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Biomedical subjects

C J Curry

Publications and source records attributed to C J Curry.

At least 19 recordsLinked to original sources

Ritscher-Schinzel (3C) syndrome: documentation of the phenotype.

Ritscher-Schinzel syndrome or 3C (craniocerebello-cardiac) syndrome is characterized by cardiac defects, cerebellar vermis hypoplasia, and cranial defects. Nineteen cases were reported previously; however, the full spectrum of this disorder has not been determined. We have evaluated two unrelated males with this condition. Both had defects of the endocardial cushion and vermis hypoplasia with hypotonia. In addition, both had hypospadias, a previously undescribed finding of this disorders. Review of the previously reported cases and those described herein demonstrate: 1) Although varying degrees of vermis hypoplasia are accompanied by hypotonia, delayed gross motor function improves with advancing age leaving speech delay as the major neurodevelopmental handicap. 2) Two different types of cardiac anomalies occur: defects of the endocardial cushion ranging from anomalies of the mitral or tricuspid valves to complete AV canal, and/or conotruncal defects. 3) Postnatal growth deficiency was seen in most patients in whom longitudinal information was available. In our review of patients with vermis hypoplasia we ascertained a patient diagnosed as having "Joubert syndrome" who had most findings of the Ritscher-Schinzel syndrome and several other patients with "Dandy-Walker syndrome" who likely have had Ritscher-Schinzel syndrome, suggesting that Ritscher-Schinzel syndrome is more common than has been appreciated. Careful search for the subtle facial changes characteristic of this disorder as well as coloboma, cleft palate/bifid uvula, short neck, syndactyly, and hypoplasia of the nails is warranted when evaluating children with Dandy-Walker malformation with or without clinical signs of Joubert syndrome.

Abnormalities, Multiple

Maternal medications and environmental exposures as risk factors for gastroschisis.

In a case-control study of gastroschisis, we evaluated the risks associated with mother's first-trimester use of medications and with hobby or occupational exposures for 110 cases and 220 controls without a birth defect. Mothers of cases and controls were age-matched. For hobby or occupational exposures, we found significantly elevated risks for high levels of solvents (odds ratio (OR) = 3.8; 95% confidence interval (CI) = 1.6-9.2) and for colorants (OR = 2.3; 95% CI = 1.3-4.0). For medications, we found significantly elevated risks for two strong cyclooxygenase inhibitors, aspirin (OR = 4.7; 95% CI = 1.2-18.1) and ibuprofen (OR = 4.0; 95% CI = 1.0-16.0), but not for acetaminophen, a weak cyclooxygenase inhibitor. Periconceptional exposure to X rays was also associated with gastroschisis (OR = 2.5; 95% CI = 1.2-5.5), but exposure to antibiotics, antinauseants, sulfonamides, or oral contraceptives was not. We also found elevated risks for two decongestants, pseudoephedrine (OR = 2.1; 95% CI = 0.8-5.5) and phenylpropanolamine (OR = 10.0; 95% CI = 1.2-85.6). For the group of all decongestants, including also oxymetazoline and ephedrine, the risk was significantly elevated (OR = 2.4; 95% CI = 1.0-5.4). Controlling in multivariate analyses for several demographic and pregnancy variables associated with gastroschisis in a previous analysis [Torfs et al. (1994) Teratology 50: 44-53] did not substantially change the level or direction of the associations. Most of these associations are for vasoactive substances, which supports a vascular hypothesis for the pathogenesis of gastroschisis.

Abdominal Muscles

Population-based study of tracheoesophageal fistula and esophageal atresia.

