Scheuerle A.E.,Tesserae Genetics
Archives of Pediatrics and Adolescent Medicine | Year: 2011
Objective: To examine factors that may explain a 9-fold increase in plagiocephaly in Texas from 1999 to 2007. Design: Descriptive epidemiologic study of time trends and a nested case-control study. Setting: Texas. Participants: Cases in the Texas Birth Defects Registry. Outcome Measures: Time trends in the birth prevalence of plagiocephaly overall and by region, demographic group, and clinical subgroup. Trends in percentage of cases using specific facilities or procedures. Results: From 1999 to 2007, the prevalence of plagiocephaly in Texas increased from 3.0 cases per 10 000 live births to 28.8, an average increase of 21.2% per year. This was highly statistically significant. The time trend was most pronounced in the Dallas/Fort Worth region and in certain health care facilities. It was observed in all demographic and clinical subgroups. Cases born in 2004 and 2005 were not more likely to be postnatally acquired when compared with cases born in 1999 and 2000. There was no commensurate decrease in other birth defects of the face or skull. Conclusions: A small part of the trend might have been due to delayed compliance with the infant supine sleeping recommendation and a slight increase in preterm births. It was not due to changes in birth defect coding practice or trends in multiple births, torticollis, or oligohydramnios. Because the plagiocephaly trend was observed mainly in patients visiting certain health care facilities, among mild cases, and among cases with minimally invasive procedures, we suspect it may be due mainly to changes in available therapies and insurance reimbursement practices. ©2011 American Medical Association. All rights reserved.
Colpitts L.R.,Tesserae Genetics
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2012
Objective.To describe the patterns of cesarean section (CS) and vaginal delivery by type of birth defect and determine whether prenatal diagnosis predicts a higher or lower likelihood of CS for selected defect categories. Methods.Data from a large population-based registry were analyzed to determine percentages of vaginal versus CS delivery for each of 49 categories of birth defects. Odds ratios and statistical significance were computed to determine if a record of prenatal diagnosis (PND) predicted delivery mode. Cases were liveborn children with any of these defects born in Texas between 1997 and 2005. Results.Forty-three percent of infants in the study were delivered by CS, with a range of 25.3% (aniridia) to 62.4% (spina bifida). A record of prenatal diagnosis of the primary assigned birth defect was found in 43.0% of all records but varied substantially by defect category. PND significantly predicted higher CS percentages for spina bifida without anencephaly, encephalocele, hydrocephaly, transposition of the great vessels, ventricular septal defect, pulmonary valve atresia/stenosis, craniosynostosis, diaphragmatic hernia, gastroschisis, and trisomy 21. Vaginal delivery was predicted by PND of anencephaly, agenesis, aplasia, or hypoplasia of the lung, renal agenesis or dysgenesis, and trisomy 18. Conclusion.Texas children with birth defects are more likely to have been delivered by CS than the population in general. For several types of defects, prenatal diagnosis is predictive of higher odds of CS; for others, especially fatal defects, PND predicts lower CS likelihood. © 2012 Informa UK, Ltd.
Simmons K.,University of Houston |
Hashmi S.S.,University of Houston |
Scheuerle A.,Tesserae Genetics |
Hecht J.T.,University of Houston
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2014
BACKGROUND: Natural history studies performed 30 years ago identifying higher mortality among children born with achondroplasia, a genetic dwarfing condition, resulted in clinical recommendations aimed at improving mortality in childhood. The objective of this study was to determine if mortality rates have changed over the past few decades. METHODS: Children born with achondroplasia during 1996 to 2003 were ascertained from the Texas Birth Defects Registry and matched with death certificate data from the Bureau of Vital Statistics through 2007. Infant and overall mortality rates, both crude and standardized to the 2005 (SMR2005) and 1975 (SMR1975) U.S. populations, were calculated. RESULTS: 106 children born with achondroplasia were identified. Four deaths were reported, with all occurring in the first year of life (mortality rate: 41.4 /1000 live-births). Infant mortality was higher when standardized to the 2005 U.S. population (SMR2005:6.02, 95% CI:1.64-15.42) than the 1975 population (SMR1975:2.58, 95% CI:0.70-6.61). CONCLUSION: The higher SMR2005 compared with SMR1975, along with the fact that SMR1975 was nearly half that of a previous cohort reported 25 years ago (rate ratio: 0.53, 95% CI: 0.11-2.25), reflect a discrepancy in the changes in mortality in the overall population and in our cohort. Although an overall improvement in mortality, especially after the first year of life, is observed in our cohort, children with achondroplasia are still at a much higher risk of death compared with the general population. A longer follow-up is needed to elucidate whether evaluation/intervention changes have resulted in significant improvement in long-term survival among these patients. © 2014 Wiley Periodicals, Inc.
