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Background: Despite rising costs of health care, physician awareness of costs remains poor. Educational initiatives to remedy this have shown promise, with gamification specifically having success, but actual improvements in physician estimation capabilities have yet to be evaluated. Objectives: The objective of the study was to assess a gamified educational session for emergency medicine residents that improved their ability to estimate the costs of tests or services commonly performed in their department. Methods: Participants completed an anonymous presession survey consisting of demographic data, self-analysis on cost awareness, and a 10-item cost estimation list. This was followed by a 1-h interactive gamified education session utilizing rules from the television show The Price is Right. During this session, only three of the survey items had their cost directly discussed such that the remaining seven were able to be assessed solely on estimation improvement instead of short-term knowledge retention. Participants then completed the same survey to assess for improvement in cost awareness. Results: Sixteen residents at the PGY-2 or PGY-3 level completed the surveys and education session. All self-analysis questions showed significant improvement in the postsession survey. Eight out of the 10 items had significant differences in cost estimation. Conclusions: A gamified teaching session using The Price is Right rules can improve a resident's estimation capabilities, even on items not directly taught during the session.
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Congenital disorders of glycosylation (CDG) are a group of rare autosomal recessive genetic disorders caused by pathogenic variants in genes coding for N-glycosylated glycoproteins, which play a role in folding, degrading, and transport of glycoproteins in their pathway. ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12. Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities. In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing.
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Trastornos Congénitos de Glicosilación , Enfermedades Renales Poliquísticas , Femenino , Humanos , Embarazo , Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/patología , Secuenciación del Exoma , Glicosilación , Mutación , Fenotipo , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/patología , MortinatoRESUMEN
BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid disorder. Affected patients often remain undiagnosed until the age of 20-30 years, when they have already developed significant neurologic disease that may not be reversible. An elevated plasma cholestanol concentration has been accepted as a diagnostic criterion for CTX for decades. OBJECTIVE: Full biochemical characterization was performed for three genetically and clinically confirmed atypical CTX cases with normal plasma cholestanol levels. METHODS: Clinical assessment and genetic/biochemical testing for patients with CTX was performed by their physician providing routine standard of care. RESULTS: We report three new atypical CTX cases with large extensor tendon xanthomas but normal plasma cholestanol levels. All three cases had marked elevations of bile acid precursors and bile alcohols in plasma and urine that decreased on treatment with chenodeoxycholic acid. We also review eight published cases of atypical CTX with normal/near normal circulating cholestanol levels. CONCLUSION: The atypical biochemical presentation of these cases provides a diagnostic challenge for CTX, a disorder for which cholestanol has been believed to be a sensitive biomarker. These cases demonstrate measurements of plasma cholestanol alone are insufficient to exclude a diagnosis of CTX. The data presented is consistent with the concept that bile acid precursors and bile alcohols are sensitive biomarkers for atypical CTX with normal cholestanol, and that such testing is indicated, along with CYP27A1 gene analyses, in patients presenting with significant tendon and/or tuberous xanthomas and/or neurologic disease in early adulthood despite normal or near normal cholesterol and cholestanol levels.