From a multiracial population of 1,035,384 births monitored by the California Birth Defects Monitoring Program (CBDMP) from 1983 to 1988, we ascertained 34 cases of esophageal atresia (EA), 204 cases of tracheoesophageal fistula (TEF) with an EA (TEF/EA), and 54 cases of TEF without EA. The total prevalence rate was 2.82 per 10,000 live births and stillbirths and showed no secular trend nor marked seasonal variation. Rates of multiple birth were high for each defect (TEF 3.7%, TEF/EA 4.9%, EA 8.8%; population 1.1%). Non-Hispanic whites were overrepresented for TEF and TEF/EA, but not for EA. Excluding trisomies, mean maternal age was above the population mean (26.8 years) for TEF (27.9 years) and TEF/EA (28.0 years), but not for EA (26.2 years). The proportion of trisomies was significantly higher for EA (23.5%) than for TEF (9.3%; P < 0.02) or for TEF/EA (7.4%; P < 0.003). We subdivided each defect into five mutually exclusive types: isolated, multiple, syndromic, chromosomal, and trisomic. Male-to-female (M/F) ratios varied considerably between types, both within and between defects. The highest M/F ratios within each defect were for the multiple type (TEF 2.29, TEF/EA 1.44, EA 1.33; population 1.05), and the lowest for trisomies (TEF 0.25; TEF/EA 0.25, and EA 0.60). All types except trisomies were significantly associated with a single umbilical artery. We found an association of EA and TEF/EA with dextrocardia (3.1% of cases), and confirmed the association of primary hydrocephalus with TEF and TEF/EA (2.7% of cases). The proportion of cases with additional midline defects or VATER or VACTERL type anomalies was similar for all three defects, suggesting a common developmental pathogenesis. Epidemiologic differences between defects, and between types within defects, may reflect differences in timing of the pathological process or differences in susceptibilities (e.g., by sex or aneuploidy) and emphasize the need to evaluate each defect and its types separately in epidemiologic studies.

Adult

Neurofibromatosis-Noonan syndrome.

Type I neurofibromatosis (NF-1) and Noonan syndrome (NS) are two fairly common genetic disorders. Patients with features of both disorders have been described, but considerable variability of phenotypic expression occurs. As a result, the correct nosology of this syndrome is uncertain. We present a patient with full expression of both NF-1 and NS phenotypes, and discuss the debate regarding the genetics of the combined syndrome.

Adult

D-2-hydroxyglutaric aciduria.

Hydroxyglutaric aciduria is detected by gas chromatographic-mass spectrometric analysis, and the D and L forms are quantified by chemical ionization with deuterated internal standards. Patients have recently been described who accumulate the D form, and they appear to be quite different from those with the more common L form. Experience is reported with three patients and an animal model with D-2-hydroxyglutaric aciduria. The phenotype appears to include mental retardation, macrocephaly, hypotonia, seizures, and involuntary movements, although neurologic and systemic manifestations of the disorder varied considerably between individual patients, even within the same family.

Animals

A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors.

Gastroschisis, an abdominal wall defect, most often occurs in infants of young mothers. To identify risk factors for gastroschisis, we conducted a case-control study in the population surveyed by the California Birth Defects Monitoring Program (CBDMP). From structured questionnaire data, we compared sociodemographic, reproductive, and lifestyle factors for 110 mothers of infants with gastroschisis with those for 220 age-matched mothers of normal infants. Univariate matched-pair analysis showed significant associations of gastroschisis with mother's education, yearly family income, marital status, a history of mother's mother smoking, mother's father's absence from home during the mother's youth, more than one elective abortion, a short interval between menarche and first pregnancy, siblings from different fathers, and use of either a recreational drug (either cocaine, amphetamine, marijuana, or LSD), alcohol, or tobacco during the trimester preceding pregnancy. For cocaine, amphetamine, and marijuana, use of more than one drug showed a stronger association than single drug use. The association was stronger if both parents used drugs. Although many variables were correlated, odds ratios (OR) were significant (95% confidence intervals) in multivariate conditional logistic analysis for: yearly family income < $10,000 [OR = 4.34 (1.54, 12.22)] or $10,000-$49,999 [OR = 3.93 (1.43, 10.80)]; mother's mother's smoking status not known [OR = 3.99 (1.66, 9.56)]; mother's father's absence from home during her youth [OR = 3.11 (1.14, 8.46)]; and drug use by mother [OR = 2.21 (1.21, 4.03)], father [OR = 1.66 (1.02, 2.69)], or both [OR = 3.05 (1.48, 6.28)]. The best predictive model explained 32% of the deviance. Young, socially disadvantaged women with a history of substance use were at highest risk for a child with a gastroschisis.

Abdominal Muscles

Congenital diaphragmatic hernia in the Brachmann-de Lange syndrome.