Abiri O.O.,Texas A&M University |
Scheuerle A.E.,Tesserae Genetics
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2011
Background Few population-based studies exist on descriptive epidemiologic characteristics of rare heritable birth defects. The number of birth defect cases in the Texas Birth Defects Registry (one of the largest active birth defects surveillance systems in the world) enabled us to examine six different heritable disorders (aqueductal stenosis, infantile polycystic kidney disease, achondroplasia, thanatophoric dwarfism, chondrodysplasia/dwarfism not otherwise specified (NOS), and osteogenesis imperfecta) for a variety of descriptive demographic variables. Methods The Texas Birth Defects Registry was used to identify infants or fetuses with heritable birth defects. Crude prevalence rates were calculated and Poisson regression was used to test the association of each demographic variable (e.g., maternal age) with each of the selected genetic birth defects. Results White non-Hispanics exhibited higher rates of achondroplasia and osteogenesis imperfecta than other race/ethnic groups. Lower maternal education level and to a lesser extent, paternal education level, was associated with higher rates of several disorders. The birth prevalence rate for achondroplasia decreased from 1999 through 2006. Conclusion The use of a large birth defects registry provides a sufficient count of cases to perform some basic epidemiologic analysis on selected rare heritable birth defects. © 2011 Wiley Periodicals, Inc.
Scheuerle A.E.,Tesserae Genetics
American Journal of Medical Genetics, Part A | Year: 2014
Since 1983, several authors have used panels of "sentinel" congenital anomalies that might serve as indicators of the human genome mutation rate. The current study suggests a considerably updated panel, and applies it to public health birth defects registry data to determine the potential number of de novo cases. Data were taken from deliveries in 1999-2009 from the Texas Birth Defects Registry, an active surveillance program. Cases with one of the conditions or syndromes in the panel were identified using codes and text searches. Frequencies and birth prevalence were calculated for the overall panel and subcategories within it. Of the 60 conditions appearing in previous papers on sentinel phenotypes, 21 (35%) were used in the current study along with 27 new phenotypes. We found 1,694 cases. Of those, 1,100 exhibited phenotypes thought to arise de novo in at least 90% of the cases ("all/almost all" subpanel), and 594 considered de novo in roughly 50-90% of cases ("most" subpanel). Chromosomal deletion disorders were present in 523 cases and imprinting disorders in 243. After adjusting for maternal age, occurrence of cases in the total panel, "most" subpanel, and imprinting disorders subpanel were significantly associated with paternal age. Our panel of sentinel phenotypes differs from previous panels due to evolved knowledge of genetic disorders, different approaches with respect to interviewing, and different operational definitions. It is hoped that using an overall panel as well as subpanels may maximize statistical power as well as suggest potential mechanisms. © 2014 Wiley Periodicals, Inc.
Jandle L.,Laboratory Services Unit |
Scheuerle A.,Tesserae Genetics |
Horel S.A.,Texas A&M University |
Carozza S.E.,Oregon State University
Journal of Rural Health | Year: 2010
Purpose: (1) Determine if there is an association between 3 conotruncal heart birth defects and urban/rural residence of mother. (2) Compare results using different methods of measuring urban/rural status.Methods: Data were taken from the Texas Birth Defects Registry, 1999-2003. Poisson regression was used to compare crude and adjusted birth prevalence.Findings: Based on residences of births in Texas, the values for urban influence code (UIC), rural urban continuum code (RUCC), and rural urban commuting area (RUCA) were highly correlated with each other and, less highly, to percentage of land in crops. For tetralogy of Fallot, the most rural category consistently showed the highest prevalence ratio for all measures. The adjusted prevalence ratio for highest percentage cropland was 1.73 [95% CI, 1.14-2.51] using natural breaks and 1.42 [95% CI, 1.07-1.86] using quartiles. The trend with cropland percentage was significant (P < .03), whether crude or adjusted. The crude trend was also significant using RUCC. Neither truncus arteriosus nor transposition of the great arteries exhibited consistent associations with urban or rural residence.Conclusions: The urban/rural measures were generally correlated with each other; as a broad measure, RUCA has advantages for many health studies. Tetralogy of Fallot was most prevalent in rural areas; that pattern was strongest using percentage of land in crops. © 2010 National Rural Health Association.
