Urogenital Defects Research Articles

Functional equivalence of the zinc finger transcription factors Osr1 and Osr2 in mouse development

Osr1 and Osr2 are the only mammalian homologs of the Drosophila odd-skipped family developmental regulators. The Osr1 protein contains three zinc-finger motifs whereas Osr2 exists in two isoforms, containing three and five zinc-finger motifs respectively, due to alternative splicing of the transcripts. Targeted null mutations in these genes in mice resulted in distinct phenotypes, with heart and urogenital developmental defects in Osr1−/− mice and with cleft palate and open eyelids at birth in Osr2−/− mice. To investigate whether these contrasting mutant phenotypes are due to differences in their protein structure or to differential expression patterns, we generated mice in which the endogenous Osr2 coding region was replaced by either Osr1 cDNA or Osr2A cDNA encoding the five-finger isoform. The knockin alleles recapitulated endogenous Osr2 mRNA expression patterns in most tissues and completely rescued cleft palate and cranial skeletal developmental defects of Osr2−/− mice. Mice hemizygous or homozygous for either knockin allele exhibited open-eyelids at birth, which correlated with differences in expression patterns between the knockin allele and the endogenous Osr2 gene during eyelid development. Molecular marker analyses in Osr2−/− and Osr2Osr1ki/Osr1ki mice revealed that Osr2 controls eyelid development through regulation of the Fgf10–Fgfr2 signaling pathway and that Osr1 rescued Osr2 function in maintaining Fgf10 expression during eyelid development in Osr2Osr1ki/Osr1ki mice. These results indicate that the distinct functions of Osr1 and Osr2 during mouse development result from evolutionary divergence of their cis regulatory sequences rather than distinct biochemical activities of their protein products.

Indoor Residual Spraying (IRS) with DDT is Associated with Urogenital Birth Defects in Newborn Venda Boys from South Africa

Indoor Residual Spraying (IRS) with DDT is Associated with Urogenital Birth Defects in Newborn Venda Boys from South Africa

Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis/hypogenesis

Background:Patients with a microscopically visible deletion of the distal part of the long arm of chromosome 1 have a recognisable phenotype, including mental retardation, microcephaly, growth retardation, a distinct facial...

Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria

Fraser syndrome is an autosomal recessive congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects. We studied the clinical features in 59 affected individuals from 40 families (25 consanguineous), and compared our findings to data from previous reviews. We found a higher frequency of abnormalities of the skull, larynx, umbilicus, urinary tract, and anus in our series of patients, and mental retardation and cleft lip with or without cleft palate were observed less frequently than previously reported. Clinical features in probands and sibs were remarkably similar. As can be expected prenatally diagnosed patients had more manifestations that gave rise to a pathological amount of amniotic fluid. Otherwise patients diagnosed before and after birth had similar frequencies of symptoms. Based on the present results we suggest an adaptation of diagnostic criteria for FS, including adding airway tract and urinary tract anomalies as major criteria. The specificity of the proposed diagnostic criteria was evaluated using the London Medical Database as a search tool.

Abnormal urethra formation in mouse models of Split-hand/split-foot malformation type 1 and type 4

Urogenital birth defects are one of the common phenotypes observed in hereditary human disorders. In particular, limb malformations are often associated with urogenital developmental abnormalities, as the case for Hand-foot-genital syndrome displaying similar hypoplasia/agenesis of limbs and external genitalia. Split-hand/split-foot malformation (SHFM) is a syndromic limb disorder affecting the central rays of the autopod with median clefts of the hands and feet, missing central fingers and often fusion of the remaining ones. SHFM type 1 (SHFM1) is linked to genomic deletions or rearrangements, which includes the distal-less-related homeogenes DLX5 and DLX6 as well as DSS1. SHFM type 4 (SHFM4) is associated with mutations in p63, which encodes a p53-related transcription factor. To understand that SHFM is associated with urogenital birth defects, we performed gene expression analysis and gene knockout mouse model analyses. We show here that Dlx5, Dlx6, p63 and Bmp7, one of the p63 downstream candidate genes, are all expressed in the developing urethral plate (UP) and that targeted inactivation of these genes in the mouse results in UP defects leading to abnormal urethra formation. These results suggested that different set of transcription factors and growth factor genes play similar developmental functions during embryonic urethra formation. Human SHFM syndromes display multiple phenotypes with variations in addition to split hand foot limb phenotype. These results suggest that different genes associated with human SHFM could also be involved in the aetiogenesis of hypospadias pointing toward a common molecular origin of these congenital malformations.

