Development of a prediction model for postoperative complications after primary hypospadias correction.

Purpose: To develop a prediction model for postoperative complications after primary one-stage hypospadias correction to improve preoperative parental counseling.

Materials And Methods: In this retrospective cohort study, data were collected from 356 patients with anterior or middle hypospadias who had a one-stage hypospadias correction from 2003 onwards. Potential treatment- and patient-related factors were selected and used to develop a prediction model for postoperative complications within one year (wound-related complications, urinary tract infections, fistulas, stenosis, and prepuce-related complications).

Level of agreement on postoperative complications after one-stage hypospadias correction comparing medical records and parent reports.

Purpose: To analyze agreement on postoperative complications after hypospadias surgery according to medical records and parents' reports.

Materials & Methods: In this retrospective cohort study, data were collected from 409 children who received an initial one-stage hypospadias correction in the Radboudumc, The Netherlands. Postoperative complications according to medical records were compared with parent-reported complications in an online questionnaire.

Previous miscarriages and GLI2 are associated with anorectal malformations in offspring.

Study Question: Are anorectal malformations (ARMs) associated with previous miscarriages or single nucleotide polymorphisms (SNPs) in the Bone Morphogenetic Protein 4 (BMP4) and GLI family zinc finger 2 (GLI2) genes?

Summary Answer: The SNP rs3738880 in GLI2 and miscarriages were associated with ARM, especially in patients with multiple congenital anomalies (MCA).

What Is Known Already: ARM are one of the most common birth defects of the gastrointestinal tract. The etiology is likely to be multifactorial, involving both environmental and genetic factors.

AGORA, a data- and biobank for birth defects and childhood cancer.

Background: Research regarding the etiology of birth defects and childhood cancer is essential to develop preventive measures, but often requires large study populations. Therefore, we established the AGORA data- and biobank in the Netherlands. In this study, we describe its rationale, design, and ongoing data collection.

Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: A case-control study.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous group of birth defects with a variety of genetic and nongenetic factors suspected of involvement in the etiology. However, little is known about risk factors in specific CAKUT phenotypes. Therefore, we studied potential maternal risk factors in individual phenotypes within the CAKUT spectrum.

Interaction between MTHFR 677C>T and periconceptional folic acid supplementation in the risk of Hypospadias.

Background: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the development of hypospadias is unclear. As folate levels may also be influenced by the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, we hypothesize that a gene-environment interaction between this polymorphism and folic acid use is involved in the etiology of hypospadias.

Sequencing of the DKK1 gene in patients with anorectal malformations and hypospadias.

Unlabelled: Anorectal malformations (ARM) are rare congenital malformations of the gastrointestinal tract. Approximately 60% of the patients have additional congenital malformations, such as hypospadias. A recently published article showed that deletion of one single gene, dickkopf WNT signaling pathway inhibitor-1 (Dkk1), resulted in an imperforate anus with rectourinary fistula and preputial hypospadias in mice.

Genome-wide association analyses identify variants in developmental genes associated with hypospadias.

Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1,812 controls from Denmark, the Netherlands and Sweden, 18 genomic regions showed independent association with P < 5 × 10(-8).

Fine mapping analysis confirms and strengthens linkage of four chromosomal regions in familial hypospadias.

Hypospadias is a common male genital malformation and is regarded as a complex disease affected by multiple genetic as well as environmental factors. In a previous genome-wide scan for familial hypospadias, we reported suggestive linkage in nine chromosomal regions. We have extended this analysis by including new families and additional markers using non-parametric linkage.

No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations.

Background: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM.

A common variant at 8q24.21 is associated with renal cell cancer.

Renal cell carcinoma (RCC) represents between 80 and 90% of kidney cancers. Previous genome-wide association studies of RCC have identified five variants conferring risk of the disease. Here we report the results from a discovery RCC genome-wide association study and replication analysis, including a total of 2,411 patients and 71,497 controls.

Risk factors for different phenotypes of hypospadias: results from a Dutch case-control study.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The various phenotypes of hypospadias may result from disturbances of dissimilar embryonic processes in different time windows, suggesting aetiological heterogeneity; however, only a few studies have investigated the risk factors for the different hypospadias phenotypes. The study confirmed that genetic predisposition possibly plays a role in anterior and middle hypospadias, as shown by the large effect estimates for familial occurrence of these forms of hypospadias. By contrast, the posterior phenotype was more often associated with pregnancy-related factors, such as primiparity, preterm delivery, and being small for gestational age.

Exploration of gene-environment interactions, maternal effects and parent of origin effects in the etiology of hypospadias.

Purpose: Hypospadias is a common congenital malformation of the male external genitalia. Association studies for single nucleotide polymorphisms in genes encoding steroid 5alpha-reductase, estrogen receptors 1 and 2, and activating transcription factor 3 have been equivocal. We examined whether nonreplication of findings for 4 single nucleotide polymorphisms in these genes could be due to interaction with environmental exposures.

Common variants in DGKK are strongly associated with risk of hypospadias.

Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.

Genetics of hypospadias: are single-nucleotide polymorphisms in SRD5A2, ESR1, ESR2, and ATF3 really associated with the malformation?

Context: Hypospadias is a common congenital malformation of the male external genitalia with a multifactorial etiology. Little is known about the genes involved in hypospadias. A few genetic associations have been reported but mainly in studies of small sample size.

Hypospadias: risk factor patterns and different phenotypes.

Objective: To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes.

Patients And Methods: Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43).