USS: may demonstrate ureteric dilatation and : is used to assess whether there is re \202 ux into the ectopic : may identify the ectopic ureteric ori \201 ce. : identi \201 es duplex systems and gives information on upper and ECTOPIC URETER 669 Treatment Commence prophylactic trimethoprim (2mg/kg daily) whilst conducting post-natal in vestigation. An ectopic ureter without an ureterocele, but associated with upper renal moie ty dilatation, requires urgent treatment to decompress the system and avoid the, complicati on of an infected, obstructed system (pyoureteronephrosis). Management is mainly expectant if there are no symptoms and no evi- dence of acute obstruct ion or dilatation. Where an ectopic ureter is asso- ciated with a poorly functioning renal upper pole moiety or single-system kidney, surgery is an option. This includes open or lapa roscopic upper moiety heminephrectomy or total nephrectomy with excision of the associated ureter. Ureteropyelostomy and uretero-ureterostomy can be considered in duplex systems wher e the upper renal pole has reasonable function. Where some useful function is retained in a single-system kidney, the distal ureter can be resected and re-implanted into the bladder. 1 Mackie GG, Stephens FD (1975) Duplex kidneys: a correlation of renal dysplasia with posit ion of the ureteric ori \201 ce. J Urol 114:274 \200\22380. CHAPTER 16 Pediatric urology 670 Ureterocele De \201 nition: an ureterocele is a cystic dilatation of the distal ureter as it drains in to the bladder. Incidence: 1 in 5000 \200\22312,000 clinical pediatric admissions1 (although 1 in 500 are f ound at autopsy).2 Female to male ratio is 4:1, predominantly affecting Caucasians. Ten per cent of ureteroceles are bilateral. Classi \201 cation Ureteroceles may be associated with a single or duplex renal system. Ei ghty percent are associated with the upper moiety of a duplex kidney. They are ureteroceles. Intravesical (20%): the ureterocele is completely con \201 ned with in the blad- der. These tend to be associated with single systems and are more com- mon in males. Subtypes include: - - further classi \201 ed into intravesical or extravesical Stenotic Non-obstructed when \201 lled by peristalsis of urine. : small, stenotic ureteric ori \201 ce associated with obstruction. : large ureteric ori \201 ce that tends to balloon open Extravesical (or ectopic) (80%): when the ureterocele extends to the blad- der neck or uret hra and tend to occur with duplex systems; most com- monly in females. Subtypes include: - Sphincteric ori \201 ce is wide and usually opens proximal to the external sphincter. Sphi ncterostenotic ureteric ori \201 ce is stenosed. Cecoureterocele : ureterocele prolapses p osterior to the urethra and anterior to the vagina, but the ori \201 ce is within the blad der (affects girls only). Can cause urethral obstruction. Blind ectopic : ureterocele extends into bladder neck and urethra. The : similar to sphincteric ureterocele, but the : similar to sphincteric, but no ureteric ori \201 ce. Presentation: most present with antenatal hydronephrosis. Later pres- entation in infants m ay be with symptoms of UTI, an abdominal mass, or pain. Association with ureteric duplicati on increases the risk of re \202 ux and re \202 ux nephropathy. Extravesical ureteroceles can also cause BOO and bilateral hydroureteronephrosis (urological emergency) or ureteric obstruction and unilateral hydroureteronephrosis, which require urgent assessment and inter vention. A prolapsing ureterocele can present as a vaginal mass in girls. Investigation - USS renal tract: shows a thin-walled cyst in the bladder often associated with a duplex sys tem and ectopic (dilated) ureter. If there are concerns about obstruction, USS should be pe rformed immediately after birth with a view to urgent surgical treatment. MCUG (re \202 ux into the lower moiety of an associated duplex kidney is seen in 50%). This should be perfo rmed early in the post-natal period if there is evidence of BOO, otherwise defer 3 \200\223 6 months. : can identify ureterocele location, size, and associated VUR URETEROCELE 671 MAG3 DMSA demonstrate renal cortical abnormalities in the presence of re \202 ux. : can be used for diagnosis and endoscopic treatment. Cystoscopy renogram: is used to exclude obstruction. renogram: is used to assess renal moiety function and Treatment Commence prophylactic antibiotics at birth (trimethoprim 2mg/kg daily). Urgent su