Treatment modalities for hypospadias cripples

Hypospadias cripples can be defined as patients with remaining functional complications after previous hypospadias repair. A retrospective follow-up study was performed on the long-term results of a group of 94 patients disabled by hypospadias. The records of 94 patients showed that they presented with the following problems: 82 had a major meatal dystopia (87 percent), 43 (46 percent) had residual curvature of the penile body, 19 (20 percent) showed meatal stenosis, and only 5 (5 percent) had one or more fistulas. The techniques used to solve these problems were circumferential advancement of penile skin, dorsal transposition flap of preputial skin, distally based transposition flap of penile skin, and full-thickness skin graft. Between one and nine operations were needed to achieve the desired result (mean and median of two operations). The complications after these procedures were 11 fistulas in nine patients, meatal stenosis caused by tight scarring in six patients, and a residual curvature after an orthoplasty that had to be released once before a urethroplasty could be performed. Forty-three men were seen at long-term follow-up (range, 2 to 25 years; mean, 12 years). Functional complaints that were seen included spraying at micturition (5 patients, 12 percent), dribbling (6 patients, 14 percent), and deviation of urinary stream (7 patients, 16 percent). No patients complained of painful miction, hesitation, or straining. At physical examination, 4 patients had a residual curvature (three of which were mild without functional problems), 5 had a skin surplus, 1 presented with a fistula after an operation in another hospital, and 13 had a penile torsion. Only 6 patients had a penile torsion greater than 10 degrees, which was evenly distributed to the left and right. There was no correlation between any functional complaint and the presence of a physical abnormality.     

Parental fertility and infant hypospadias: an international case-control study.

The authors have performed an international case-control study on the significance of exogenous hormones for the origin of hypospadias (K?llén et al., 1991 a,b). Using data from this study on 846 infants with isolated hypospadias and equally many controls (next male infant born in the same hospital as the case), variables that might indicate an increased rate of fertility problems in couples who had a boy with hypospadias were studied. Cases had slightly fewer previous pregnancies, there was practically no difference in the rate of previous induced abortions, and no demonstrable difference in menstrual history. Infertility periods of at least 6 months were more likely among cases than controls but the difference did not reach statistical significance in a two-tailed test. There was no demonstrable difference in the time to conceive between cases and controls. The difficulties of directly studying subfertility problems are stressed.     

An epidermal cyst of the penis after distal hypospadias surgery: a case report

Background

Epidermoid cyst is a benign tumor that can occur anywhere in the body but is rarely seen in the penis. Congenital and previous penile surgeries have been reported to be involved in the etiology of the disease, which is usually asymptomatic. Here we describe a case of a patient with a penile epidermoid cyst, which occurred in the circumcision line on the left side of his penis, and urethral dehiscence following hypospadias surgery.

Case summary

A 3-year-old white boy who underwent primary distal hypospadias surgery 1.5?years ago presented with a slowly growing mass in the left ventrolateral portion of the penile circumcision line and urethral dehiscence. The histology of the excised mass revealed an epidermal inclusion cyst. Since then, he has remained healthy.

Conclusions

Epidermal inclusion cyst as a complication of hypospadias surgery is a very rare situation. The diagnosis is made histologically and surgical excision is sufficient for treatment.

     

Androgen binding in cultured human fibroblasts from patients with idiopathic hypospadias

Androgens stimulate development and growth of the external male genitalia. Since hypospadias represents the most common congenital abnormality in the male newborn and the mechanism of action in this disorder is still unclear, androgen binding was assessed in cultured fibroblasts from biopsies from genital skin of 10 patients with idiopathic hypospadias. For comparison, binding was determined in corresponding samples from 8 males with normal penile development and from 9 patients with known androgen resistance syndromes (testicular feminization, Reifenstein syndrome, pseudovaginal perineoscrotal hypospadias). Finally, binding was measured in 10 samples of nongenital skin. Maximum specific binding (Bmax) in idiopathic hypospadias varied from 3.2 to 15.5 (median 6.6) fmol.mg protein-1. Bmax in samples of persons with normal genital development was between 12.2 and 17.9 fmol.mg protein-1 (median 13.2). Bmax in samples of patients with known androgen resistance syndromes was exactly in the range reported previously in the literature. It is evident that Bmax in samples of patients with idiopathic hypospadias differs significantly (P less than 0.01), (Mann Whitney U-test) from those with normal genital development. Thus it seems reasonable to conclude that in some patients with idiopathic hypospadias the genital defect is caused by receptor deficiency.     

