5/15/2017 Hypospadias

HYPOSPADIAS
PediatricUrology|Authors(/core_topic.cfm?coreid=114&page=authors)

1.Definition
Hypospadiasisacongenitaldefectcharacterizedbyaurethralmeatusproximaltothemidglansontheventralaspectofthe
penis.Inthemajorityofcases,thereisanabsenceofforeskinontheventralaspectoftheglans.Chordee,ventralcurvatureof
thepenis,generallyoccurswithhypospadiasanditsseveritygenerallycorrelateswiththedegreeoftheurethraldefect.

2.RiskFactorsandPathophysiology
Thepenis(andclitoris)derivesfromthegenitaltubercle,whichisventrallycurved.Themaleurethraformsbyfusionofthe
genitalfoldsundertheinfluenceofandrogens,between814weeksgestation.Testosteroneissynthesizedbythefetaltestes
(Leydigcells).Inadults,pituitarygonadotropinsstimulatetestosteronesynthesis.Incontrast,fetaltestosteronesecretionis
undertheinfluenceofplacentalhCGduringthefirst14weeksofgestation.Testosteroneisconvertedtothemorepotent
androgen,Dihydrotestosterone(DHT),bytheenzyme,5alphareductase,intheexternalgenitalia.1(#ref_2263)Thependulous
maleurethraisaderivativeoftheurogenitalsinus(UGS)andhaspseudostratifiedandstratifiedcolumnarepitheliuminthe
penileportionandanonkeratinizing,stratifiedsquamousepitheliumliningtheglanularportion.Therearetwoproposed
mechanismsofglansurethraldevelopment:ectodermalingrowthcannulatingtheglans2(#ref_2264)versusUGStabularizationto
thetipoftheglans.3(#ref_2265)Similartotheurethra,theprepuceisinitiallyopenandfusesventrallyaftertheurethraforms.
Hypospadiasisinmostcasesduetoarresteddevelopmentwithfailureofventralurethralandpreputialfusionandadegreeof
corporalventralcurvature.

Thenormaldevelopmentofthemaleurethrarequiresappropriatematernalandfetalhormonelevelsduringacriticalwindowof
morphogenesis.Anumberoffactorscaninfluencethisdelicateinteractionofhormones,receptorsandtissues.Maternal
nutrition,parity,age,twinning,placentalhealth,paternalfertilityandpossiblyseasonsmayinfluencethehormonal
milieuand/ortheprocessofurethralmasculinization.Subtledefectsinquantityand/ortimingofandrogensynthesisbythe
fetaltestiscouldbecritical.Evaluationoftestisandpituitaryfunctionafterbirthmayormaynotreflectthesame
deficiency.Androgenreceptor(AR)mutationsanddefectsinfunction,levelsorbindinghavebeenfoundinpatientswith
severehypospadias.ARmutationsarerareinpatientswithisolatedhypospadias.4(#ref_2266)Fetalexposureto
xenoestrogensandxenoandrogenscouldaugmentachild'sinherentpredispositiontohypospadiasandexplainthe
increasingincidenceofthedisorder.5(#ref_2267)Forthemajorityofchildrenwithhypospadias,thecauseislikelymultifactorial.6
(#ref_2268)

3.Epidemiology
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Hypospadiashashistoricallyhadanincidenceof1/1251000livemalebirths.RecentdatafromtheUnitedStateshasshown
anapparentdoublingoftherateofhypospadiasto1/125250malebirths.Theincidenceofhypospadiasinnonwhitesis
increasing.7(#ref_2269)Muchofthisdataiscomplicatedbyreportingcriteria.Thefamilialaggregationofhypospadiasiswell
recognizedwithabout20%ofpatientshavinganaffectedrelative.Whencomparedtosingletons,theprevalenceof
hypospadiasishigheramongmembersofmalemaletwinpairsandlowerinmalefemalepairs.Bothbirthweightand
gestationallengtharereducedinboyswithhypospadiascomparedtocontrols.8(#ref_2270)

4.DiagnosisandEvaluation
Hypospadiasisrarelyassociatedwithextraurogenitalanomalies,chromosomaldefectsandcongenitalmalformation
syndromes,aswellasdisordersofsexualdevelopment(DSD).Thevastmajorityofboyswithhypospadiashavenoother
healthproblemsandareconsideredtohave"isolated"hypospadias.Thephysicalexaminationwilldemonstrateabsenceofthe
ventralforeskinandaproximalmeatus.Otherattributesthatshouldbenotedincludechordee,bifidscrotumandpenoscrotal
transposition.Avariantofhypospadias,megameatusintactprepuce,demonstratesalarge,fishmouthmeatussometimes
extendingbelowthecorona.Itisusuallyfoundafterorduringneonatalcircumcisionorinanolderchildwhentheforeskin
retracts.

