Talk:Genital Abnormality - Hypospadias

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Cite this page: Hill, M.A. (2020, November 28) Embryology Genital Abnormality - Hypospadias. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Genital_Abnormality_-_Hypospadias

2019

2018

Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012

J Pediatr Urol. 2018 Oct;14(5):425.e1-425.e7. doi: 10.1016/j.jpurol.2018.08.024. Epub 2018 Sep 19.

Chen MJ1, Karaviti LP1, Roth DR2, Schlomer BJ3.

Abstract

BACKGROUND: Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. OBJECTIVE: The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. STUDY DESIGN: The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. RESULTS: The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). CONCLUSIONS: The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Hypospadias; Multiple gestation; Premature birth; Small for gestational age PMID: 30322769 DOI: 10.1016/j.jpurol.2018.08.024

Somatically Acquired Isodicentric Y and Mosaic Loss of Chromosome Y in a Boy with Hypospadias

Cytogenet Genome Res. 2018 Apr 7. doi: 10.1159/000488162. [Epub ahead of print]

Miyado M, Muroya K, Katsumi M, Saito K, Kon M, Fukami M.

Abstract

Isodicentric Y chromosome [idic(Y)] represents a relatively common subtype of Y chromosomal rearrangements in the germline; however, limited evidence supports the postzygotic occurrence of idic(Y). Here, we report a boy with hypospadias and somatically acquired idic(Y). The 3.5-year-old boy has been identified in our previous study for patients with hypospadias. In the present study, cytogenetic analysis including FISH revealed a 45,X[5]/46,X,idic(Y)[7]/46,XY[8] karyotype. MLPA showed a mosaic deletion involving PPP1R12BP1 and RBMY2DP. The idic(Y) was likely to have been formed through aberrant recombination between P1 palindromes and subsequently underwent mosaic loss. The patient's phenotype was attributable to deletion of some Y chromosomal genes and/or mosaic loss of chromosome Y (mLOY). The results suggest that idic(Y) can originate in postzygotic cells via palindrome-mediated crossovers. Moreover, our data indicate that somatically acquired idic(Y) can trigger mLOY, which usually appears as an aging-related phenomenon in elderly men. KEYWORDS: Mitosis; Mosaic karyotype; Palindrome; Recombination; Y chromosome PMID: 29627832 DOI: 10.1159/000488162

2015

Genetic and environmental factors in the aetiology of hypospadias

Pediatr Surg Int. 2015 Jun;31(6):519-27. doi: 10.1007/s00383-015-3686-z. Epub 2015 Mar 6.

George M1, Schneuer FJ, Jamieson SE, Holland AJ.

Abstract

This article reviews the current evidence and knowledge of the aetiology of hypospadias. Hypospadias remains a fascinating anomaly of the male phallus. It may be an isolated occurrence or part of a syndrome or field defect. The increasing use of assisted reproductive techniques and hormonal manipulation during pregnancy may have been associated with an apparent rise in the incidence of hypospadias. Genetic studies and gene analysis have suggested some defects that could result in hypospadias. New light has also been thrown on environmental factors that could modulate candidate genes, causing altered development of the male external genitalia.

PMID 25742936

Current understanding of hypospadias: relevance of animal models

Nat Rev Urol. 2015 May;12(5):271-280. doi: 10.1038/nrurol.2015.57. Epub 2015 Apr 7. Cunha GR1, Sinclair A1, Risbridger G2, Hutson J3, Baskin LS1.

Abstract

Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.

PMID 25850792


Surgical anatomy of the penis in hypospadias: magnetic resonance imaging study of the tissue planes, vessels, and collaterals

Urology. 2015 May;85(5):1173-8. doi: 10.1016/j.urology.2015.02.017.

Kureel SN1, Gupta A2, Sunil K2, Dheer Y2, Kumar M3, Tomar VK4.

Abstract

OBJECTIVE: To report the surgical anatomy of the penis in hypospadias with study of vessels in relation to fascial planes, glans, corpora cavernosa, and corpus spongiosum using magnetic resonance imaging. MATERIALS AND METHODS: Twelve hypospadias presenting at older age (8-20 years) were studied with 1.5-T magnetic resonance imaging scanner and a 3-inch surface coil. Precontrast and postcontrast images were acquired using fast-spin echo sequences in sagittal, coronal, and transverse planes. The findings were processed in Volume Share 4.5, version Workstation, of General Electric Healthcare. Anatomic findings were verified during surgery. With imaging and surgical findings, a 3-dimensional conceptual diagram of surgical anatomy was created. RESULTS: Distinct layers of the skin, dartos fascia, Buck fascia, tunica albuginea, glans urothelium, lamina propria of glans, and corpus spongiosum were delineated with their spatial relationship. Axial pattern vessels of the dartos and its anastomosis with branches of dorsal penile vessels at the coronal sulcus, perforators along the corpus spongiosum, subglanular extension of the fascia, and intraglanular branches of the dorsal penile artery forming an arcade were visualized. CONCLUSION: Dorsomedial and dorsolateral axial pattern vessels are present in penile dartos with relative avascularity at dorsal midline in most cases. Subglanular extension of Buck fascia fused with the basal lamina propria of glans forms a barrier between the tip of corpora and the intraglanular arcade of vessels. Collaterals are present at coronal sulcus, along the bifurcated corpus spongiosum, and the dartos enabling blood flow between the terminal most branches of the external and internal pudendal vessels. Copyright © 2015 Elsevier Inc. All rights reserved.

