The document discusses hypospadias, including its etiology, embryology, classification, and presentation. Hypospadias is caused by incomplete development of the penis during embryogenesis. It results from failed closure of the urethral groove and can range from mild forms with the urethral opening near the tip of the penis to more severe forms with the opening in the scrotum or perineum. Doctors classify hypospadias based on the location of the urethral meatus and the level of division of the corpus spongiosum to determine the appropriate surgical approach.

1. Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
HYPOSPADIAS
ETIOLOGY, EMBRYOLOGY AND CLASSIFICATION
1

2. Moderators:
Professors:
 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
 Prof. Dr.A. Senthilvel, M.S., M.Ch.,
Asst Professors:
 Dr. J. Sivabalan, M.S., M.Ch.,
 Dr. R. Bhargavi, M.S., M.Ch.,
 Dr. S. Raju, M.S., M.Ch.,
 Dr. K. Muthurathinam, M.S., M.Ch.,
 Dr. D.Tamilselvan, M.S., M.Ch.,
 Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai.
2

3. Introduction
 Hypospadias can be defined as incomplete virilization of the
genital tubercle that causes an insufficient development of the
tissues forming the ventral aspect of the penis.
 The urethral meatus may be proximal to its normal glanular
position anywhere along the penile shaft, scrotum, or perineum
3 Dept of Urology, GRH and KMC, Chennai.

4.  Incidence – 1:250 male births ,
higher if there is a family history – 1:80-100 male
births
 Associated anomalies
 Undescended testes – 9%
 Inguinal hernias – 9%
 Upper urinary tract anomalies 1-3%
 Cryptorchidism
4 Dept of Urology, GRH and KMC, Chennai.

5.  Approximately 90% of hypospadias cases are isolated
penile defects
 Syndromic hypospadias is suspected with development delay,
dysmorphic facies, and/or anorectal malformation. Examples
include:
 • Smith-Lemli-Opitz syndrome
 autosomal recessive mutation of the DHCR7 gene on chromosome 11q13
coding for 7-dehydrocholesterol reductase.
 mental retardation, facial dysmorphism, microcephaly, and
syndactyly.
5 Dept of Urology, GRH and KMC, Chennai.

6.  • WAGR syndrome (Wilms tumor,aniridia, genital anomalies,mental
retardation)—results from a deletion in chromosome 11p13
 G syndrome (Opitz G/BBB syndrome)
 X-linked mutations in the midline-1 gene or autosomal dominant
deletions in chromosome 22q11
 hypertelorism, tracheoesophageal defects, cleft lip/palate, and
mild mental retardation.
6 Dept of Urology, GRH and KMC, Chennai.

7.  Wolf-Hirschhorn syndrome
 deletions in chromosome 4p resulting in mental retardation, seizures,
abnormal facies, and midline defects
 13q deletion syndrome
 mental retardation,facial dysmorphia, imperforate anus, and
hypospadias with penoscrotal transposition
 Hand-foot-uterus syndrome
 autosomal dominant condition caused by mutations in the HOXA13 gene
on chromosome 7p14-15,resulting in bilateral thumb and great toe
hypoplasia.
7 Dept of Urology, GRH and KMC, Chennai.

8. ANATOMY OF HYPOSPADIAS
 Three associated anomalies are classically found in the
hypospadiac penis:
 (1) an ectopic opening of the urethral meatus located at any
place between the glans and the base of the penis,
 (2) a ventral curvature of the penis (chordee), and
 (3) a hooded foreskin with a marked excess of skin on the
dorsum of the penis and a lack of skin on the ventrum.
8 Dept of Urology, GRH and KMC, Chennai.

9.  The chordee and the hooded foreskin are not constant, and a
hypospadiac meatus may be found under a normally formed
prepuce.
 Chordee may occur in isolation, without an ectopic urethral
opening, but it is often associated with a hypoplasia of the
corpus spongiosum.
9 Dept of Urology, GRH and KMC, Chennai.

10.  Anatomically, the characteristics of the hypospadias, from the tip
to the base of the ventral aspect of the penis
 1.The glans opens ventrally
 2.A segment of urethral tube of variable length is missing and is
replaced by a urethral plate extending from the ectopic meatus up
to the glans cap, between the two corpora cavernosa
 3.There is a hypoplastic length of the tubular urethra that is not
surrounded by any corpus spongiosum; often, it is covered by a thin
layer of skin stuck tightly on it.
10 Dept of Urology, GRH and KMC, Chennai.