Bladderandkidneyimagingarenotnecessaryunlessthechildhasarelevantmalformationsyndrome.9
(#ref_2271)
Undescendedtestesareassociatedwithhypospadias.Theincidenceincreaseswithseverityofhypospadias.10
(#ref_2272),11(#ref_2273)
Theassociationmaybeduetosimilarriskfactorsofprematurityandlowbirthweight.Adisorderof
sexualdevelopment(DSD)shouldbeconsideredwhenonetestisisnonpalpableandtheotherisinguinalorbothtestesare
nonpalpable,inwhichcaseakaryotypeshouldbeconsidered.

5.Treatment
Thegoalofhypospadiasrepairistocreateastraightpeniswithanorthotopicallyplaced,slitlikemeatus,allowingthepatientto
voidinthestandingposition.Awidevarietyofsurgicalapproacheshavebeendescribedforthecorrectionofhypospadias.12
(#ref_2274),13(#ref_2275),14(#ref_2276)Managementstrategiesdependonthelocationofthemeatus,qualityoftheurethralplate

andspongiosum,sizeoftheglans,degreeofventralcurvature,andquantityandqualityofskin.Whiledistal
hypospadiasmaynotimpactvoiding,sexualfunctionorfertility,manyparentswillelecttocorrecthypospadiastoimprovethe
cosmeticappearance.Moreseverehypospadiasandchordeecancompromiseachild'sabilitytovoidstandingup,deliver
spermandhavesexualintercourse.

5.1TimingofSurgery
Considerationofsurgicaltiminginchildrenisduetopsychosocialaspectsrelatedtoseparationanxietyfromparents,
interventionpriortowalkingandpottytraining,aswellasdecreasedrecollectionofthesurgery.Ifatwostagesurgeryis
required,thefirstinterventionshouldbeperformedatanagethatisyoungenoughtoallowthesecondstageprocedure,
typicallydelayedby69months,tobecompletedpriortoanagerelevanttothesameconcernslistedabove.

Manyauthorsreferencethe1996ActionCommitteefortheAmericanAcademyofPediatricsSectionofUrology,which
recommendedsurgerybetween612monthsbasedonanestheticrisks,psychosocialfactorsandtechnicalaspectsofthe
repair.15(#ref_2277)WhileKorvaldetal.observedalowercomplicationrateinsurgeriesperformedat1yearoldversus5years
old,16(#ref_2278)Weberetal.didnotobserveadifferenceinoutcomeswhencomparingsurgeriesperformedbefore18months
versusafter18months.17(#ref_2279)Manzonietal.recommendavoidingsurgerybetween18monthsandthreeyearsoldasthis
istheonsetofgenitalawarenessandrepresentsaphaseofdifficultanduncooperativebehaviorinthechild'sdevelopment.18

(#ref_2280)
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(#ref_2280)Garnieretal.havealsoobservedanincreasedcomplicationratewithincreasingage,notingageabove2y.o.asa

significantpredictorofcomplications,whentheyextendedtheanalysisbeyondcomplicationsrequiringinterventiontoinclude
healingproblems,infections,lowerurinarytractsymptomsanddysfunctionalvoiding.19(#ref_4554)

5.2GlansSize
Asmallglanswidthhasbeenproposedtobeanindependentriskfactorforcomplicationsafterhypospadiasrepair.Bushetal.
havemeasuredglanssizeintheirseriesofhypospadiasrepairandreportanincreasedcomplicationrateinglanswidth<14
mm.20(#ref_4553)However,otherauthors,Faaseetal.,havealsoprospectivelyrecordedglanssizeanddidnotobservean
increasedcomplicationrateassociatedwithglanssize.21(#ref_4552)

5.3PreOperativeHormonalStimulation
KoffandJayanthireportedthattheuseofpreoperativehumanchorionicgonadotropin(hCG)ledtosimplerrepairsdueto
increasedpenilesizeandlength,decreasedhypospadiasseverityinregardstomeatalpositionandassociatedcurvature,as
wellasincreasedvascularityandthicknessofproximalcorpusspongiosum.22(#ref_2281)Aglansthatissmallmayincrease
tensionontheglansclosure,increasingrisksofglansdehiscenceand/orfistulaformation.However,theuseofpreoperative
hormonetherapyremainscontroversial.