Microsurgical hypospadias repair

Successful primary hypospadias repair depends on careful execution of surgical principles, particularly during the urethroplasty portion of the procedure. These principles include careful tissue handling, development of well-vascularized flaps, and avoidance of placing sutures in the uroepithelial surface. Despite meticulous repair, the complication rate requiring secondary surgery is 15 to 30 percent. For the past year, the authors have utilized an operating room microscope, microsurgical instruments, a specially designed microsuture, and a Biooclusive dressing to decrease the postoperative morbidity and subsequent complications requiring secondary surgery (6.5 percent). A comparison of 50 hypospadias patients on whom no microsurgical repair had been used was made with 62 patients on whom microsurgical techniques were employed. The nonmicrosurgical group had 17 complications, 12 of which required reoperation (24 percent). The microsurgical group had 8 complications, 4 of which required reoperation (6.5 percent).     

Steroid 5alpha-reductase 1 polymorphisms and testosterone/dihydrotestosterone ratio in male patients with hypospadias

BACKGROUND/AIM: Defects in the steroid 5alpha-reductase type 2 (SRD5A2) activity cause decreased formation of dihydrotestosterone (DHT) from testosterone (T), resulting in defective masculinization of external genitalia; the T/DHT ratio is increased. We investigated 10 patients with elevated T/DHT ratios in whom mutations in the SRD5A2 and AR genes had been excluded to find out whether structural alterations of the SRD5A1 gene could contribute to their genital malformations. METHODS: Single-strand conformation polymorphism analysis and direct sequencing were used to detect variations in the SRD5A1 gene of the patients and of 49 adult fertile men who served as controls. RESULTS: The sequence analysis of exon 3 of the SRD5A1 gene indicated an adenine-to-guanine change (ACA vs. ACG), both triplets encoding the amino acid residue threonine. The ACG sequence was detected in 57% of all subjects and was equally distributed in patients and controls. The T/DHT ratio was significantly higher in controls with the ACG variant as compared with those having the ACA variant. However, no particular sequence aberration was found in the SRD5A1 genes of either group. CONCLUSION: Mutant SRD5A1 isoenzyme does not seem to play a crucial role in the development of hypospadias.     

The treatment of hypospadias

With recent improvements in techniques, the operative cure of hypospadias has been much improved and a satisfactory cure of this defect can be anticipated. This paper discusses the most promising types of surgical repairs and presents a method which has been particularly successful in almost 50 cases.     

Unusual presentation of biliary atresia splenic malformation syndrome with autosomal dominant hypospadias

Biliary atresia is associated with polysplenia in 2-10% of cases and is defined as Biliary Atresia Splenic Malformation syndrome (BASM). The main features of BASM syndrome include extrahepatic biliary atresia and polysplenia besides the characteristic findings of laterality anomalies, cardiac anomalies, intraabdominal vascular anomalies, pancreatic anomalies and malrotation. Here we present a 6-month-old male patient with BASM having atrial septal defect, umblical hernia, inguinal hernia, and hypospadias. Clinical history revealed that his father also had hypospadias which showed a rare form of autosomal dominant inheritance. The karyotype was normal and the molecular analysis of CFC1 gene revealed no mutation. We emphasize the importance of a detailed physical examination in cases with BASM.     

Dermatoglyphics in cases of hypospadias: New data

Data on digital and palmar dermatoglyphics in 40 males hospitalized at the Urological Clinic of the University of Cagliari are given. Data on hypospadias patients are compared to those of 106 apparently healthy Sardinian males for digital dermatoglyphics and of 180 for palmar dermatoglyphics In hypospadias patients there is a significant decrease of patterns in the hypothenar area and an increase of radial arches in hypothenar area, while for other characteristics the differences are always not significant.     