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Ácidos y Sales Biliares , Colestanol , Xantomatosis Cerebrotendinosa , Humanos , Xantomatosis Cerebrotendinosa/genética , Xantomatosis Cerebrotendinosa/diagnóstico , Xantomatosis Cerebrotendinosa/sangre , Colestanol/sangre , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Masculino , Adulto , Femenino , Ácido Quenodesoxicólico/uso terapéutico , Adulto Joven , Colestanoles/sangreRESUMEN
Aero-terrestrial algae are ecologically and economically valuable bioresources contributing to carbon sequestration, sustenance of soil health, and fertility. Compared to aquatic algae, the literature on subaerial algae is minimal, including studies of distinctive habitats such as forest soils, agricultural fields, deserts, polar regions, specific subaerial zones, artificial structures, and tropical soils. The primary goal here was to identify the gaps and scope of research on such algae. Accordingly, the literature was analyzed per sub-themes, such as the "nature of current research data on terrestrial algae," "methodological approaches," "diversity," "environmental relationships," "ecological roles," and "economic significance." The review showed there is a high diversity of algae in soils, especially members belonging to the Cyanophyta (Cyanobacteria) and Chlorophyta. Algal distributions in terrestrial environments depend on the microhabitat conditions, and many species of soil algae are sensitive to specific soil conditions. The ecological significance of soil algae includes primary production, the release of biochemical stimulants and plant growth promoters into soils, nitrogen fixation, solubilization of minerals, and the enhancement and maintenance of soil fertility. Since aero-terrestrial habitats are generally stressed environments, algae of such environments can be rich in rare metabolites and natural products. For example, epilithic soil algae use wet adhesive molecules to fix them firmly on the substratum. Exploring the ecological roles and economic utility of soil and other subaerial algae could be helpful for the development of algae-based industries and for achieving sustainable soil management.
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Chlorophyta , Cianobacterias , Suelo/química , Plantas/microbiología , EcosistemaRESUMEN
BACKGROUND: Adults with PKU have difficulty maintaining plasma phenylalanine (Phe) in the range that is safe for neurologic function. Elevated plasma Phe is a risk factor for congenital anomalies and developmental delay in offspring resulting from pregnancies with poor Phe control in women with PKU. Enzyme supplementation with pegvaliase allows adults with PKU to eat an unrestricted diet and have plasma Phe levels in a safe range for pregnancy but pegvaliase has not been approved for use in pregnant females with PKU. We report the results of chart review of 14 living offspring of females affected with PKU who were responsive to pegvaliase and chose to remain on pegvaliase throughout their pregnancy. METHODS: Fourteen pregnancies (one triplet pregnancy) and their offspring were identified at eight PKU treatment centers and medical records from pregnancy and birth were submitted for this study. Institutional Review Board approval was obtained. Responses to a dataset were provided to a single center and analyzed. RESULTS: Six females and eight males were born without congenital anomalies and all offspring had normal growth parameters. While mothers had preexisting comorbidities, no additional comorbidities were reported in the offspring. Four of eleven infants (excluding triplet pregnancies) were delivered preterm (36%), a higher rate than the general population (12%). A single first trimester (eight weeks) miscarriage in a 40y was not counted in this cohort of 14 live born infants. CONCLUSION: This retrospective study suggests that pegvaliase is effective at maintaining safe maternal blood Phe levels during pregnancy without deleterious effects on mother or child. A tendency toward premature birth (4/11; 36%) is higher than expected.
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Aborto Espontáneo , Fenilanina Amoníaco-Liasa , Fenilcetonurias , Adulto , Embarazo , Masculino , Recién Nacido , Lactante , Niño , Humanos , Femenino , Nacimiento Vivo , Estudios Retrospectivos , Aborto Espontáneo/epidemiología , Madres , Fenilalanina , Proteínas RecombinantesRESUMEN
Arbuscular mycorrhizal fungi (AMF) are effective natural alternatives to assist plants in improving crop productivity and immunity against pests and diseases. However, a comprehensive idea of the variables under which they show optimum activity, especially concerning particular soil, climate, geography, and crop characteristics, has yet to be adequately standardized. Since paddy is the staple food for half of the world's population, such standardization is highly significant globally. Research concerning determinants affecting AMF functioning in rice is limited. However, the identified variables include external variables such as abiotic, biotic, and anthropogenic factors and internal variables such as plant and AMF characteristics. Among the abiotic factors, edaphic factors like soil pH, phosphorus availability, and soil moisture significantly affect AMF functioning in rice. In addition, anthropogenic influences such as land use patterns, flooding, and fertilizer regimes also affect AMF communities in rice agroecosystems. The principal objective of the review was to analyse the existing literature on AMF concerning such variables generally and to assess the specific research requirements on variables affecting AMF in rice. The ultimate goal is to identify research gaps for applying AMF as a natural alternative in the sustainable agriculture of paddy with optimum AMF symbiosis enhancing rice productivity.