Somesurgeonsreservehormonesforseverehypospadias,microphallusorsmallglanssize.Although,hCG,testosteroneor
dihydrotestosteronecanbeused,variabilityexistsinformulations,routeoftherapy(parenteralvs.transdermal),timingof
therapy,anddurationoftherapy(Table1(#table_1)).9(#ref_2271)Penilegrowthisenhancedirrespectiveofadministration
route.Complicationratesweresignificantlyloweredinaprospectiverandomizedtrialforpatientswithdistalhypospadias.23
(#ref_2282)However,preoperativehormoneuseismorecommonplaceinproximalrepairs.Onerecentstudysuggested

thathormonestimulationmightinterferewithwoundhealing,asdemonstratedbyanincreasedcomplicationrate.24(#ref_2283)

Open/CloseTable(javascript:openTable(1))
Table1:Preoperativehormonestimulationanditseffectonpenilesize(javascript:openTable(1))

Mean
Increase Mean
in Increasein
penis glanular
Routeof length % circumference %
Study n Hormone Administration Dosage Protocol (mm) increase (mm) increase

Sakakibara 15 Testosterone Topicalcream NR Dailyfor NR NR NR NR

etal. 3weeks
(1991)25
(#ref_2305)

Koffand 12 Human Parenteral 250IU(<1 Twice 133 77 NR NR

Jayanthi chorionic year) weekly
(1999)22 gonadotropin 500IU(15 for5
(#ref_2281) years) weeks
starting
68
weeks
before
surgery
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Table1:Preoperativehormonestimulationanditseffectonpenilesize(javascript:openTable(1))

Mean
Increase Mean
in Increasein
penis glanular
Routeof length % circumference %
Study n Hormone Administration Dosage Protocol (mm) increase (mm) increase

Luoetal. 25 Testosterone Parenteral 25mg Monthly 40 20 104 38

(2003)26 enanthate for3
(#ref_2306) months
before
surgery

Ishiietal. 17 Testosterone Parenteral 25mg Monthly 101 NR NR NR

(2010)27 enanthate upto3
(#ref_2307) times

Chalapathi 13 Testosterone Topical NR Twicea 118 59 NR NR

etal. enanthateoil dayfor3
(2003)28 weeks
(#ref_2308) before
surgery

Chalapathi 13 Testosterone Parenteral 2mg/kg Weekly 126 68 NR NR

etal. enanthate for3
(2003)28 weeks
(#ref_2308) before
surgery

Nerlietal. 10 Testosterone TopicalCream Manufactured Dailyfor 38 18 100 36

(2009)29 sachets 3weeks
(#ref_2309)

Nerlietal. 11 Testosterone Parenteral 2mg/kg Monthly 38 18 102 37

(2009)29 enanthate for3
(#ref_2309) months
before
surgery

Gorduzaet 21 Human Parenteral 1,500IU 6doses NR NR NR NR

al.(2010) 24 chorionic every
(#ref_2283) gonadotropin other

Gorduzaet 25 Testosterone Parenteral 100mg/m2 26 NR NR NR NR

al.(2010)24 enanthate monthly
(#ref_2283) injection

Abbreviation:
NRnotreported.

TablereprintedwithpermissionfromNatureReviews:Urology
Downloadtableasimage.(core/img/114_table1.png)
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5.4SurgicalTechnique
Giventhevariabilityofglanssize,locationofmeatus,penilesizeanddegreeofcurvature,noonetechniqueisappropriatefor
allrepairs.Ingeneral,thesurgeryentailsfivesteps:orthoplasty(penile
straightening),urethroplasty,meatoplastywithglanuloplasty,scrotoplastyandskincoverage.12(#ref_2274)

Historically,repairshavebeencategorizedinto(i)urethralplatetubularization,(ii)urethralplateaugmentation(perimeatal
ordorsallybasedskinflaps),and(iii)urethralplateexcisionandreplacementwithskinorbuccaltube(oneortwostage).
Veryfewstudieshavesystematicallycomparedoutcomesforthedifferentrepairs.30(#ref_2284),31(#ref_2285),32(#ref_2286)Surgical
decisionmakingoftenwilldependupondegreeofventralcurvatureandhealthoftheurethralplate.33(#ref_2287)