Complex segregation analysis of hypospadias

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1000 male births. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Low birth weight is known to be an important risk factor for hypospadias, but several observations speak in favour of genetic factors as well. In order to delineate the relative contribution of the genetic factors behind hypospadias, we performed a complex segregation analysis of 2005 pedigrees in Sweden. The probands were ascertained through the departments of paediatric surgery and departments of plastic surgery and urology in Sweden where boys with hypospadias undergo surgery. In 7% of the ascertained families one or more additional cases of hypospadias were present. The complex segregation analysis showed a heritability of 0.99 and evidence for multifactorial inheritance. The results suggest that hypospadias might be due to monogenic effects in a small proportion of the families, but that there is a multifactorial cause for the majority of the cases.     

Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence

This review evaluates current knowledge related to trends in the prevalence of hypospadias, the association of hypospadias with endocrine-disrupting exposures, and the potential contribution of genetic susceptibility to its etiology. The review focuses on epidemiologic evidence. Increasing prevalence of hypospadias has been observed, but such increases tend to be localized to specific regions or time periods. Thus, generalized statements that hypospadias is increasing are unsupported. Owing to the limitations of study designs and inconsistent results, firm conclusions cannot be made regarding the association of endocrine-disrupting exposures with hypospadias. Studies with more rigorous study designs (e.g., larger and more detailed phenotypes) and exposure assessment that encompasses more breadth and depth (e.g., specific endocrine-related chemicals) will be critical to make better inferences about these important environmental exposures. Many candidate genes for hypospadias have been identified, but few of them have been examined to an extent that enables solid conclusions. Further study is needed that includes larger sample sizes, comparison groups that are more representative of the populations from which the cases were derived, phenotype-specific analyses, and more extensive exploration of variants. In conclusion, examining the associations of environmental and genetic factors with hypospadias remain important areas of inquiry, although our actual understanding of their contribution to hypospadias risk in humans is currently limited.     

Molecular epidemiology of hypospadias: review of genetic and environmental risk factors

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. It is characterized by altered development of the urethra, foreskin, and ventral surface of the penis. In this review, the embryology, epidemiology, risk factors, genetic predisposition, and likely candidate genes for hypospadias are described. Recent reports have identified increases in the birth prevalence of mild and severe forms of hypospadias in the United States from the 1960s to the present. Studies in consanguineous families and small case series have identified allelic variants in genes controlling androgen action and metabolism that cause hypospadias, but the relevance of these findings to the general population is unknown. Concern has also focused on whether exposure to endocrine disrupting chemicals (EDC) with antiandrogenic activity is the cause of this increase. Hypospadias is believed to have a multifactorial etiology in which allelic variants in genes controlling androgen action and metabolism predispose individuals to develop this condition. When genetic susceptibility is combined with exposure to antiandrogenic agents, a threshold is surpassed, resulting in the manifestation of this birth defect. A clear role for exposure to antiandrogenic environmental chemicals has yet to be established in the etiology of hypospadias, although results from laboratory animal models indicate that a number of environmental chemicals could be implicated. Molecular epidemiology studies that simultaneously examine the roles of allelic variants in genes controlling androgen action and metabolism, and environmental exposures are needed to elucidate the risk factors for these anomalies and the causes of the increased rate of hypospadias.     

Role of maternal smoking and maternal reproductive history in the etiology of hypospadias in the offspring

BACKGROUND: This study was undertaken to evaluate some possible risk factors for hypospadias with special regard to parity, subfertility and maternal smoking. METHODS: With the use of the Swedish health registries, 3,262 infants with a diagnosis of hypospadias were identified among 1,413,811 infants born in 1983-96 with prospectively collected smoking exposure during pregnancy. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for various possible confounders. RESULTS: A negative association between hypospadias and maternal smoking was found (OR: 0.83 95% CI: 0.76-0.90), but this association was only observed among mothers of Parity 1 or 4+, and the possibility of the results being due to confounding was suspected. Primiparity (vs. Parity 2) was positively associated with hypospadias (OR: 1.29 95% CI: 1.19-1.40), and so was subfertility (defined here as at least 1 year of attempts to conceive) (OR for subfertility: 1.16 95% CI: 1.01-1.33). The OR for smoking and primiparity, respectively, were of the same magnitude irrespective of whether subfertility was present or not, and no evidence was found that subfertility in the parents of infants with hypospadias seriously confounded the analyses. CONCLUSIONS: No explanation was found for the negative association between maternal smoking and hypospadias or the positive association between primiparity and hypospadias. Possible causal mechanisms are discussed.     