Indoor Residual Spraying (IRS) of DDT Is Associated With Urogenital Birth Defects in Neonates

ISEE-374 Objective: To determine the risk of urogenital birth defects in newborn babies to mothers living in DDT-sprayed houses, Limpopo Province, South Africa. Material and Methods: The study was performed at Tshilidzini Hospital, Thohoyandou, Limpopo Province, where DDT has been used since 1945 for malaria vector control. From May 2004 to April 2006, 2 trained professional nurses examined 7145 newborn babies for external urogenital birth defects. Anomalies were coded as definite only if a pediatrician or the Genetics Nurse confirmed the diagnosis. The cross-sectional study included 2640 children from DDT-sprayed villages and 4299 children from similar ethnic and socioeconomic backgrounds living in nonsprayed villages (reference group). The reference group was newborns from nonsprayed villages. Results: Of the 7145 newborns examined, 5.66% had external urogenital anomalies, whereas defects occurred in 55.6/1000 livebirths. The presence of urogenital birth defects was influenced by whether the mother was living in a DDT-sprayed village (P = 0.028) and the presence of polythelia (P = 0.000) (Pearson χ2 tests). Estimated risk ratios showed that children living in sprayed villages were 1.75 times more at risk in comparison to those from nonsprayed villages. Likewise, children with extra nipples were 3.38 times more at risk to have urogenital birth defects in comparison with children with no extra nipples. Stratum-specific odds ratios for occupation showed that being unemployed or a scholar/student increased the risk. Conclusions: Maternal exposure by living in a DDT-sprayed village significantly increased the risk of having offspring with 1 or more urogenital birth defects. Moreover, spending more time at home seemed to further increase the risk. Integrating adequate IRS measures from the malaria control program and increased awareness on the need for self-protection by the residents are crucial components that need to be addressed. Monitoring the impact of IRS on human and environmental health is imperative if DDT is used or reintroduced.

Pallister-Killian Syndrome Presenting With a Complex Congenital Heart Defect and Increased Nuchal Translucency

Journal of Ultrasound in MedicineVolume 25, Issue 11 p. 1475-1480 Case Report Pallister-Killian Syndrome Presenting With a Complex Congenital Heart Defect and Increased Nuchal Translucency David Escribano Abad MD, David Escribano Abad MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this authorJuan Arbués Gabarre MD, Juan Arbués Gabarre MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this authorAna Moreno Izquierdo MD, Corresponding Author Ana Moreno Izquierdo MD [email protected] Human Genetics Unit, Hospital Universitario 12 de Octubre, Madrid, SpainAddress correspondence to Alberto Galindo Izquierdo, MD, Servicio de Obstetricia y Ginecología, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain.Search for more papers by this authorCarmen López-Sánchez PhD, Carmen López-Sánchez PhD Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.Search for more papers by this authorVirginio García-Martínez MD, PhD, Virginio García-Martínez MD, PhD Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.Search for more papers by this authorAlberto Galindo Izquierdo MD, Alberto Galindo Izquierdo MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this author David Escribano Abad MD, David Escribano Abad MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this authorJuan Arbués Gabarre MD, Juan Arbués Gabarre MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this authorAna Moreno Izquierdo MD, Corresponding Author Ana Moreno Izquierdo MD [email protected] Human Genetics Unit, Hospital Universitario 12 de Octubre, Madrid, SpainAddress correspondence to Alberto Galindo Izquierdo, MD, Servicio de Obstetricia y Ginecología, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain.Search for more papers by this authorCarmen López-Sánchez PhD, Carmen López-Sánchez PhD Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.Search for more papers by this authorVirginio García-Martínez MD, PhD, Virginio García-Martínez MD, PhD Department of Human Anatomy and Embryology, Faculty of Medicine, University of Extremadura, Badajoz, Spain.Search for more papers by this authorAlberto Galindo Izquierdo MD, Alberto Galindo Izquierdo MD Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Madrid, SpainSearch for more papers by this author First published: 01 November 2006 https://doi.org/10.7863/jum.2006.25.11.1475Citations: 10Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume25, Issue11November 2006Pages 1475-1480 RelatedInformation