PMID 25917735

2012

Soft tissue covers in hypospadias surgery: Is tunica vaginalis better than dartos flap?

J Indian Assoc Pediatr Surg. 2012 Jan;17(1):16-9. doi: 10.4103/0971-9261.91080.

Dhua AK1, Aggarwal SK, Sinha S, Ratan SK.

Abstract AIM: To compare tunica vaginalis with dartos flap as soft tissue cover in primary hypospadias repair. MATERIALS AND METHODS: 25 cases (age range: 12-132 months; all fresh cases) of primary hypospadias were prospectively repaired by tubularized incised plate (TIP)/TIP + graft urethroplasty using tunica vaginalis flap (TVF) as soft tissue cover to urethroplasty (group A). Their results were compared with another set (group B) of age- and anatomy-matched controls (25 patients operated during the previous 3 years) who had undergone TIP repair using dartos flap as soft tissue cover. Statistical analysis of results was done with Fischer's exact test. RESULTS: GROUP A: No fistula, skin necrosis, meatal stenosis, urethral stricture. One case had partial wound dehiscence that resolved on conservative treatment with no sequelae. One case required catheter removal on 3(rd) day because of severe bladder spasm. There was no testicular atrophy/ascent. Group B: 3 fistulae - all required surgery. There were three cases of superficial skin necrosis that healed spontaneously without sequel. There was no meatal stenosis/urethral stricture. The difference in fistula rate between both the groups, however, was not statistically significant (P = 0.4). CONCLUSION: TVF may have an edge over dartos fascia for soft tissue coverage of the neourethra. KEYWORDS: Dartos fascia; hypospadias; tunica vaginalis flap; urethrocutaneous fistula

PMID 22279358

2008

Placental insufficiency in early gestation is associated with hypospadias

J Pediatr Surg. 2008 Feb;43(2):358-61. doi: 10.1016/j.jpedsurg.2007.10.046.

Fujimoto T1, Suwa T, Kabe K, Adachi T, Nakabayashi M, Amamiya T.

Abstract

BACKGROUND AND PURPOSE: The association of growth retardation and hypospadias is well established. Fetal testosterone secretion is under the influence of placental human chorionic gonadotropin during first 14 weeks of gestation. We hypothesized that placental insufficiency may disrupt the supply of nutrients and human chorionic gonadotropin to the fetus leading to both growth retardation and hypospadias. To validate this hypothesis, we analyzed extremely low-birth-weight male infants with or without hypospadias for fetal growth parameters. MATERIALS AND METHODS: One hundred four male newborn infants with birth body weight of less than 1500 g admitted to a neonatal intensive care unit over a 4-year period were retrospectively reviewed, recording the presence and type of hypospadias, fetal growth parameters, infant growth parameters at birth, placental weight, placental histopathology, cord information, and maternal morbidity. These data of patients with hypospadias were compared with those of controls. RESULTS: Of the 104 extremely to very low-birth-weight male infants, 16 (15.3%) had hypospadias, and 10 (62.5%) of those had severe proximal hypospadias. Sixty-two controls who did not have hypospadias and whose body weight was less than 1500 g were identified. The incidence of hypospadias in full-term male birth in the hospital was 12 (0.30%) in 3959 births. Birth body weight and their SD for gestational age were lower in patients with hypospadias compared with those for controls (824 +/- 160 vs 1255 +/- 145 g). Placenta-to-fetal ratio (0.323 +/- 0.07 vs 0.229 +/- 0.03) and gestational age were significantly higher in the patients with hypospadias. Histopathologic study of the maternal placenta obtained from the patients with hypospadias revealed pronounced degenerative changes, infarction, and calcification, whereas these abnormalities were rare in controls. CONCLUSIONS: The significant association between the occurrence of hypospadias and early growth retardation with higher placenta-to-fetal ratio and placental abnormalities suggest that placental dysfunction in early gestation may play an important role in the development of hypospadias. PMID 18280290