Correlation between the birth prevalence of isolated hypospadias and parental subfertility

Factors associated with the occurrence of isolated hypospadias have been studied. We previously reported a secular trend association between hypospadias occurrence and progestagen use by the Hungarian population. Further study does not support that secular trend association. The use of progestagens for the treatment of reproductive problems is a very complex issue, and there are other factors relating to male and female fertility that differentiate the hypospadias families from the controls. It appears that families with problems of subfertility are at increased risk for the occurrence of hypospadias. Our data support more recent studies, which do not demonstrate an association between the occurrence of hypospadias and the administration of progestagens in humans.     

Intrauterine growth restriction in like-sex twins discordant for structural defects

BACKGROUND: An increased risk for intrauterine growth restriction in the affected member of like-sex twin pairs discordant for hypospadias has been reported. The purpose of this study was to document patterns of birth weight disparities in like-sex twins discordant for a variety of structural defects in order to determine if this is a general phenomenon seen in twins who are discordant for any malformation, is seen only in pairs discordant for certain specific malformations, or is unique to hypospadias. METHODS: Data were extracted from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Between 1967 and 1999, all like-sex twin pairs discordant for hypospadias or any other isolated defect that met the criteria of at least 5 discordant pairs for which birth weight was available on both twins were selected. All nonmalformed like-sex twin pairs in the ECLAMC data base collected over the same study years were selected as controls. RESULTS: A total of 216 discordant malformed like-sex twin pairs in 13 defect categories and 328 nonmalformed like-sex twin pairs met the criteria for inclusion. The proportion of affected infants who were > or =20% smaller than their co-twin was statistically significantly different from controls for hypospadias, heart defects, anencephaly, and esophageal atresia. CONCLUSIONS: Intrauterine growth restriction seen in the affected member of like-sex twin pairs discordant for hypospadias is not unique, but occurs as well in at least 3 additional structural malformations.     

阴囊纵隔血管蒂皮瓣尿道成形I期治疗尿道下裂26例

目的：介绍阴囊纵隔皮瓣尿道成形术I期修复尿道下裂的方法。方法：于阴囊纵隔部设计以纵隔血管为蒂,宽1.5～2cm,长等于尿道外口至冠状沟距离的皮瓣,切取后成形尿道,修复下裂。结果：本组26例皮瓣全部成活,成形尿道排尿通畅。术后6例出现尿漏,4例换药治疗后自行愈合,2例半年后行瘘修补。随访6月至2年,无尿瘘及尿道狭窄,阴茎功能及外形满意。结论：阴囊纵隔皮瓣尿道成形术是I期治疗尿道下裂的良好方法。     

Case control study of hypospadias, based on registry information

With the aid of data in the Swedish Medical Birth Registry for infants with hypospadias and controls, a number of variables were compared. Records of infants born in 1982-1983 (188 cases and 376 matched controls) contained information on involuntary infertility, previous spontaneous and induced abortions, use of oral contraceptives or a remaining IUD at conception, smoking in early pregnancy, occupation in early pregnancy, family situation, and diagnoses given during pregnancy and at delivery, including information on caesarean section and vacuum extraction. Among all variables studied, only one group of statistically significant differences appeared: women whose sons had hypospadias more often than controls had a diagnosis of weak contractions, a higher rate of induced deliveries, and also a higher rate of caesarean sections. The finding of a higher caesarean section rate in infants with hypospadias was verified in a separate study of 1,736 hypospadic infants delivered in 1973-1981 and compared with all births in Sweden during that period. No difference in the rate of vacuum extractions was seen. This finding is interpreted as a result of an abnormality of the fetal-placental-maternal organism interaction, perhaps also disturbing the early pregnancy and increasing the risk for hypospadias.     

