

Field theory provides a rational basis for birth defects terminology. During blastogenesis in higher metazoa, pattern formation in the primary field leads to the establishment of upstream expression domains of growth and transcription factors, which, in various permutations and at specific sites and times, lay down the pattern of progenitor fields. Further spatially coordinated, temporally synchronized, and epimorphically hierarchical morphogenetic events, mostly during organogenesis, lead to the attainment of final form in the secondary, epimorphic fields. Because of shared molecular determinants, spatial contiguity, and close timing of morphogenetic events during blastogenesis, most malformations arising during blastogenesis are polytopic, i.e., involving two or more progenitor fields, e.g., acrorenal, cardiomelic, gastromelic, or splenomelic anomalies. Defects of organogenesis tend to be monotopic malformations, e.g., cleft palate or postaxial polydactyly. We suggest that what were called "associations" (e.g., VATER, schisis) be designated primary polytopic developmental field defects, or simply polytopic field defects, and that the term "association" be reserved for the original definition of a statistical combination of anomalies (mostly of organogenesis) [Spranger et al. (1982): J Pediatr 100:160-165]. If genetically caused or predisposed, all structures involved in a polytopic or monotopic malformation are genetically abnormal, whereas the parts secondarily affected as a consequence of a malformation sequence (e.g., spina bifida) are genetically normal. Polytopic field anomalies, per se, must be distinguished from pleiotropy, although such anomalies may constitute a part of pleiotropy (e.g., in trisomy 18). Because they are downstream from pattern-forming events in the primary field, multiple anomalies of organogenesis more likely represent syndromal pleiotropy.

Congenital Abnormalities↗
PubMed1998

Congenital anomalies in the offspring of mothers with a bicornuate uterus.

BACKGROUND: Most of the reports on mothers with bicornuate uterus analyze fertility, reproductive capacity, and pregnancy outcomes. Very few of them, however, mention the risk for congenital anomalies in their offspring. Further, to our knowledge, no epidemiologic studies estimating the risk for congenital defects and analyzing the type of anomalies observed in infants born to mothers with bicornuate uterus have been reported. METHODS: Using a case-control study series, we estimated the risk of congenital anomalies in the offspring of women with a bicornuate uterus. To identify the specific defects associated with the presence of a bicornuate uterus in the mother, we analyzed 26 945 consecutive malformed infants from the Spanish Collaborative Study of Congenital Malformations and assessed the frequency of congenital anomalies in the offspring of mothers with a bicornuate uterus and in those born to mothers with a normal uterus. We then calculated the relative frequency, which is the quotient of the frequency of the individual defects in each group. This figure expresses the times each congenital defect is more frequent in infants of mothers with a bicornuate uterus than in those born to mothers with a normal uterus. RESULTS: Offspring of mothers with a bicornuate uterus had a risk for congenital defects four times higher than infants born to women with a normal uterus. The risk was statistically significant for some specific defects such as nasal hypoplasia, omphalocele, limb deficiencies, teratomas, and acardia-anencephaly. CONCLUSIONS: Offspring of mothers with bicornuate uterus are not only at high risk for deformations and disruptions, but also for some type of malformations.

Case-Control Studies↗
PubMed1998

[Epidemiological aspects of children of women with bicornuate uterus].

BACKGROUND: Most published papers on women with a bicornuate uterus analyze their fertility problems, as well as certain pregnancy complications. We have not found any epidemiological study on the infants of mothers with this uterine malformation. Only in some papers a reference is made about the relationship of maternal bicornuate uterus with congenital deformations and disruptions in their infants. PATIENTS AND METHODS: Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), which has a case-control methodology, some characteristics in a series of 26,945 malformed infants, such as birth weight, sex, gestational age, umbilical cord length, placental weight and maternal age, were analyzed by separating infants of mothers with normal uterus and those of mothers with a bicornuate uterus. RESULTS: Results showed that women with a bicornuate uterus have more daughters than sons and an increased risk for intrauterine growth retardation and prematurity with respect to infants of mothers with a normal uterus. On the other hand, the risk of having an infant with congenital defects is higher for women with a bicornuate uterus than for those with a normal uterus. CONCLUSIONS: Pregnancies of women with a bicornuate uterus have to be considered at risk since they have more risk for complications and for having an infant with congenital defects, premature birth and with intrauterine growth retardation.

Case-Control Studies↗
PubMed1997

Primary developmental field. III: Clinical and epidemiological study of blastogenetic anomalies and their relationship to different MCA patterns.

Opitz [1993: BD:OAS XXIX (1):3-37] suggested that during blastogenesis the entire embryo constitutes a developmental field, i.e., the primary developmental field. Based on this principle, he postulated that a single "hit," that during late morphogenesis would cause a monotopic malformation, during blastogenesis would produce a polytopic malformation or an association. Lubinsky [1986: Am J Med Genet [Supp1]2:6-16] had stated previously that "since the embryo develops in an integrated manner, organized and differentiating spatially, temporally, and in an epimorphically hierarchical manner, disturbances result in nonrandom patterns of anomalies." He then concluded that "associations are derivatives of causally nonspecific disruptive events acting on developmental fields." These concepts, confirmed by our epidemiological observations [Martínez-Frías, 1994: Am J Med Genet 49:45-51], imply that some associations are, by definition, abnormalities of blastogenesis that is, that their component congenital anomalies are produced by events occurring during the first 4 weeks of development. We present an analysis of the characteristics of blastogenetic anom-alies and their relationship with midline abnormalities, as well as with the schisis and VACTERL associations.