5.5VentralCurvature
75%ofpatientswithpenilecurvaturecanbecorrectedwithdeglovingoftheventralskintothepenoscrotaljunction.After
degloving,curvaturecanbeassessedwithaproximaltourniquetandinjectionofsalineorvasoactivedrugsintothecorporal
body.Iftheerectpeniscanbestraightenedwithgentlepressurewithafinger,dorsal,midlinepermanentplicationsutureswill
besufficienttocorrectthecurvature.34(#ref_2288)Smallventralreleasingincisions(fairycuts)maybesufficientorusedto
augmentthedorsalplication.Aggressiveuseofdorsalplicationsuturesmayleadtopenileshortening.

Forcurvaturegreaterthan30degrees,someauthorsadvocatemobilizingtheurethralplate.35(#ref_2289),36
(#ref_2290)Alternatively,severecurvaturemaybecorrectedwithdivisionandproximalmobilizationoftheurethralplate.Severe

curvaturemayrepresentadisproportionbetweenthedorsalandventralaspectsofthecorporacavernosa.Thiscanthusbe
correctedwithaventrallengtheningprocedure,transverselyincisingtheventraltunicaalbugineaatthepointofthegreatest
curve.Thedefectisthenpatchedusingadermalgraft,atunicavaginalisflaporcommerciallyavailablesmallintestine
submucosa.

5.6Urethroplasty
Onegoalofhypospadiasrepairistoadvancethemeatustotheorthotopiclocationontheglans.Fordistal(glanularor
coronal)hypospadias,suchcorrectionmaybeachievedwithmeataladvancementproceduresincludingthe
urethromeatoplasty,meataladvancementandglansplasty(MAGPI),Mathieuorflipflap,andmeatalinvertedVglansplasty.12
(#ref_2274)

Midshaftanddistalhypospadiasmaybeapproachedwithatubularizationoftheurethralplate,theThierschDuplayrepair.
Developednearly140yearsago,itisthebasisofmanysurgicalapproachesincludingthecurrentlypopularTIPprocedurein
whichincisingtheurethralplateallowsittobehingedforurethraltabularization.Narrowurethralplatesthatpreviouslywerenot
adequateforaThierschDuplayrepaircouldnowbeutilizedintheTIPapproach.37(#ref_2291)

Alternatively,thepreputialonlayislandflapcanbeusedtoaugmenttheurethralplate.12(#ref_2274),14(#ref_2276)Inthisapproach,
aninnerpreputialflap,basedonavascularpediclefromthedorsalskin,istransferredventrallyandsewntotheurethralplate,
tubulariztiontheneourethra.38(#ref_2292)Forsevereventralcurvature,theurethralplatemaybecompletelyresectedanda
transverseislandtuberepairperformedtorecreatetheurethra.Similartotheonlayflap,innerpreputialskinonadorsal
vascularizedpedicleisrolledintoaneourethra.Thisrepaircarrieshigherrisksofurethraldiverticulumandsomesurgeons
favoratwostageapproach12(#ref_2274),38(#ref_2292)inwhichtheurethralplateisexcisedintheprocessofcorrectingventral
curvature.Dorsalskinistransferredventrallywhichissubsequentlytubularizedtocreatetheneourethrainasecondsurgery.

Buccalmucosahasbecomeapopulargraftusedinurethralreconstruction.Whilecommonlyusedinfailedrepairs,itisalso
nowutilizedinprimaryrepairsand2stagerepairs.14(#ref_2276),39(#ref_2293)Afterpenilestraighteningandresectionofscarred
urethra,buccalmucosa,harvestedfrominnercheekorlip,isgraftedtotheventralbed.Asecondsurgeryisperformedfor

14(#ref_2276)
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tubularizationandskincoverage.14(#ref_2276)Severalapproacheshavenowincorporatedbuccalgraftinginonestagerepairs
forproximal,perinealandscrotalhypospadias.40(#ref_2294)