T-incision technique in distal hypospadias: a modification of meatal advancement and glanuloplasty

Hypospadias is among the most common of the congenital anomalies. Distal hypospadias refers to an orifice in the distal third of the penile shaft. Correction of distal hypospadias requires different techniques, depending on the location of the meatus. Simple advancement techniques can be used for most distal hypospadias, whereas hypospadias with chordee requires reconstruction of a urethra. The meatoplasty and glanuloplasty procedures developed by Duckett have become standard operations to correct these lesions. Complications such as meatal stenosis, meatal retraction, and fish mouth-like meatus can be seen after meatal advancement and glanuloplasty ("MAGPI"), though it usually yields good results. In an attempt to avoid the complications associated with the meatal advancement and glanuloplasty procedure, the authors added a modification to the procedure for those hypospadias cases located in the coronal sulcus or its distal part. As an addition to conventional meatal advancement and glanuloplasty, a transverse incision on top of the vertical incision was made so that the urethra was supported by lateral triangle flaps created on the glans. Lateral triangle flaps of the glans were sutured to the dorsal aspect of the urethra advanced from the previous position. Thus, stress on the urethra was lessened and meatal retraction was prevented. When closure was performed with a T incision, an M-shaped, zigzag incision line was placed instead of a circular incision line. Therefore, stenosis was prevented and a vertical meatus with good cosmetic appearance was obtained. Fifty-three boys aged 4 to 7 years were operated on with this technique and were followed for 2.4 years. Good functional and cosmetic results were achieved in most of the cases.     

Urethral seam formation and hypospadias

Knowledge of the formation of the normal male urethra may elucidate the etiology of hypospadias. We describe urethral formation in the mouse, show the similarities and relevance to human urethral development, and introduce the concept of the epithelial seam formation and remodeling during urethral formation. Three mechanisms may account for epithelial seam formation: (1) epithelial-mesenchymal transformation similar to that described in the fusion of the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via cellular migration. Urethral development in the embryonic mouse (14-21 days of gestation) was compared with urethral formation in embryonic human specimens (8-16 weeks of gestation) by using histology, immunohistochemistry, and three-dimensional reconstruction. The urethra forms by fusion of the epithelial edges of the urethral folds, giving a midline epithelial seam. The epithelial seam is remodeled via cellular migration into a centrally located urethra and ventrally displaced remnant of epithelial cells. The epithelial seam is remodeled by narrowing approximately at its midpoint, with subsequent epithelial migration into the urethra or penile skin. The epithelial cells are replaced by mesenchymal cells. This remodeling seam displays a narrow band (approximately 30 microns wide) of apoptotic activity corresponding to the mesenchymal cells and not to epithelial cells. No evidence was seen of the co-expression of cytokeratin and mesenchymal markers (actin or vimentin). Urethral seam formation occurs in both the mouse and the human. Our data in the mouse support the hypothesis that seam transformation occurs via cellular migration and not by epithelial mesenchymal transformation or epithelial apoptosis. We postulate that disruption of epithelial fusion remodeling, and cellular migration leads to hypospadias.     

Aetiological studies of hypospadias in Hungary.

A complex aetiological (epidemiological, teratological and genetic) study was made in 294 index patients with simple isolated hypospadias. The epidemiological study conducted by the help of personal interviews of the mothers revealed a higher frequency of index patients among children born between August and December, among twins, mainly monozygotic, and finally in the lower birth weight groups and among first-borns. The teratological study showed a higher frequency in mothers of index patients who had had sex hormone treatment, mainly progestogen, before the 16th gestational week. This seems to indicate the aetiological role of fetal androgen deficit caused by the regulation disturbances of human choriogonadotropin. The genetic family study completed by personal examination of first-degree male relatives showed a familial clustering (4.0% versus a point prevalence of 0.44% in live-births). Both the pattern of affected relatives (h2 values 0.62 +/- 0.21 and 0.72 +/- 0.33 in fathers and brothers, respectively, not differing significantly from each other) and further characteristics (other malformations were not frequent in relatives) correspond to the multifactorial-threshold model.