Mutations in PHD‐like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome

Mutations in ATRX are associated with a wide and clinically heterogeneous spectrum of X-linked mental retardation syndromes. The ATRX protein, involved in chromatin remodelling, belongs to the family of SWI/SNF DNA helicases and contains a plant homeodomain (PHD)-like domain. To date, more than 60 different mutations have been reported in ATRX. One of them is recurrent and accounts for 20% of all the reported mutations, whereas all others are private. Most mutations are clustered in the two major functional domains, the helicase and the PHD-like domain. So far, no clear genotype-phenotype correlation has been established, with exception to the rare truncating mutations located at the C-terminal part of the protein, which are consistently associated with severe urogenital defects. In this study, we report the molecular analysis performed in 16 families positive for ATRX. Our findings indicate that, in addition to the previously described mutation 'hotspot' in the PHD-like domain, two other protein sections emerge as minor 'hotspots' in the helicase region encoded by exons 18-20 and 26-29, respectively, gathering 33% of all described mutations. Additionally, based on the clinical data collected for 22 patients from the 16 families, we observe that mutations in the PHD-like domain produce severe and permanent psychomotor deficiency, usually preventing patients from walking, as well as constant urogenital abnormalities, while mutations in the helicase domain lead to delayed but correct psychomotor acquisitions together with mild or absent urogenital abnormalities. In summary, mutations in the helicase domain are associated with milder phenotypes than mutations in the PHD-like domain.

Anorectal malformations in children

<b>Background/Purpose: </b> Anorectal malformations are one of the most common congenital defects. This study was undertaken to study the hospital incidence of anorectal malformations (ARM), frequency of various types of defects, their sex distribution and the spectrum of anomalies associated with ARM. The effect of presence of an associated defect on mortality and morbidity was also studied.<br><b> Materials and Methods:</b> One hundred consecutive children attending the pediatric surgery department were included in this study. A detailed history was taken, and examination was performed for the primary as well as the associated defects. Appropriate investigations like invertogram, cologram were done wherever indicated. Management was as per the standard protocol. The data was recorded and analyzed. <br><b> Results:</b> Out of the 100 patients, 51 were males and 49 females. One out of every 6.62 admission was for ARM. Twenty percent of the female babies had high, 76% intermediate and 4% had low anomalies, whereas 80.39% males had high, 3.92% intermediate and 15.6% showed low malformations. Ten percent of the patients had pouch colon. Associated anomalies were seen in 33 patients - 20 males and 13 females; 19 in high, 10 in intermediate, 1 in low group and 3 children with cloacal malformations. Associated defects seen were urogenital (17%), cardiovascular (7%), gastrointestinal (9%), genital (5%) and limb defects (7%). There were 8 deaths, and complications were seen in 13 patients. Ten patients had two or more defects associated with ARM.<br><b> Conclusions:</b> Anorectal malformations occurred equally in males and females. Females had intermediate defects more frequently, rectovestibular fistula being the commonest. Males were more likely to have high lesions; anorectal agenesis without fistula was the commonest defect. The most common associated defects seen were vesicoureteric reflux and esophageal atresia. Complications were seen more commonly in males with high lesions. There was a significant association between presence of an associated defect and mortality and morbidity.

A report of three patients with an interstitial deletion of chromosome 15q24

Partial monosomy of the q2 region of chromosome 15 has been infrequently reported. Moreover, interstitial deletions involving 15q22-q24 have been described in only nine patients to date. The phenotype of these reported individuals is subject to the extent of the deletion but typically includes altered muscle tone and significant developmental delays. In addition, eye abnormalities, such as strabismus, microphthalmia, or colobomas, ear abnormalities including cleft earlobe and preauricular tags, and urogenital defects are common features. Congenital heart defects, diaphragmatic hernia, abnormalities of the central nervous system, and skeletal anomalies have been reported but appear to be less frequent clinical manifestations. In this report, we describe three new patients with interstitial deletions involving 15q24, two with cryptic deletions identified by fluorescence in situ hybridization (FISH) with a probe for the PML gene and one with a cytogenetically visible deletion of 15q22.3-q24. The clinical presentation of these individuals is similar to those previously described and includes global developmental delays, hypotonia, and genital abnormalities in the males. The identification of these three cases demonstrates that the above clinical features are associated with a new cytogenetic deletion syndrome. Furthermore, we suggest that FISH analysis with a probe for the PML gene be performed in patients with these physical findings.