11.  4.The division of the corpus spongiosum is always proximal to the ectopic
meatus in two pillars that extend laterally up to the glans cap in a fan-
shaped position;
this division of the corpus spongiosum is often outlined on the ventral skin
by a small cutaneous ridge
11 Dept of Urology, GRH and KMC, Chennai.

12.  5. Proximal to the division of the corpus spongiosum, all of the
structures forming the ventral aspect of the penis are normal
 6.The frenular artery is consistently missing
 7.The dorsum of the penis is normal
12 Dept of Urology, GRH and KMC, Chennai.

13.  The division of the corpus spongiosum marks the proximal
landmark of the malformation.
 The preputial hood is the direct consequence of the ventral
triangular defect.
 The summit of the triangle is the division of the corpus
spongiosum, the two sides are represented by the two lateral
pillars of spongiosum, and the glans plate is its base
13 Dept of Urology, GRH and KMC, Chennai.

14.  At the time of surgery,it is easy to
delineate this triangle by drawing
two lines along the
cutaneomucosal junction of the
prepuce on each side, Where the
two lines cross is the point where
the corpus spongiosum splits.
14 Dept of Urology, GRH and KMC, Chennai.

15.  The chordee itself is a direct consequence of the abnormal
proximal division of the corpus spongiosum and the subsequent
hypoplasia of the ventral tissues sitting in the triangular defect.
 Chordee is related to
 (1) the tethering of the ventral hypoplastic skin onto the underlying
structures (urethra) in most cases;
 (2) the fan-shaped lateral and upward extension of the divided corpus
spongiosum;
 (3) the tethering of the urethral plate and the hypoplastic distal urethra
(not surrounded by any spongiosum) onto the corporeal surface; and
 (4) in rare cases, an asymmetric development of the corpora cavernosa
15 Dept of Urology, GRH and KMC, Chennai.

16. Etiology
 Hypospadias results from partial or complete failure of
urethral folds to form throughout their normal length or a
failure of the folds to close distally if they have formed
 The extent of the closure determines the position of the
urethral orifice
 Hypospadias results from multiple factors
16 Dept of Urology, GRH and KMC, Chennai.

17.  The hypospadias occurs due to incomplete embryologic
development as a result of:
■ abnormal androgen production by the fetal testis
■ limited androgen sensitivity in target tissues of the developing
genitalia
■ premature cessation of androgenic stimulation due to early
atrophy of the Leydig cells of the testes.
17 Dept of Urology, GRH and KMC, Chennai.

18. Endocrine factors
 Result from an endocrinopathy in which there is a disruption in
the synthetic biopathway of androgens.
 More than just a focal malformation, hypospadias may be a local
manifestation of a systemic endocrinopathy
18 Dept of Urology, GRH and KMC, Chennai.

19.  A qualitative androgen receptor abnormality or defects at a
postreceptor level
 Mutation in the luteinizing hormone (LH) receptor in the testis
 A delay in the maturation of the hypothalamic–pituitary–testicular
axis
19 Dept of Urology, GRH and KMC, Chennai.

20. Genetic factors
 Müllerian inhibiting substance (MIS) has a role in the etiology of
hypospadias
 MIS inhibits cytochrome P450c17 CYP17, the enzyme that catalyzes the
committed step in testosterone synthesis
 MIS may directly inhibit testosterone production by suppressing the
CYP17 gene
 Abnormalities of other genes - fibroblast growth factor-10 (FGF-10)
 Mutation in SRD5A2 gene on chromosome 2 - 5α reductase II (5αRII)
defect
20 Dept of Urology, GRH and KMC, Chennai.

21. Environmental factors
 Insecticides, pharmaceuticals,and plant estrogens contain
estrogenic ingredients
 Manufacturers of cans used in the canned food industry coat the
inside of the cans with plastics known to contain estrogenic
substances.
21 Dept of Urology, GRH and KMC, Chennai.

22.  These substances are ultimately present in freshwater and seawater
in trace amounts that bioaccumulate and concentrate in higher
organisms of the food chain.
 predators at the top of the food chain, such as large fish, birds, sea
mammals, and humans, accumulate high levels of estrogenic
environmental contaminants.
 Humans and wild animals are constantly exposed to estrogenic
compounds that are known to disrupt reproduction – the so-called
endocrine disrupters.
22 Dept of Urology, GRH and KMC, Chennai.

23. 23 Dept of Urology, GRH and KMC, Chennai.