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Micorrizas , Oryza , Raíces de Plantas/microbiología , Microbiología del Suelo , Hongos , Agricultura , Suelo , Oryza/microbiologíaRESUMEN
Pathogenic variants in TRAF7 are often de novo and features of individuals harboring these variants are characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features. We present a familial case in two African American patients with a novel, likely pathogenic c.1936G>A variant in TRAF7. Patient 1 is a 31-year-old female with a patent ductus arteriosus (PDA), intellectual disability, ptosis, and other dysmorphic features. She was identified to harbor this likely pathogenic variant in a mosaic (33.89%) state in leukocytes. Her son, Patient 2, is a 10-month-old male with a PDA, atrial septal defect, ptosis, developmental delay, history of feeding difficulties, congenital maxillary frenulum, and malrotation of the intestine. He has the same variant in a non-mosaic state. These cases demonstrate the variable expressivity observed with variants in TRAF7 within the same family and expand upon current understanding of mosaic TRAF7 variants. They also provide phenotypic data on genetic variation in individuals with African American ancestry, a population who has been underrepresented in the literature and may be less frequently referred to genetic specialists.
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Blefaroptosis , Conducto Arterioso Permeable , Defectos del Tabique Interatrial , Discapacidad Intelectual , Anomalías Musculoesqueléticas , Síndrome de Circulación Fetal Persistente , Adulto , Femenino , Humanos , Lactante , Masculino , Negro o Afroamericano/genética , Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis TumoralRESUMEN
Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes.
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Anomalías Múltiples , Labio Leporino , Fisura del Paladar , Anomalías Congénitas , Microtia Congénita , Lactante , Femenino , Embarazo , Humanos , Microtia Congénita/epidemiología , Microtia Congénita/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/epidemiología , Anomalías Múltiples/genética , Texas/epidemiología , Anomalías Congénitas/diagnóstico , Anomalías Congénitas/epidemiología , Anomalías Congénitas/genéticaRESUMEN
OBJECTIVES: Our program implemented East EMWars, a year-long, longitudinal game that added competition to our existing curricular content. We surveyed residents to investigate the impact of gamification in emergency medicine residency training. We hypothesized that residents would report higher levels of motivation, engagement, and challenge with gamification compared to traditional didactics. Furthermore, we hypothesized that residents would exhibit generally positive perceptions about gamification as a learning tool and that it would translate to improved performance on the annual in-training examination. METHODS: This was a single-center, prospective pre- and post-intervention survey study at a community-based emergency medicine residency program. Given the multiplicity of research questions and inherent nature of educational research, a mixed methods approach was utilized. We utilized nonparametric testing for quantitative data with paired responses pre- and post-intervention. We solicited comments on the post-intervention that were categorized under thematic approach and presented in complete and unedited form in the results. RESULTS: Eighteen (100%) of eligible residents in our program participated in both surveys. There were statistically significant increases in reported levels of motivation, engagement, and challenge with gamification compared to traditional didactic methods. Residents also reported overwhelmingly positive general perceptions about gamification and its broader generalizability and applicability. We did not reach statistical significance in determining if in-training exam scores were associated with our gamification initiative. CONCLUSIONS: This study was a first-of-its-kind look into a longitudinal game in an emergency medicine residency program. Although our results are encouraging, medical educators need further research to determine if this increase in motivation, engagement, and challenge will be associated with an increase in examination scores or, more importantly, healthcare outcomes. Theory-based, broader-scale, prospective studies are needed to further explore and help establish these associations and outcomes.