A morpho-etiological description of congenital limb anomalies

BACKGROUNDLimb anomalies rank behind congenital heart disease as the most common birth defects observed in infants. More than 50 classifications for limb anomalies based on morphology and osseous anatomy have been drafted over the past 150 years. The present work aims to provide a concise summary of the most common congenital limb anomalies on a morpho-etiological basis.PATIENTS AND METHODSIn a retrospective study, 70 newborns with anomalies of the upper and/or lower limbs were ascertained through clinical examination, chromosomal analysis, skeletal surveys and other relevant investigations.RESULTSFetal causes of limb anomalies represented 55.8% of the cases in the form of 9 cases (12.9%) with chromosomal aberrations (trisomy 13, 18 and 21, duplication 13q and deletion 22q) and 30 cases (42.9%) with single gene disorders. An environmental etiology for limb anomalies was diagnosed in 11 cases (15.7%) as amniotic band disruption, monozygotic twin with abnormal circulation, vascular disruption (Poland sequence, sirenomelia and general vascular disruption) and an infant with a diabetic mother. Twenty cases (28.5%) had limb anomalies as part of sporadic syndromes of unknown etiology.CONCLUSIONSThe morpho-etiological work-up of limb anomalies adopted in the present study is valuable for detecting the cause of the anomaly and is crucial for its prevention. Prevention can be achieved by proper genetic counseling, which includes recurrence risk estimation and prenatal diagnosis.

Genetic predisposition to testicular germ-cell tumours: Lutke Holzik MF, Rapley EA, Hoekstra HJ, Sleijfer DT, Nolte IM, Sijmons RH, Department of Surgical Oncology, Groningen University Medical Centre, Groningen, Netherlands.

Testicular germ-cell tumours (TGCT) are the most common neoplasm in young men. Various studies have suggested the existence of an inherited predisposition to development of these tumours. Genome-wide screens subsequently provided evidence of a TGCT susceptibility gene on chromosome Xq27 ( TGCT1 ) that might also predispose to cryptorchism. However, this putative gene has yet to be identified, and other TGCT susceptibility genes probably exist. Completion of the human gene map and advances in genetic research will facilitate further investigation of genetic predisposition to TGCT. Insight into inheritance of TGCT might lead to the identification of individuals at increased risk of developing the disorder, increase our understanding of the mutation pathways that lead to sporadic cases, and contribute to improvement in diagnosis and treatment. Clinicians should record the family history of cancer and urogenital differentiation defects in patients with TGCT.

Mutations in SRY and WT1 genes required for gonadal development are not responsible for XY partial gonadal dysgenesis

The WT1 transcription factor regulates SRY expression during the initial steps of the sex determination process in humans, activating a gene cascade leading to testis differentiation. In addition to causing Wilms' tumor, mutations in WT1 are often responsible for urogenital defects in men, while SRY mutations are mainly related to 46,XY pure gonadal dysgenesis. In order to evaluate their role in abnormal testicular organogenesis, we screened for SRY and WT1 gene mutations in 10 children with XY partial gonadal dysgenesis, 2 of whom with a history of Wilms' tumor. The open reading frame and 360 bp of the 5' flanking sequence of the SRY gene, and the ten exons and intron boundaries of the WT1 gene were amplified by PCR of genomic DNA. Single-strand conformation polymorphism was initially used for WT1 mutation screening. Since shifts in fragment migration were only observed for intron/exon 4, the ten WT1 exons from all patients were sequenced manually. No mutations were detected in the SRY 5' untranslated region or within SRY open-reading frame sequences. WT1 sequencing revealed one missense mutation (D396N) in the ninth exon of a patient who also had Wilms' tumor. In addition, two silent point mutations were found in the first exon including one described here for the first time. Some non-coding sequence variations were detected, representing one new (IVS4+85A>G) and two already described (-7ATG T>G, IVS9-49 T>C) single nucleotide polymorphisms. Therefore, mutations in two major genes required for gonadal development, SRY and WT1, are not responsible for XY partial gonadal dysgenesis.