24. Embryology of hypospadias
 The genital tubercle appears during the 4th week of gestation for
development of either the clitoris or penis.
 Endodermal cells from the cloaca migrate along its ventral
midline surface to create the urethral plate, while proliferating
mesenchyme on either side establishes the urogenital folds
 Subsequent phallic development is dependent upon androgenic
stimulation during a critical period from the 9th to 12th weeks.
24 Dept of Urology, GRH and KMC, Chennai.

25.  5αR II in the genital tubercle catalyzes the conversion of
testosterone, produced by fetal Leydig cells within the testes, to
dihydrotestosterone (DHT).
 DHT then binds to androgen receptors to initiate a cascade of
downstream effects.
 Androgen stimulation causes the genital tubercle to elongate and
the urogenital (urethral) folds to migrate toward the midline and
fuse, enclosing the urethral groove
25 Dept of Urology, GRH and KMC, Chennai.

26.  This process moves proximal to distal creating the pendulous urethra.
 Some clinicians have disputed the current theories of the formation of
the glanular urethra.
 One theory says that ectoderm from the glans surface migrates inward
to contact the distal urethral plate and establish continuity with the
urethra.
 Alternatively, the endodermal plate may continue to canalize distally
until surface ectoderm is reached.
26 Dept of Urology, GRH and KMC, Chennai.

27.  As the plate tubularizes, mesoderm within the urethral folds
differentiates into corpus spongiosum, which fuses with the glans
distally.
 Mesoderm also forms the corpora cavernosa.
 Development of the penis apparently proceeds at different rates along
the ventral vs dorsal surfaces, resulting in temporary ventral
curvature.
 the dorsal prepuce extends beyond the glans before the ventral aspect,
which follows closure of the urethral groove.
 Midline fusion of the ventral prepuce ends in the frenulum.
27 Dept of Urology, GRH and KMC, Chennai.

28. The external genitalia derive from a pair of labioscrotal swellings, a pair of
urogenital folds, and an anterior genital tubercle.
Male and female genitalia are morphologically indistinguishable until the
seventh week
28 Dept of Urology, GRH and KMC, Chennai.

29. In males the urogenital folds fuse and the genital tubercle elongates to
form the penile shaft and glans.
A small region of the distal urethra in the glans is formed by the
invagination of surface epithelial tag. The fused labioscrotal folds give rise
to the scrotum.
29 Dept of Urology, GRH and KMC, Chennai.

30. The epithelial tag and fusing urethral folds in the developing male
external genitalia
30 Dept of Urology, GRH and KMC, Chennai.

31.  Hypospadias is the result of arrested penile development.
 the urethral opening can occur from the perineum, where urethral fold
fusion begins, to the glans.
 The urethral plate extends from the hypospadiac meatus to the tip of
the glans.
 This plate is the residuum of tissues that in the normal case would have
completed urethral tubularization.
 The glans does not fuse ventrally under the meatus, resulting in two
‘wings’ on either side of the urethral plate.
31 Dept of Urology, GRH and KMC, Chennai.

32. Presentation
 The abnormal prepuce and ventral glans tilt of the newborn
penis usually signifies the presence of hypospadias.
 proximally displaced urethral orifice that is often stenotic in
appearance, but almost never obstructive.
 An exception is the megameatus variant of hypospadias.
32 Dept of Urology, GRH and KMC, Chennai.

33.  In this unusual case (6% of all distal hypospadias presentations),an
intact prepuce is present.
 The diagnosis is usually not made until after a routine neonatal
circumcision is completed
33 Dept of Urology, GRH and KMC, Chennai.

34.  The location of the meatus and extent of ventral curvature, or
chordee, should be determined.
 In some instances, multiple pinpoint dimples may be present
on the surface of the urethral plate in addition to the
hypospadiac urethral meatus.
 The meatus is always the most proximal of these defects and
physical examination or passage of a probe can confirm this.
34 Dept of Urology, GRH and KMC, Chennai.

35.  The meatus is located on the glans or distal shaft of the penis
in approximately 70–80% of all boys with hypospadias;
 20–30% of boys with hypospadias have the meatus located in
the middle of the shaft of the penis.
 The remainder of the boys with hypospadias have more
severe defects, with the urethral meatus located in the
scrotum or even more proximally on the perineum
35 Dept of Urology, GRH and KMC, Chennai.

36. CLASSIFICATION
 Surgeons classify meatal position as anterior (distal), middle,
and posterior (proximal), with more anatomically specific
subgroups being further applied
36 Dept of Urology, GRH and KMC, Chennai.

37. Classification of hypospadias based on anatomic location of the urethral
meatus. Anterior, or distal, hypospadias is the most commonly
encountered variant.
37 Dept of Urology, GRH and KMC, Chennai.