We present 12 children with typical Brachmann-de Lange syndrome and congenital diaphragmatic hernia. Affected children were more likely to be of low birth weight and to have major upper limb malformations. Hernia repair was attempted in 4 of these children, and only one survived past 12 months. Newborn infants with congenital diaphragmatic hernia should be examined carefully for evidence of the Brachmann-de Lange syndrome because diagnosis of this condition may influence their clinical management and prognosis.

De Lange Syndrome

Possible association between the hernia of Morgagni and trisomy 21.

Of the 5 liveborn infants with the hernia of Morgagni recorded in the California Birth Defects Monitoring Program, 3 had trisomy 21. This significant association (P < 10(-6)) between the hernia of Morgagni and trisomy 21 may reflect defective dorsoventral migration of rhabdomyoblasts from the paraxial myotomes, caused by increased cellular adhesiveness in trisomy 21.

Cell Movement

Familial cases of gastroschisis in a population-based registry.

Only a few familial cases of gastroschisis have been reported. Consequently, the risk of a recurrence has been thought to be very small. In a population-based study of gastroschisis that included an extended pedigree of all probands, 6 (4.7%) out of 127 families had more than one affected relative. The relationships of the affected were: sib, half-sib (2), first cousin, second cousin once removed, and great uncle. Sib recurrence was 3.5%. Our results suggest that pregnancies occurring in a family with a history of gastroschisis may be at higher risk of recurrence than previously thought.

Abdominal Muscles

A population-based study of congenital diaphragmatic hernia.

From 1983 through 1987, in a California population of 718,208 births, 237 infants were born with a congenital diaphragmatic hernia (CDH), a birth prevalence of 3.30 per 10,000 total births (live births and stillbirths). We proposed that the various types of this defect, characterized by their different pathogeneses, would be reflected in differences in their descriptive epidemiologies. We evaluated various demographic, maternal, and infant characteristics for three major types of defects, the Morgagni hernia, the pars sternalis hernia, and the posterolateral hernia, categorizing the latter type into isolated defect (N = 129), multiple congenital anomalies including nonchromosomal syndromes (N = 86), trisomies (N = 10), and chromosomal anomalies other than trisomies (N = 2). For the posterolateral hernia, we present the distribution of associated anomalies (43%) and specifically of midline defects (19%). Although the number of cases for the Morgagni hernia (N = 5) and the pars sternalis hernia (N = 5) were small, comparisons with the posterolateral hernia suggested lower sex ratios, of borderline significance for the pars sternalis hernia (P < 0.09), and higher mean maternal ages for both groups. Within the posterolateral type, we found a significantly higher male to female ratio (M/F = 1.58) only for the isolated subgroup compared to the population (P < 0.03), and a borderline significant rural/urban difference in prevalences (2.12 vs. 1.45 per 10,000) (P < 0.06). Additionally, the distribution of monthly prevalence rates adjusted for gestational age suggested opposite seasonal trends between the isolated and the other posterolateral hernias; within this latter subgroup the difference between the highest monthly rate (1.68) and the lowest (0.96) was of borderline significance (P < 0.09). Our results suggest the need to consider the respective types and subgroups of CDH separately in epidemiologic studies.

Abnormalities, Multiple

Pregnancy loss, stillbirth, and neonatal death. A guide for the pediatrician.

The complete clinical evaluation of pregnancy loss, stillborn infants, and neonatal deaths can result in the anticipation of an accurate diagnosis in a high percentage of cases. Appropriate focused fetal studies may include a clinical examination, fetal karyotype, photographs, skeletal radiographs, fetal autopsy, examination of the placenta and cord, and occasionally cultures or DNA studies. Knowledge of specific causes of fetal death and their clinical presentation can greatly assist the pediatrician in choosing the most appropriate studies. Many of the disorders leading to fetal death carry significant genetic recurrence risks, making an accurate diagnosis even more crucial. As our understanding of the causes of pregnancy loss improves, so does our ability to provide families with accurate counseling regarding their reproductive options.

Abortion, Spontaneous

Fellowships and career development in dysmorphology and clinical genetics.

This article sets forth some guiding principles for the initiation of a productive and satisfying academic career as a clinical researcher in the areas of dysmorphology, teratology, and clinical genetics. It assumes that the fellow in dysmorphology and clinical genetics is genuinely committed to the pursuit of a career in this area, but these general principles are certainly relevant to other medical specialties. It is important for pediatricians to consider careers in this area because the need for dysmorphologists and clinical geneticists will continue to increase during the foreseeable future, and the current opportunities for such training are limited.