Correction of Facial Deformity Using a Red III Device in a Patient With Antley-Bixler Syndrome

Antley-Bixler syndrome was first described in 1975 and to date at least 44 cases have been reported. In addition to brachycephaly, this syndrome is associated with midface hypoplasia, bilateral radiohumeral synostosis, multiple joint contractures, long bone fractures, dysplastic ears, "pear shaped" nose, and occasionally urogenital or cardiac defects. The authors report a case in a 23-year-old man with severe midface deficiency treated using distraction osteogenesis. A modified Le Fort III osteotomy was performed, and nasal subunit and remaining Le Fort III segment was distracted separately. The classic RED II design was found to be insufficient, so the authors added an extra horizontal bar to the system and converted it to a RED III design. Midface advancement was 11 mm from the porion to the orbitale and 31 mm at point A. Nasal advancement at the nasal root level was 5 mm. There were no complications, and at 4 months after surgery, advancement was stable without any relapse.

A rare coexistence of urogenital anomalies, anorectal atresia and skeletal defects

A rare coexistence of urogenital anomalies, anorectal atresia and skeletal defects

Lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad development in C. elegans

In screens for genetic modifiers of lin-35/Rb, the C. elegans retinoblastoma protein (Rb) homolog, we have identified a mutation in xnp-1. Mutations in xnp-1, including a presumed null allele, are viable and, in general, appear indistinguishable from the wild type. In contrast, xnp-1 lin-35 double mutants are typically sterile and exhibit severe defects in gonadal development. Analyses of the abnormal gonads indicate a defect in the lineages that generate cells of the sheath and spermatheca. xnp-1 encodes the C. elegans homolog of ATR-X, a human disease gene associated with severe forms of mental retardation and urogenital developmental defects. xnp-1/ATR-X is a member of the Swi2/Snf2 family of ATP-dependent DEAD/DEAH box helicases, which function in nucleosome remodeling and transcriptional regulation. Expression of an xnp-1∷GFP promoter fusion is detected throughout C. elegans development in several cell types including neurons and cells of the somatic gonad. Our findings demonstrate a new biological role for Rb family members in somatic gonad development and implicate lin-35 in the execution of multiple cell fates in C. elegans. In addition, our results suggest a possible conserved function for xnp-1/ATR-X in gonadal development across species.

Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family

Tetra-amelia is a rare human genetic disorder characterized by complete absence of all four limbs and other anomalies. We studied a consanguineous family with four affected fetuses displaying autosomal recessive tetra-amelia and craniofacial and urogenital defects. By homozygosity mapping, the disease locus was assigned to chromosome 17q21, with a maximum multipoint LOD score of 2.9 at markers D17S931, D17S1785, D17SS1827, and D17S1868. Further fine mapping defined a critical interval of approximately 8.9 Mb between D17S1299 and D17S797. We identified a homozygous nonsense mutation (Q83X) in the WNT3 gene in affected fetuses of the family. WNT3, a human homologue of the Drosophila wingless gene, encodes a member of the WNT family known to play key roles in embryonic development. The Q83X mutation truncates WNT3 at its amino terminus, suggesting that loss of function is the most likely cause of the disorder. Our findings contrast with the observation of early lethality in mice homozygous for null alleles of Wnt3. To our knowledge, this is the first report of a mutation in a WNT gene associated with a Mendelian disorder. The identification of a WNT3 mutation in tetra-amelia indicates that WNT3 is required at the earliest stages of human limb formation and for craniofacial and urogenital development.