38.  The classification based on the level of division of the corpus
spongiosum is of practical help when deciding which surgical
procedure to use
38 Dept of Urology, GRH and KMC, Chennai.

39.  1. Glanular hypospadias
 The ectopic meatus sits on the glans tissue
behind the normal site.
 Although these cases may look quite minor,
they can be associated with a marked
hypoplasia of the distal urethra and a glans
tilt or chordee.
 These hypospadias cases are often tricky to
repair, because parents’ expectations are
high and surgical techniques are not
entirely satisfactory.
 The meatus may look very tight but is
rarely causing any urine flow obstruction.
39 Dept of Urology, GRH and KMC, Chennai.

40.  2. Hypospadias with a distal division of the corpus
spongiosum associated with little or no chordee
40 Dept of Urology, GRH and KMC, Chennai.

41.  3. Hypospadias with a proximal
division of the corpus spongiosum
associated with chordee .
Paradoxically, these cases are often
simpler to handle because surgical
techniques to correct the chordee
and reconstruct a long length of
urethra are well established.
41 Dept of Urology, GRH and KMC, Chennai.

42.  4. Hypospadias cripples
These are patients who have already undergone several
procedures that failed, leaving them with scarred tissues, an
abnormal meatus, strictures, urethral dehiscence, fistulas, and
bad cosmetic and psychological results.
42 Dept of Urology, GRH and KMC, Chennai.

43. THANK YOU
43 Dept of Urology, GRH and KMC, Chennai.

44. 44 Dept of Urology, GRH and KMC, Chennai.

45.  The early development of the external genitalia is similar in both
sexes.
 Migrating mesenchymal cells spread themselves around the cloacal
membrane and pile up to form swellings.
 Early in the fifth week, a pair of swellings called cloacal folds develops
on either side of the cloacal membrane.
 These folds meet just anterior to the cloacal membrane to form a
midline swelling called the genital tubercle
 During the cloacal division into the anterior urogenital sinus and the
posterior anorectal canal, the portion of the cloacal folds flanking the
opening of the urogenital sinus becomes the urogenital folds and the
portion flanking the opening of the anorectal canal becomes the anal
folds.
 A new pair of swellings,called the labioscrotal folds,appears on either side of
the urogenital folds.
45 Dept of Urology, GRH and KMC, Chennai.

46.  The most popular hypothesis of external genital and urethral
development is based on work performed in the early part of the 20th
century.
 Most embryology texts today quote the mechanism of urethral
development proposed by Glenister (1954).
 As the genital tubercle elongates in males, a groove appears on its
ventral aspect (called the urethral groove) during the sixth week.
 In both sexes an ectodermal epithelial tag is present at the tip of the genital
tubercle.
 The urethral groove is defined laterally by urethral folds, which are
continuations of the previous urogenital folds surrounding the
urogenital membrane.
 Initially, the urethral groove extends only part of the way distally
along the shaft of the elongating genital tubercle.
46 Dept of Urology, GRH and KMC, Chennai.

47.  The distal portion of the urethral groove terminates in a solid
epithelial plate called the urethral plate that extends into the glans penis.
 The solid urethral plate canalizes and thus extends the urethral groove
distally toward the glans.
 The urethral groove is thought to be lined by endoderm. Likewise, the
solid urethral plate, the distal precursor of the urethral groove,is also
believed to derive from the endodermal source.
 Clearly, fusion of the urethral folds is the key step in the
formation of penile urethra.
 A prerequisite of urethral fold fusion is the canalization of solid
urethral plate and formation of the urethral groove bounded on each
side by the urethral folds.
 If the urethral groove and urethral fold formation are abnormal, then
the urethral fold fusion is likely to be impaired as well
47 Dept of Urology, GRH and KMC, Chennai.

48.  The formation of the distal glanular urethra may occur by
a combination of two separate processes—the fusion of
urethral folds proximally and the ingrowth of ectodermal
cells distally.
 It is generally thought that the stratified squamous epithelium of th
fossa navicularis results from an ingrowth of surface ectoderm a far
proximally as the valve of Guérin.
 The lacuna magna (als known as the sinus of Guérin), which can give
symptoms of hematuri and dysuria in some boys, may form as a
result of dorsal extension of this ectodermal ingrowth.
 It was suggested recently that the entire penile urethra might
differentiate from the fusion of the endodermal urethral groove via
the mechanism of epithelial mesenchymal interactions
48 Dept of Urology, GRH and KMC, Chennai.