rgical intervention is required for obstruction. - : emergency treatment for infected Endoscopic incision/puncture or obstructed ureteroceles. Puncture is also indicated for elective management of intravesical ureteroceles with norma l renal function. Rarely, these may require further surgery, including ureterocele excision and ureteric re-implantation to preserve renal function and prevent re \202 ux. Uretero-u reterostomy or uretero-pyelostomy (from upper to lower pole moiety): option for ectopic ure teroceles associated with a duplex system, with good function in the upper moiety and no re \202 ux in the lower moiety. Upper pole heminephrectomy : option for ectopic ureterocele associated with a duplex system with poor function in the upper moiety and no re \202 ux i n the lower moiety. Upper pole heminephrectomy, ureterocele excision, and ureteric re-impla ntation: option for ectopic ureterocele associated with a duplex system with poor function in the upper moiety and re \202 ux in the lower moiety. Nephroureterectomy with poor funct ion in both renal moieties or for poor renal function in single system. : indicated for signi \201 cant lower moiety re \202 ux 1 Malek RS, Kelalis PP, Burke EC, et al. (1972) Simple and ectopic ureterocele in infants a nd child- hood. Surg Gynaecol Obst 134:611 \200\2236. 2 Uson AC, Lattimer JK, Melicow MM (1961) Ureteroceles in infants and children: a report ba sed on 44 cases. Pediatrics 27:971 \200\2237. CHAPTER 16 Pediatric urology 672 Pelviureteric junction (PUJ) obstruction De \201 nition: a blockage of the ureter at the j unction with the renal pelvis, resulting in a restriction of urine \202 ow.* Epidemiology: childhood incidence is estimated at 1 in 1000. Boys are affected more than gi rls (ratio 2:1 in newborns). The left side is more often affected than the right side (rati o 2:1). They are bilateral in 10 \200\22340%. Etiology In children, most PUJ obstruction is congenital. Intrinsic obstruction may be due to aberrant development of ureteric/renal pelvis muscle, aberrant insertion of the ureter i nto the renal pelvis, abnormal collagen, or ureteric folds or polyps. Extrinsic causes incl ude compression of the PUJ by aber- rant crossing vessels. Coexisting VUR is found in up to 25%. Presentation PUJ obstruction is the most common cause of hydronephrosis (without ureteric d ilatation) found on antenatal USS. Infants may also present with an abdominal mass, UTI, an d haematuria. Older children present with \202 ank or abdominal pain (exacerbated by diur esis), UTI, nausea and vomit- ing, and haematuria following minor trauma. Investigation If prenatal USS has shown a large or bilateral hydronephrosis, a follow-up re nal tract USS should be performed soon after birth. If there is a prenatal unilateral hydro nephrosis (and the bladder is normal), the scan is deferred until day 3 \200\2237 (to allow normal physiological diuresis to occur, which may spontaneously improve or resolve the hyd ronephrosis). MAG3 renogram is performed at 6 \200\22312 weeks for diagnosis and to assess split renal func- tion. Signi \201 cant obstruction is unlikely if the anteroposterior ren al pelvis diameter is <15mm. Treatment Conservative: infants are placed on prophylactic trimethoprim (2mg/kg daily) unti l the diagnosis is established. Children may be observed with USS and MAG3 renogram if they remain stable, with good renal function and no other complications (such as infection or s tones). Surgery: pyeloplasty is indicated if children are symptomatic, have a signi \201 - cant hydronephrosis (>30mm AP renal pelvis diameter) or impaired split renal function (<40 %).Techniques include open or laparoscopic Anderson \200\223 Hynes dismembered pyeloplasty. Success rates are around 90 \200\22395%. Post- operative follow-up is with USS (9 MAG3 ren ogram). Where renal function is poor (<10 \200\22315%) on the side of the PUJ obstruction, options include temporary percutaneous drainage or ureteric stent to assess the poten- tial for recovery (i.e. suggesting a pyeloplasty could improve function) or nephrectomy where t he impairment is severe or irreversible. Of note, pelviureteric junction (PUJ) is also referred to as ureteropelvic junction (UPJ). This page intentionally left blank CHAPTER 16 Pediatric urology 674 Posterior urethral valves (PUV) PUV are derived from an abnormal congenital membrane arisin g from the verumontanum and attaching obliquely to the anterior urethra (beyond the externa l urethral sphincter), resulting in lower urinary tract obstruc- tion. An alternative term is COPUM or congenital obstructive posterior urethral membrane. Urethral instrumentation or spontaneous partial rup- ture of the membrane is thought to cause the classical appearance of two valve-like folds in the prostatic urethra. Incidence: 1 in >5000 males. Pathology: PUV may arise through an abnormal insertion of the Wolf \201 an ducts into the urogenital sinus during fetal development. Presentation Prenatal USS: the majority are diagnosed prenatally, with 60% identi \201 ed on USS at 20 weeks. They account for 1% of cases of antenatal hydro- nephrosis. Features in clude: bilateral hydroureteronephrosis, dilated and thick-walled bladder, dilated posterior urethra (keyhole sign), thick-walled bladder, oligohydramnios (reduced amniotic \202 uid ), and renal dysplasia. Early diagnosis is associated with poor prognosis. Newborn and infa nts: respiratory distress secondary to pulmonary hypo- plasia, palpable abdominal mass (hyd ronephrotic kidneys or distended bladder), ascites, UTI sepsis, electrolyte abnormalities ( renal impairment), failure to thrive. Older children: milder cases may present later with r ecurrent UTI, poor urinary stream, incomplete bladder emptying, poor growth and inconti- ne nce. There is a risk of renal failure, VUR, and voiding dysfunction (over- or underactive b ladder), also described as \200\230valve bladder syndrome \200\231. Associated features: \200\230pop-off valve syndrome \200\231 is seen in 20%. It describes mechanisms by which hi gh urinary tract pressure is dissipated to allow normal renal development. It includes leak ing of urine from a small blad- der or renal pelvis rupture (urinary ascites), unilateral r e \202 ux into a non- functioning kidney (VUR with renal dysplasia or VURD), and formation of bladder diverticuli. Management Commence prophylactic antibiotics immediately (trimethoprim 2mg/kg daily) and dr ain the bladder with a pediatric feeding tube or suprapubic catheter if this proves dif \201 cult. Check serum electrolyes and arrange for urgent post-natal renal tract USS and MC UG. De \201 nitive treatment is with cystoscopy and transurethral ablation of the valve. The m ost important incision is made at the 12 o \200\231clock position with either cold knife or electrocautery. Complications of surgery include urethral strictures. A temporary cutaneou s vesicostomy is indicated (com- municating stoma between the bladder dome and suprapubic a bdominal wall, allowing free drainage of urine) when the urethra is too small for the resec toscope. Alternatives are ureterostomy drainage with valve ablation performed at a later st age. Any underlying bladder dysfunction should be diagnosed and treated. POSTERIOR URETHRAL VALVES (PUV) 675 Long-term monitoring Monitor children for linear growth (height, weight, and head circumfer - ence), renal function, BP, urine analysis (for proteinuria, osmolality), USS, and formal GFR with chromium EDTA. Renography (MAG3 and DMSA) are also performed to assess split renal function and look for evidence of obstruction or re \202 ux. Videourodynamic studies are used to assess and aid in the management of any associated voiding dysfunction. Prognosis Thirty- \201 ve percent have long-term poor renal function; 20% develop end- sta ge renal failure. Bladder dysfunction is common despite treatment of out \202 ow obstructi on. This includes bladder overactivity, incontinence, and bladder underactivity associated with chronic urinary residuals and poor concentration of urine (with polyuria). From age 16 y, care should be transferred to an adult urologist or nephrologist. Problems may arise wit h retrograde ejaculation, impotence and reduced libido (related to renal impairment), and a bnormal prostatic or seminal vesicle secretions, con- tributing to reduced fertility. CHAPTER 16 Pediatric urology 676 Cystic kidney disease Congenital cystic kidney disease can be is classi \201 ed into non-g enetic and genetic types. Non-genetic Multicystic dysplastic kidney (MCDK) The cysts of a \200\230multicystic \200 \231 kidney are not due to dilatation of renal col- lecting ducts (as in polycystic disease ), but instead, the entire kidney is dysplastic and non-functioning, with immature dysplast ic stroma and non- communicating cysts of various sizes. The proximal ureter is atretic in about 66%. Incidence The incidence of unilateral