Career Mobility

Isolated oral cleft malformations: associations with maternal and infant characteristics in a California population.

Data on isolated oral cleft malformations from a birth defects registry covering a large population base were examined to describe potential associations with maternal and infant characteristics. Infants with cleft palate (CP) were analyzed separately from infants with cleft lip with or without cleft palate (CLP). The prevalence of isolated CLP per 1,000 births was 0.741, approximately twice the prevalence of isolated CP, which was 0.383. Male infants were more likely to be born with CLP (OR = 1.9) but less likely to be born with CP (OR = 0.56) than were females. Women 39 years or more of age were twice as likely as 25-29 year olds to have a child with either type of cleft. Black, nonhispanic infants had a lowered risk for CLP compared to white, nonhispanics (OR = 0.40). These risks were found to be independent of each other based on multivariate analyses. Associations with either type of cleft malformation were not observed for plurality, number of previous live births, and maternal birthplace.

Adult

Clinical and molecular diagnosis of Miller-Dieker syndrome.

We report results of clinical, cytogenetic, and molecular studies in 27 patients with Miller-Dieker syndrome (MDS) from 25 families. All had severe type I lissencephaly with grossly normal cerebellum and a distinctive facial appearance consisting of prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw. Several other abnormalities, especially growth deficiency, were frequent but not constant. Chromosome analysis showed deletion of band 17p13 in 14 of 25 MDS probands. RFLP and somatic cell hybrid studies using probes from the 17p13.3 region including pYNZ22 (D17S5), pYNH37 (D17S28), and p144-D6 (D17S34) detected deletions in 19 of 25 probands tested including seven in whom chromosome analysis was normal. When the cytogenetic and molecular data are combined, deletions were detected in 21 of 25 probands. Parental origin of de novo deletions was determined in 11 patients. Paternal origin occurred in seven and maternal origin in four. Our demonstration of cytogenetic or molecular deletions in 21 of 25 MDS probands proves that deletion of a "critical region" comprising two or more genetic loci within band 17p13.3 is the cause of the MDS phenotype. We suspect that the remaining patients have smaller deletions involving the proposed critical region which are not detected with currently available probes.

Brain

Central nervous system damage and other anomalies in surviving fetus following second trimester antenatal death of co-twin. Report of four cases and literature review.

Four cases of multiple gestation with second trimester death of one fetus and subsequent damage to a survivor are reported. Monochorionic placentation was documented in three of the cases. Central nervous system lesions occurred in all cases, and bowel injury was noted in two of the damaged fetuses. Although rare maternal clotting problems have been reported in similar situations, none was noted in any of these four cases. Prior reports have indicated that losses in the first half of gestation were of no consequence to the surviving fetuses. These four cases contradict this suggestion, and indicate that close sonographic observation of the survivors is important in any multiple gestation where on fetus has died.

Abnormalities, Multiple

Rothmund-Thomson syndrome associated with trisomy 8 mosaicism.

This report describes a boy with Rothmund-Thomson syndrome associated with trisomy 8 mosaicism. The patient presented with typical features of Rothmund-Thomson syndrome but some of the features often seen in trisomy 8 mosaics were also observed in him. The possibility that the two disorders might share a common pathogenesis is postulated.

Child

A protocol for the investigation of pregnancy loss.

A protocol for the evaluation of pregnancy loss should include a maternal history, dysmorphic examination of the fetus or abortus, photographs, autopsy, chromosome studies (in most cases), and radiographic or xeroradiographic studies. Selected cases with suspected ascending or transplacental infection may require microbiologic investigation. Increasing specialized laboratory techniques may help in the diagnosis of inborn errors of metabolism or storage disorders. Coordination of studies requires the interaction of OB/GYN, pathology, genetics, cytogenetics, and nursing in order to assure delivery of this clinical service. Knowledge of the causes of pregnancy loss and their typical time and mode of presentation can facilitate a focused evaluation, with a high chance of achieving an accurate diagnosis. The goal of all investigations is to provide families with recurrence risk data on which to base future childbearing decisions, as well as information on potential prenatal monitoring.

Clinical Protocols