Blastocyst↗
PubMed1997

Epidemiological analysis of the schisis association in the Spanish registry of congenital malformations.

Since its description by Czeizel [1981: Am J Med Genet 10:25-35], there has been general acceptance of the schisis association as a distinct entity although, to the best of our knowledge, no other epidemiological study has confirmed its existence. Here we present an epidemiologic study on schisis defects and their associations with each other in children with and without blastogenetic defects. This study demonstrates that most cases represent the dysmorphogenetic response of the primary developmental field.

Blastocyst↗
PubMed1997

Are blastogenetic anomalies sporadic?

Opitz [Birth Defects, 1993, 1:3-37] postulated that sporadic defects of blastogenesis generally are highly lethal and have a low recurrence risk. We have observed that mothers of infants with blastogenetic defects have more previous abortions than mothers of children with nonblastogenetic defects or than mothers of control infants. Thus the high lethality of blastogenetic abnormalities may be responsible for the spontaneous abortions, and there may be a potential for an increased recurrence risk in some cases. Our results also show that the increased rate of spontaneous abortions is not similar for all blastogenetic defects, since it is not elevated in mothers of infants with neural tube defects (NTD). Further, our analysis does not confirm the relationship between spontaneous abortions in the preceding pregnancy and the occurrence of NTD previously reported by other authors.

Abnormalities, Multiple↗
PubMed1996

[Etiologic distribution of children with congenital defects].

INTRODUCTION: Although it has been generally admitted that we know the cause of congenital malformations in about 40% of the cases, these data are based on very few studies. PATIENTS AND METHODS: Here we present the distribution of 22,784 malformed infants in our country by type of cause of their defects. RESULTS: Our results show a great impact of chromosomal alterations in causing congenital anomalies. On the other hand, performing the chromosomal study will enable the diagnosis of genetic entities, as well as environmental ones that are clinically similar to the clinical patterns produced by chromosomal abnormalities. CONCLUSIONS: We can recognize the cause of congenital defects in a proportion higher than the 40% which is generally accepted. Nowadays, there is no reason that justifies not performing a chromosomal study with high resolution band techniques in infants with congenital defects.

Congenital Abnormalities↗
PubMed1995

Kabuki make-up (Niikawa-Kuroki) syndrome in five Spanish children.

We describe 5 Spanish children with Kabuki make-up syndrome (KMS)-3 females and 2 males-identified in Badajoz, Spain, between 1988 and 1990. All had the characteristic clinical and radiological manifestations of the syndrome. Psychomotor/mental retardation, postnatal growth deficiency, distinctive facial appearance, sagittal vertebral clefts, and dermatoglyphic abnormalities were present in all 5. Congenital heart defects were present in 4 patients. In addition, one had myopia, astigmatism, and bilateral paralysis of the VI cranial nerve. Another had apparent fusion of the hamate and capitate. An additional patient, as well as his mother, had an apparently balanced 15/17 translocation [46,XY,t(15;17) (15q;21q)]. The fact that these patients were ascertained in a catchment area of approximately 250,000 inhabitants and in a relatively limited period of time suggests that the prevalence of the KMS may be higher than previously recognized.

Abnormalities, Multiple↗
PubMed1993

Hypertrichosis, atrophic skin, ectropion, and macrostomia (Barber-Say syndrome): report of a new case.

We report on a child, born to a consanguineous parents, who presented with a multiple congenital anomalies (MCA) pattern consisting of severe hypertrichosis, macrostomia, ectropion, and atrophic skin. To our knowledge this is the third case with this combination of defects. The two previous cases were reported by Barber et al. [Syndrome Identification VIII(1):6-9, 1982], and David et al. [Am J Med Genet 41:192-195, 1991].

Abnormalities, Multiple↗
PubMed1993

Brain magnetic resonance imaging findings in the Opitz G/BBB syndrome: extension of the spectrum of midline brain anomalies.

We report the brain magnetic resonance imaging findings in 4 patients with the Opitz BBB/G syndrome. The scans were assessed by subjective interpretation and computerized image analysis. Findings noted in 3 of the 4 patients include hypoplasia or agenesis of the corpus callosum (3 patients), cerebellar vermal hypoplasia (2 patients), cortical atrophy and ventriculomegaly (3 patients), macro cisterna magna (3 patients), and a wide cavum septum pellucidum (1 patient). One patient had a normal scan. The demonstration of a wide cavum septum pellucidum extends the spectrum of midline brain anomalies (ventral induction defects) reported in this condition. This study along with other recent reports suggests that midline brain anomalies may be frequent findings in Opitz syndrome.

Adult↗
PubMed1992

Tracheoesophageal fistula, gastrointestinal abnormalities, hypospadias, and prenatal growth deficiency.

We studied 2 sibs, born to consanguineous parents, who presented with an MCA pattern which includes low birthweight, tracheoesophageal fistula, duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas, and hypospadias. This constellation of congenital anomalies appears to be a previously unreported autosomal recessive syndrome. A computerized search of the data files of the Spanish Collaborative Study of Congenital Malformations (ECEMC) identified 3 other unrelated infants with intestinal atresias, hypospadias, and low birth weight. These cases may represent a milder expression of the same syndrome.

Abnormalities, Multiple↗