The Adrenocortical Dysplasia (acd) Mouse: Mutation in a Novel Gene Causes a Pleiotropic Phenotype of Urogenital Defects and Caudal Dysgenesis

The adrenocortical dysplasia (DW/J‐acd/J) mouse is a spontaneous autosomal recessive mutant with developmental defects in organs derived from the urogenital ridge: the kidneys, gonads, and adrenals. Adrenocortical dysplasia and hypofunction are predominant features in surviving adult mice. Adult female mutant mice exhibit subnormal fertility secondary to an overall decrease in folliculogenesis in the ovary, and males are completely infertile due to germ cell degeneration in the testes. Fifty percent of adult acd mutant mice develop hydronephrosis due to ureteral hyperplasia. On the original genetic background, most mutants die within 1–2 days of life. Analysis of acd mutant embryos on this genetic background reveals variable, yet striking defects in caudal specification, limb patterning, and axial skeletal formation. We have identified a splice donor site mutation in a novel gene (Acd) in acd mutant mice. Characterization of Acd transcripts produced in acd mutant tissues reveals two abnormal transcripts and lack of any detectable normal transcript, consistent with a splicing defect. Expression of a beta‐actin‐driven Acd cDNA transgene rescues the mutant phenotype and provides genetic confirmation of the etiologic role of the Acd gene in the observed adrenal dysplasia. Surprisingly, the Acd gene is the mouse ortholog of a newly discovered telomeric regulator, which has recently been characterized by others as a novel component of the protein complex that controls telomere elongation by telomerase. Further studies are in progress to evaluate for evidence of genomic instability in acd mutant animals and to define the molecular mechanisms leading to urogenital and caudal dysgenesis in acd mutant embryos.

Atresia ani with diphallus and separate scrota in a calf: a case report

Atresia ani, a common genetic defect in animals, is often accompanied by urogenital defects in calves. This paper reports a case of atresia ani with diphallus and separate scrota in a calf. The calf was born with atresia ani; surgery (to open the anus) was performed 3 days after birth. No urogenital abnormalities were noticed until 4 months after birth. At that time, two separate scrota (each containing a testis) and a sac-like structure in the middle of two scrota, were visible. The gait was abnormal, with abduction of the hind limbs while walking. Additionally, the hind legs appeared wider than usual at the hip joints. Two weeks later, two peni (diphallia) was observed, each in a separate preputial sheath. The calf had a normal karyotype on cytogenetic examination. Plasma concentrations of testosterone at 5.5, 6, and 7 months of age were 3.5, 1.9, and 1.7 ng/ml, respectively. At necropsy (7 months of age), the prepuce was thick and the glans of the right penis was adhered to the prepuce. The left penis did not have a urethra or retractor penis muscles. The sac-like structure in the middle of the two scrota contained the urinary bladder and a loop of small intestine. The pubic bone had failed to fuse at the pelvic symphysis. In conclusion, this is the first reported case of atresia ani with diphallus, separate scrota, and pubic bone separation in a calf.

Flap technology for reconstructions of urogenital organs.

The purpose of this review is to summarize the different reconstructive options for urogenital indications. The development of various flap techniques to restore congenital and acquired urogenital defects is presented. Various reconstructive techniques have been demonstrated recently. On the basis of the reconstructive requirements, two main techniques can be defined: the standard local or regional flap technique (pedicled flap) and the more sophisticated microvascular free flap technique. Free tissue transplantation (transfer) is a procedure that involves microvascular transplantation of a flap (a fasciocutaneous, muscle or composite flap) in one stage from a donor site in the body to a distant recipient site. The viability of the transplanted flap is maintained by microvascular anastomosis between the flap's vessels (at least one artery and one vein) and recipient vessels. Re-innervation and functioning muscle contraction is achieved by suturing the vessels and a motor nerve in the recipient area to a motor nerve of a free transplanted muscle. After regeneration of the nerve and re-innervation of the transplanted muscle, a functioning free transplanted muscle offers enough contractile capacity and strength to replace the function of the missing muscles at the recipient site. The technique of microvascular free tissue transfer necessitates extensive experience in microvascular technique and this approach could be efficiently applied in cooperation with other specialists. Recent studies show the development and clinical application of these new surgical techniques in urology (e.g. in the treatment of bladder acontractility using innervated free latissimus dorsi muscle and in the use of a free microvascular fillet lower leg flap for the reconstruction of a large pelvic-floor defect). Various reconstructive requirements define the techniques for reconstruction. The main principle is to obtain optimal anatomical and functional reconstruction with minimal donor site morbidity. Depending on the etiology of the defect, different reconstructive options are available to optimize the reconstructive result. Optimal reconstruction might best be achieved by adopting an interdisciplinary approach in which the primary objective is to provide the best possible outcome for each patient. This review presents the main indications for and principles of flap selection according to the reconstructive requirements.