5.7UrethroplastyCoverage
Asecondlayerofwellvascularizedtissueisoftenemployedtocovertheurethroplastyinhopesofdecreasingpostoperative
complications.Deepithelializedsubcutaneousflapscanberaisedfromthedorsalorlateralskinforcoverageoftherepaired
neourethra.13(#ref_2275)Alternatively,tunicavaginalisorscrotalflapscanbeusedasasecondlayerofcoverage.41(#ref_2295),42
(#ref_2296)Vascularizedtissuecoveragehasbeenshowntodecreaseoverallcomplicationandfistularates.37(#ref_2291),43

(#ref_2297),44(#ref_2298),45(#ref_2299)

5.8Complications
Commonpostsurgicalcomplicationsincludemeatalstenosis,urethrocutaneousfistula,diverticulum,urethralstricture,
dehiscence,persistentventralcurvature,proximalpositionofurethralmeatusandpoorcosmeticoutcome(Table2
(#table_2)).45(#ref_2299)Whilepostoperativeurinarydrainagehasbeenshowntoinfluencecomplicationrates,thetypeand
durationofurinarydiversion,cathetersize,dressingtype,andanestheticchoicedonotappeartosignificantlyinfluence
outcomes.45(#ref_2299)ReoperativesurgeryalsoisknowntoincreasecomplicationsratesandSnodgrassandBushreporta
twofoldriskforsubsequentcomplicationsoverprimaryrepair,increasingto40%withthreeormoreoperations.46(#ref_4551)
Theysupportpriortheoriesthatsuccessivesurgeriescancompromisevascularityofpeniletissues.

Notsurprisingly,complicationratesrisewithdegreeofhypospadias,from5%fordistalto70%forproximalrepairs.
Usingahospitalconsortiumdatabase,LeeandKurzrockobserveda9%secondarysurgeryratefordistalhypospadias
repairs.47(#ref_2300)Inthispopulationbasedstudyofover5,000patients,increasedpatientagewasassociatedwithsecondary
endoscopicintervention,whilelowsurgeonvolumeindependentlyincreasedrisksforrepairoffistula,stricture,or
diverticulum.47(#ref_2300)Furthermore,complicationscanextendintoadulthood.WilcoxandSnodgrassreportedthatupto
40%ofmenwithahistoryofseverehypospadiaswillreportsomelevelofvoidingproblems,while20%willhavesexual
problems.48(#ref_2301)

Open/CloseTable(javascript:openTable(2))
Table2:OverviewofComplicationsinhypospadiasfailure(javascript:openTable(2))

Clinical Treatmentoptions
Complication Prevalence presentation Diagnostictools (successrate)

Recurrent 932%49 Curvedpenis Clinicalassessmentphotoserectiontest Notreatmentif<30

curvature (#ref_2310) duringerection (NR)
corporoplasty(93
96%)50(#ref_2320),51
(#ref_2322)

urethralsubstitution
(NR)

Preputial 220%52 Tightoropen Clinicalassessment Circumcision(100%)53

dehiscenceor (#ref_2311) prepuce (#ref_2323)

secondary
phimosis

Glans 08%54 Meatalregression Clinicalassessment Notreatment(NR)

dehiscence (#ref_2312) tocoronalsulcus redodistalurethroplasty
(7095%3)55
(#ref_2324),56(#ref_2325)
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Table2:OverviewofComplicationsinhypospadiasfailure(javascript:openTable(2))

Clinical Treatmentoptions
Complication Prevalence presentation Diagnostictools (successrate)

Urethralfistula 428%57 Doublestream Clinicalassessment(number,size,and Simpleclosure(75

(#ref_2314) location)calibrationofdistalurethra 100%)58(#ref_2326)
closurewithflaps(90
100%)58(#ref_2326),59
(#ref_2327)

Urethral NR Recurrent Clinicalassessment Retubularization(74

breakdown hypospadias 81%)60(#ref_2328),61
(#ref_2329)

augmentation
urethroplasty(76
85%)61(#ref_2329),62
(#ref_2330)

substitution
urethroplasty(62
66%)61(#ref_2329),63
(#ref_2331)

Meatalstenosis 014%57 Weakstream Clinicalassessmentcalibrationretrograde Meatotomy(100%)57

(#ref_2314) otherlowerurinary andvoidingurethrographyandcystoscopyif (#ref_2314)meatal

tractsymptoms stricturesuspected

Urethralstricture 612%64 Weakstream Clinicalassessmentmeatalcalibration Urethraldilatation(21