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PURPOSE: Examine if Historically Black Colleges and Universities (HBCUs) are more likely to be located in low food access area (LFA) census tracts compared to public non-HBCUs. DESIGN: ArcGIS Pro was utilized to capture food environments and census tract sociodemographic data. SETTING: The sample included 98 HBCUs and 777 public non-HBCUs within the United States. 28.9% of study census tracts were classified as LFA tracts. MEASURES: University data were gathered from the National Center for Education Statistics. Census tract-level LFA classification was informed by the United States Department of Agriculture's Food Access Research Atlas. Covariates included population density and neighborhood socioeconomic status of census tracts containing subject universities. ANALYSIS: Multilevel logistic regression was employed to examine the relationship between university type and LFA classification. RESULTS: A higher percentage of HBCUs (46.9%) than public non-HBCUs (26.6%) were located in LFAs. After adjusting for population density and neighborhood socioeconomic status, university type was significantly associated with food access classification (B=0.71;p=.0036). The odds of an HBCU being located in LFA tracts were 104% greater than for a public non-HBCU (OR=2.04;95% CI=1.26,3.29). CONCLUSION: Findings underscore the need for policy interventions tailored to HBCU students to promote food security, environmental justice, and public health.
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Negro o Afroamericano , Estudiantes , Humanos , Estados Unidos , UniversidadesRESUMEN
OBJECTIVE: To investigate 2- to 5-way patterns of defects co-occurring with orofacial clefts using data from a population-based registry. DESIGN: We used data from the Texas Birth Defects Registry for deliveries between 1999 and 2014 to Texas residents, including 1884 cases with cleft palate (CP) and 5289 cases with cleft lip with or without cleft palate (CL±P) without a known syndrome. We identified patterns of defects co-occurring with CP and with CL±P observed more frequently than would be expected if these defects occurred independently. We calculated adjusted observed-to-expected (O/E) ratios to account for the known tendency of birth defects to cluster nonspecifically. RESULTS: Among infants without a syndrome, 23% with CP and 21% with CL±P had at least 1 additional congenital anomaly. Several combinations of defects were observed much more often than expected. For example, the combination of CL±P, congenital hydrocephaly, anophthalmia, and other nose anomalies had an O/E ratio of 605. For both CP and CL±P, co-occurrence patterns with the highest O/E ratios involved craniofacial and brain abnormalities, and many included the skeletal, cardiovascular, and renal systems. CONCLUSIONS: The patterns of defects we observed co-occurring with clefts more often than expected may help improve our understanding of the relationships between multiple defects. Further work to better understand some of the top defect combinations could reveal new phenotypic subgroups and increase our knowledge of the developmental mechanisms that underlie the respective defects.
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Labio Leporino , Fisura del Paladar , Anomalías de la Boca , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Humanos , Lactante , SíndromeRESUMEN
BACKGROUND: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood. METHODS: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects. RESULTS: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula). CONCLUSIONS: Our analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects). IMPACT: In this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common.
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Cardiopatías Congénitas , Deformidades Congénitas de las Extremidades , Canal Anal/anomalías , Esófago/anomalías , Cardiopatías Congénitas/epidemiología , Humanos , Lactante , Riñón/anomalías , Sistema de Registros , Columna Vertebral/anomalías , Texas/epidemiología , Tráquea/anomalíasRESUMEN
Patients with chromosome 22q11.2 deletion syndromes classically present with variable cardiac defects, parathyroid and thyroid gland hypoplasia, immunodeficiency and velopharyngeal insufficiency, developmental delay, intellectual disability, cognitive impairment, and psychiatric disorders. New technologies including chromosome microarray have identified smaller deletions in the 22q11.2 region. An increasing number of studies have reported patients presenting with various features harboring smaller 22q11.2 deletions, suggesting a need to better elucidate 22q11.2 deletions and their phenotypic contributions so that clinicians may better guide prognosis for families. We identified 16 pediatric patients at our institution harboring various 22q11.2 deletions detected by chromosomal microarray and report their clinical presentations. Findings include various neurodevelopmental delays with the most common one being attention deficit hyperactivity disorder (ADHD), one reported case of infant lethality, four cases of preterm birth, one case with dual diagnoses of 22q11.2 microdeletion and Down syndrome. We examined potential genotypic contributions of the deleted regions.