MCKD is 1 in 4000, with a male to female ratio of 2:1 . Bilateral disease occurs in 10% of cases and is incompatible with life. Presentation MCDK is detected on antenatal USS (20 weeks \200\231 gestation). A 34-week ant enatal USS is performed to assess for contralateral anomalies. Clinical types and associated disorders MCKD may be simple (contralateral kidney is normal on USS) or com- plicated (contralateral side is abnormal). Unilateral disease is associated with VUR or PUJ obstruction in the contralateral kidney in 730%. An ure- terocele will be associated with MCKD in 10% of cases. Management Post-natal renal tract USS is performed at 1 week after birth. Simple MCDK This does not require prophylactic antibiotics. Repeat USS and DMSA renogram ar e performed at 6 weeks to con \201 rm there is no renal function in the MCDK. Affected kid neys (especially those <6cm) tend to involute. Most can be treated conservatively with surv eillance of growth, BP, urine analysis, and USS follow-up. Consider surgical removal for MC DK >6cm (which tend to grow), any solid component, hypertension, symptoms, or parental pref erence Complicated MCDK Prophylactic antibiotics are started at birth. Post-natal USS and MAG3 ren ogram are performed to investigate obstruction (i.e. contralateral PUJ obstruction). MCUG a nd DMSA renogram are performed to exclude re \202 ux. Risks The risk of developing hypertension or Wilms \200\231 tumor (see b p. 238) with MCDK is rare and routine nephrectomy to prevent the development of these conditions is no longer recommended. Follow-up of BP, growth, proteinuria, and renal tract USS is recommended. CYSTIC KIDNEY DISEASE 677 Multilocular cystic nephroma Presents in young children with a \202 ank mass, loin pain, or haematuria. Diagnosis is on USS or CT, demonstrating multilocular cysts in the renal par enchyma, which may extend into the collecting system. It is included in a spectrum of disea se that is closely associated with Wilms \200\231 tumor and so the recommended treatment us ed to be partial or full nephrectomy, but many specialists will monitor these now rather th an proceed directly to surgery. Genetic Autosomal recessive polycystic kidney disease (ARPKD) A disease of infancy and chil dhood where renal collecting tubules and ducts become cystically dilated and numerous small cysts form in the renal cortex and medulla bilaterally. Incidence of 1 in 10 000 \200\2234 0 000. Severe forms present early and have a poor prognosis. Prenatal USS demon- strates ol igohydramnios (amniotic \202 uid <200mL) and large, \200\230bright \200\231 homo- geneou sly hyperechogenic kidneys which can cause obstructed labor and respiratory problems (secon dary to pulmonary hypoplasia). Neonates have large \202 ank masses, limb and facial anoma lies. All cases are associ- ated with congenital hepatic \201 brosis. Infants may develop fatal uraemia and respiratory failure; older children present with renal failure, hyperten sion, and portal hypertension. Most develop end-stage renal failure by adult- hood, requiri ng haemodialysis, nephrectomy (to control hypertension), and subsequent renal transplantati on. Autosomal dominant polycystic kidney disease (ADPKD) (see b p. 404) Typically presents in adulthood, although older children can present with complications of haematuria, \202 ank pain, \202 ank mass, UTI, proteinu- ria, hypertension, and intracerebral bleeds (seco ndary to berry aneurysm rupture). ADPKD is the most commonly inherited renal disease with a n incidence of 71 in 1000. It is characterized by multiple expanding cysts of both kidneys that ultimately destroys the intervening parenchyma and accounts for 10% of all chronic ren al failure. Ninety percent of cases are due to a defective PKD1 gene located on chromosome 16; the remainder is due to a defective PKD2 gene on chromosome.4 Familial juvenile nephronophthisis An autosomal recessive disorder which develops in early childhood and accounts for up to 20% of pediatric renal failure. Medullary cystic dis- ease is a similar (autosomal dominant) condition which develops in later childhood. Histology i n both conditions shows interstitial nephritis associ- ated with corticomedullary cysts. Di sease progression causes a reduction in kidney size. Features include polyuria and polydips ia (due to a salt-losing nephropathy), anemia, growth retardation, hypertension, and chroni c renal failure. Initial treatment includes salt replacement. Dialysis