(#ref_2315) otherlowerurinary retrogradeandvoidingurethrographyand 40%)64(#ref_2315)
tractsymptoms cystoscopyifstricturesuspected endoscopicincision
(NR)
augmentation
urethroplasty(53
100%)64(#ref_2315)
substitution
urethroplasty(NR)

Urethralstricture 416%65 Weakstream Clinicalassessmentmeatalcalibration Substitution

owingtoBXO* (#ref_2316),66 otherlowerurinary retrogradeandvoidingurethrographyand urethroplastywithoral
(#ref_2317) tractsymptoms cystoscopyifstricturesuspected mucosagraft(NR)

Urethral 412%67 Urethralballooning Clinicalassessmentcalibrationofdistal Urethraltapering

diverticulum (#ref_2318) duringmicturition urethraretrogradeandvoidingurethrography (100%)67(#ref_2318)

Hairyurethra 515%68 Recurrenturinary Urethroscopy Ablationofhairsand

(#ref_2319) infectionsand theirfollicles(NR)
urethralstones substitution
urethroplasty(NR)

Abnormalskin 55%50 Abnormal Clinicalassessment Skinreconfiguration

configuration (#ref_2320) appearance (NR)

Skindeficiency 5%69 Trappedpenis Clinicalassessment Freeskingrafts(NR)

(#ref_2321) skinexpanders(NR)
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Table2:OverviewofComplicationsinhypospadiasfailure(javascript:openTable(2))

Clinical Treatmentoptions
Complication Prevalence presentation Diagnostictools (successrate)

*Afterrepairincorporatingapreputialskinflap.
Onlyaftertuberepair.

Abbreviations:
BXObalanitisxeroticaobliterans
NRnotreported.

TablereprintedwithpermissionfromNatureReviews:Urology

Downloadtableasimage.(core/img/114_table2.png)

6.Costs
Whilethecostsofhypospadiasrepairhavedecreasedwiththetransitionfrominpatienttooutpatientsurgery,fewstudieshave
formallyassessedthefinancialburdenofhypospadiasmanagement.70(#ref_2302),71(#ref_2303),72(#ref_2304)Pohlsetal.estimated
that$8millionwasincurredinnationalinpatientexpendituresin2000,withtheaveragecostofhospitalizationexceeding
$5,389perpatient.70(#ref_2302)Theoverallhealthcarecostsforthetreatmentofhypospadiasarecertainlymorewhen
consideringthenumberofpatientsaffected,increasingincidenceandmanagementoflongtermcomplications.Someofthis
mightbemitigatedbyincreasedspecialization.

7.ClinicalCarePathway
(SeeFigure1(#fig_1))

Patientsshouldbethoroughlyexaminedwithhistoryandphysicalexam.NonpalpabletesticlesandotherconcernsforaDSD
shouldpromptkaryotypeandhormonalevaluation.Glans/penissize,severityofhypospadiasandskinquantitywill
determinetheuseofhormonestimulation,timingofsurgeryandsurgicaltechnique.Urethralstentingistypically714days,
thoughcatheteruseissurgeondependentandvariesbasedonsurgicalapproach.Similarly,antibioticprophylacticcoverageis
basedonsurgeonpreferenceandhasnotbeenevaluatedwellintheliterature.

(core/img/114_fig1.png)
Figure1
 5/15/2017 Hypospadias

References
SeminalReference AUAReference

1. WilsonJD,GriffinJE,RussellDW.Steroid5alphareductase2deficiency.Endocrinereviews199314:57793

Impairmentof5alphareductaseenzymecausesvariablephenotypicmanifestationsofdisordersofsexual
development,mostcommonlyambiguousgenitalia.Mutationsinthesteroid5alphareductase2genearethecause.

2. GlenisterTW.Theoriginandfateoftheurethralplateinman.Journalofanatomy195488:41325.

Afterexamininghistologicstainsoffetalurethrastheauthormadeseveralconclusionsincluding:theurethralplateisan
outgrowthoftheurogenitalsinus,thespongyurethraandproximalportionoftheglandarurethraarederivedfromthe
urethralplate,thedistalportionoftheglandarurethraisderivedfromthesurfaceectoderm.

3. KurzrockEA,BaskinLS,CunhaGR.Ontogenyofthemaleurethra:theoryofendodermaldifferentiation.
Differentiationresearchinbiologicaldiversity199964:11522.