Namazy J.,Scripps Research Institute |
Cabana M.D.,University of California at San Francisco |
Scheuerle A.E.,Tesserae Genetics |
Thorp J.M.,University of North Carolina at Chapel Hill |
And 5 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015
Background For many asthma medications, pregnancy safety data remains insufficient. Objective The omalizumab pregnancy registry, EXPECT, evaluates maternal, pregnancy, and infant outcomes after exposure to omalizumab, including incidence of congenital anomalies. Methods EXPECT is a prospective, observational study of pregnant women exposed to ≥1 dose of omalizumab within 8 weeks prior to conception or at any time during pregnancy. Primary outcome measures include rates of live births, elective terminations, stillbirths, and congenital anomalies. Data were collected at enrollment, each trimester, birth, and every 6 months up to 18 months post-delivery. Results As of November 2012, 188 of 191 pregnant women were exposed to omalizumab during their first trimester. Of 169 pregnancies with known outcomes (median exposure during pregnancy, 8.8 months), there were 156 live births of 160 infants (4 twin pairs), 1 fetal death/stillbirth, 11 spontaneous abortions, and 1 elective termination. Among 152 singleton infants, 22 (14.5%) were born prematurely. Of 147 singleton infants with weight data, 16 (10.9%) were small for gestational age. Among 125 singleton full-term infants, 4 (3.2%) had low birth weights. Overall, 20 infants had congenital anomalies confirmed, 7 (4.4%) of whom had 1 major defect. No pattern of anomalies was observed. Conclusions To date, proportions of major congenital anomalies, prematurity, low birth weight, and small size for gestational age observed in the EXPECT registry are not inconsistent with findings from other studies in this asthma population. Recognizing the small sample size available, no apparent increased birth prevalence of major anomalies or patterns of major anomalies has been observed. © 2014 American Academy of Allergy, Asthma & Immunology.
Coyle P.K.,Comprehensive Care |
Sinclair S.M.,University of North Carolina at Wilmington |
Scheuerle A.E.,Tesserae Genetics |
Thorp Jr. J.M.,University of North Carolina at Chapel Hill |
And 2 more authors.
BMJ Open | Year: 2014
Objective: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population. Design: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit. Setting: Patients in the USA who met these criteria were enrolled in the registry. Results: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit. Conclusions: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b. Clinical trials registration number: NCT00317564.
Conte M.I.,CNR Institute of Neuroscience |
Pescatore A.,CNR Institute of Neuroscience |
Paciolla M.,CNR Institute of Neuroscience |
Esposito E.,CNR Institute of Neuroscience |
And 19 more authors.
Human Mutation | Year: 2014
Incontinentia pigmenti (IP) is an X-linked-dominant Mendelian disorder caused by mutation in the IKBKG/NEMO gene, encoding for NEMO/IKKgamma, a regulatory protein of nuclear factor kappaB (NF-kB) signaling. In more than 80% of cases, IP is due to recurrent or nonrecurrent deletions causing loss-of-function (LoF) of NEMO/IKKgamma. We review how the local architecture of the IKBKG/NEMO locus with segmental duplication and a high frequency of repetitive elements favor de novo aberrant recombination through different mechanisms producing genomic microdeletion. We report here a new microindel (c.436_471delinsT, p.Val146X) arising through a DNA-replication-repair fork-stalling-and-template-switching and microhomology-mediated-end-joining mechanism in a sporadic IP case. The LoF mutations of IKBKG/NEMO leading to IP include small insertions/deletions (indel) causing frameshift and premature stop codons, which account for 10% of cases. We here present 21 point mutations previously unreported, which further extend the spectrum of pathologic variants: 14/21 predict LoF because of premature stop codon (6/14) or frameshift (8/14), whereas 7/21 predict a partial loss of NEMO/IKKgamma activity (two splicing and five missense). We review how the analysis of IP-associated IKBKG/NEMO hypomorphic mutants has contributed to the understanding of the pathophysiological mechanism of IP disease and has provided important information on affected NF-kB signaling. We built a locus-specific database listing all IKBKG/NEMO variants, accessible at http://IKBKG.lovd.nl. © 2013 WILEY PERIODICALS, INC.
Scheuerle A.,Tesserae Genetics |
Wilson K.,Southwestern University
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2011
Microdeletions of PARK2 have been reported previously in seven patients with autism spectrum disorder. There are no reports of PARK2 microduplications in this population. Presented are two patients, one with deletion and the other with duplication, both with autism spectrum disorder, though their syndromic phenotypes vary. The deletion patient is cognitively normal and ectomorphic: the duplication patient is cognitively impaired, underweight and short. Further, the microduplication patient has demonstrated adverse medication reactions to psychotropic medications active in the dopamine metabolic pathway: cyclopentolate, lisdexamfetamine, methylphenidate. These patients support an association between PARK2 mutations and autism spectrum disorder and suggest that duplications may be equally causative. It is hypothesized that the disparate patient phenotypes may represent a deletion/duplication syndrome and that the adverse medication reactions may be a pharmacogenetic phenomenon. © 2011 Wiley-Liss, Inc.