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INTRODUCTION: Tension pneumoperitoneum is rarely encountered in the emergency department but can have disastrous effects on the body when it is. However, an emergency physician has skills that can be readily applied to needle decompress the abdomen for rapid stabilization. CASE REPORT: A 42-year-old male arrived via ambulance after a likely overdose with mental status improvement following naloxone administration. He was found to be in respiratory distress due to a rigid, distended abdomen that required intubation for stabilization. Computed tomography imaging showed significant pneumoperitoneum with tension physiology. Surgery consultation was unable to intervene immediately, and needle decompression with an angiocatheter was performed at the bedside with immediate ventilatory improvement. CONCLUSION: Tension pneumoperitoneum is a rare but potentially disastrous consequence of overdose secondary to emesis and rupture of the gastric wall. Needle decompression is a skillset already in the emergency physician's toolbox and can be applied for emergency stabilization of a tension pneumoperitoneum with proper forethought and technique.
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OBJECTIVE: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers. METHODS: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings. RESULTS: Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important. CONCLUSION: This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice.
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BACKGROUND: Copy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes. CASE PRESENTATION: Here we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases (case 1) and hypotonia and respiratory distress (case 2). A preliminary chromosome analysis showed normal karyotypes in both cases while the high-resolution single nucleotide polymorphism (SNP) microarray showed copy neutral absence of heterozygosity involving chromosome 15 distal long arm. In case 1, the CN-AOH involved a 28.7 Mb block from genomic coordinates 73703619_102429049. In case 2, the CN-AOH involved a 15.3 Mb block from genomic coordinates 54729197_70057534. In both cases, methylation-specific PCR did not detect an unmethylated allele for the SNRPN gene suggesting either a deletion of paternal allele or maternal UPD for chromosome 15. Since microarray analysis did not show any copy number alterations on chromosome 15, a microdeletion was ruled out. CONCLUSIONS: Based on our cases, we suggest that CN-AOH on chromosome 15, even if it does not involve the critical region of 15q12q13, should warrant additional studies for diagnosis of Prader-Willi/Angelman syndromes.
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Few population-based studies have analyzed patterns of co-occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co-occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999-2014. We calculated the observed-to-expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non-specifically. To address potential ascertainment differences among live births and non-live births, we repeated analyses specifically among live births. The combination of defects with the largest observed-to-expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed-to-expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition.
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Anomalías Múltiples/genética , Cardiopatías Congénitas/genética , Holoprosencefalia/genética , Síndrome de la Trisomía 13/genética , Anomalías Múltiples/epidemiología , Anomalías Múltiples/patología , Adolescente , Adulto , Encéfalo/patología , Niño , Preescolar , Anomalías Congénitas/epidemiología , Anomalías Congénitas/genética , Anomalías Congénitas/patología , Femenino , Asesoramiento Genético , Cardiopatías Congénitas/patología , Holoprosencefalia/patología , Humanos , Lactante , Recién Nacido , Nacimiento Vivo/epidemiología , Nacimiento Vivo/genética , Masculino , Embarazo , Texas , Síndrome de la Trisomía 13/epidemiología , Síndrome de la Trisomía 13/patología , Adulto JovenRESUMEN
INTRODUCTION: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally. OBJECTIVE: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects. STUDY DESIGN: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA). RESULTS: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias. DISCUSSION: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified. CONCLUSION: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
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Anomalías Congénitas , Hipospadias , Anomalías Congénitas/epidemiología , Genitales Masculinos , Humanos , Hipospadias/epidemiología , Lactante , Masculino , Prevalencia , Sistema de Registros , Texas/epidemiología , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.