and renal transplant ation are later options. Others Renal cysts are also a feature of autosomal dominant conditions, including von Hippe l \200\223Lindau syndrome (cerebellar and retinal haemangioblasto- mas, phaeochromocytoma, pancreatic cysts, renal cell carcinoma (RCC)) and tuberous sclerosis (adenoma sebaceum, epi lepsy, learning dif \201 culties associated with renal angiomyolipoma, and RCC). CHAPTER 16 Pediatric urology 678 Hypospadias Hypospadias is a congenital deformity where the opening of the ure- thra (the m eatus) is sited on the underside (ventral) part of the penis, anywhere from the glans to th e perineum. It is often associated with a \200\230hooded \200\231 foreskin (prepuce) and c hordee (ventral curvature of the penile shaft). It occurs in 1 in 250 live male births. The re is an 8% incidence in offsprings of an affected male and a 14% risk in male siblings. Classi \201 cation Hypospadias can be classi \201 ed according to the anatomical location of the urethral meatus (Fig. 16.6). Most common are anterior hypospadias accounting for 50 \200\22380% of cases. - - - Anterior Middle Posterior (or distal): glandular, coronal, and subcoronal. : distal penile, midshaft, and proximal penile. (or proximal): penoscrotal, scrotal, and perineal. Etiology Hypospadias results from incomplete closure of urethral folds on the undersurface of the penis during embryological development. This is related to a defect in the productio n or metabolism of fetal androgens or the number and sensitivity of androgen receptors in t he tissues. Chordee is caused by abnormal urethral plate development or an intrinsic abnor- mality of the corpora cavernosa and the \200\230hooded \200\231 foreskin is due to failed fusion of the preputial folds (resulting in a lack of ventral foreskin). Associated anomalies - Undescended testes. - Inguinal hernia - Disorders of sexual developm ent (i.e. mixed gonadal dysgenesis). - Persistence of M llerian structures (i.e. dilated u tricle). hydrocele. Diagnosis A full clinical examination to establish the diagnosis, assess the penis and uret hral plate, and detect associated abnormalities needing treat- ment. Patients with unilater al or bilateral absent or impalpable testes and hypospadias should undergo chromosomal and endocrine investiga- tion to exclude disorders of sex development. Posterior hypospadias ca n be associated with other urinary tract malformations and requires USS investigation. Treatment Surgery is indicated where deformity is severe, interferes with voiding, or is pr edicted to interfere with sexual function. Repair is performed between 6 \200\22318 months of age. Androgens have been used preoperatively to help increase tissue size. Surgery aims to correct penile curvature (ortho- plasty), reconstruct a new urethra, and bring the new m eatus to the tip of the glans using urethroplasty, glansplasty, and meatoplasty techniques. HYPOSPADIAS 679 Single-stage repair Distal (and selected cases of middle and proximal hypospadias) can be t reated by a Snodgrass procedure (tubularized incised plate (TIP) urethro- plasty). The peni s is degloved and an arti \201 cial erection created to assess for chordee which may be co rrected with dorsal plication. The glans wings are incised to separate them from the urethr al plate which is incised in the midline to widen it and allow tubularization and a layered suture closure over a catheter. A dartos pedicle is used to cover the repair. Reconstructi on of the glans is with layered suture repair (glansplasty).The catheter is removed 7 days later. Two-stage repair (free graft repair) Many proximal and some middle hypospadias may require a two-stage procedure which consists of initial preparation of the urethral plate and inser tion of a free graft (prepuce or buccal mucosa). A \201 ne catheter is placed into the bl adder and an occlusive dressing applied. The dressing is removed under general anesthesia a round 7 days later, the graft examined for viability, and the catheter removed. The second stage of tubularization of the neo-urethra and closure is performed around 6 months later. Other repairs described for hypospadias Distal hypospadias repairs - urethroplasty. - TIP Tubularization (Thiersch Duplay). Operation of choice if wide urethral plate and deep g lans groove available for reconstruction. Meatal advancement and glanuloplasty ( Meatal-bas ed \202 aps (Mathieu procedure). MAGPI). Middle hypospadias repairs - urethroplasty. - - - TIP Tubularization (Thiersch Duplay). Onlay island \202 ap ( Meatal-based \202 aps. OIF) using a preputial graft. Proximal hypospadias repairs - - - - Free graft (two-stage repair). Transverse preputial island \202 ap ( OIF TIP TPIF). repair. urethroplasty. Complications Overall complication rate of 4 \200\2237% in the short to medium term. Compli cations increase with time and severity of hypospadias. They include urethrocutaneous \201 stula, urethral stricture, meatal stenosis, spray- ing of urine, voiding dysfunction, urethral diverticulum, recurrent chordee, sexual dysfunction, poor cosmesis, and failure of repair or graft requiring re-operation. CHAPTER 16 Pediatric urology 680 glanular coronal subcoronal distal penile midshaft Anterior (distal) middle proximal penile penoscrotal scrotal posterior (proximal) perineal Fig. 16.6 The anatomical classi \201 cation of hypospadias according to the location of th e urethral meatus. This page intentionally left blank CHAPTER 16 Pediatric urology 682 Disorders of sex development See Tables 16.6 and 16.7. Disorders of sex development (DSD) are de \201 ned as congenital conditions in which the d evelopment of chromosomal, gonadal, or anatomical sex is atypical. They are estimated to af fect 1 in 4500 births. DSD is divided into: - Sex chromosome DSD (disorders of gonadal differentiation): these include conditions with se miniferous tubule dysgenesis (Klinefelter \200\231s syndrome 47XXY and 46XX testicular DSD) , Turner \200\231s syndrome (45XO), ovotesticular DSD (46XX/46XY, 46XX, or 46XY with both o varian and testicular tissue and ambiguous genitalia), mixed gonadal dysgenesis 45XO/46XY m osaicism (streak gonads and a spectrum of ambiguous genitalia), and 46XX (pure) gonadal dys genesis (females with streak gonads). Refer to summary (Table 16.6). 46XY DSD karyotype wit h defects of testosterone production (3B-hydroxysteroid dehydrogenase or 17A-hydroxylase en zyme de \201 ciencies; testicular dysgenesis; Leydig cell aplasia) or defects of testoster one metabolism (5A-reductase de \201 ciency), resulting in varying degrees of feminization . Also included are disorders of MIS or MIS receptor defects, resulting in persistent M ll erian duct syndrome (male phenotype with uterus, Fallopian tubes, and upper vagina). (previously male pseudohermaphroditism): 46XY Complete androgen insensitivity syndrome (CAIS), caused by andro- gen resistance, is the mo st common cause of 46XY DSD. Where the family history is positive, karyotyping can be perfo rmed at birth. Sporadic cases are dif \201 cult to detect. In CAIS, the phenotype and exte rnal genitalia are female, however, internal genitals are usually absent (or rudimentary). At puberty, there is breast development, scanty pubic and axillary hair, a short blind-endi ng vagina, and patients are often tall. They may present at this time for investigation of primary amenorrhoea, with raised LH and testosterone. Undescended testes may be palpable in the inguinal canal and will require removal after puberty due to malignancy risk. Estrogen replacement is then given. In comparison, incomplete or partial androgen insensitivity syndrome (PAIS) presents with a wide spectrum of phenotypes, most commonly with a degree of ambiguous genitalia. - 46XX DSD karyotype with ovaries and internal genitalia, but a partially masculinized phenot ype and ambiguous external genitalia due to intrauterine exposure to androgens. (previously female pseudohermaphroditism): 46XX The most common type is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase de \201 ciency (in 95%), an autosomal recessive disorder. CAH accounts for around 85% of all infan ts with ambiguous genitalia. Formation of hydrocortisone is impaired, resulting in a compen satory increase in adrenocorticotrophin hormone (ACTH) and testosterone production. Some fo rms have a \200\230salt-wasting \200\231 aldosterone de \201 ciency which can present in the \201 rst few weeks of life with adrenal crisis (severe vom- iting and dehydration), r equiring rehydration and steroid replacement DISORDERS OF SEX DEVELOPMENT 683 therapy with mineralocorticoids and glucocorticoids. Rarer causes of CAH are 11B-hydroxylas e de \201 ciency and 3B-hydroxysteroid dehydrogenase de \201 ciency (see Fig. 16.7). Disorders of ovarian development (i.e. 46XX gonadal dysgenesis, 46XX testicular DSD) can also be included in this category. Evaluation - A detailed Maternal ingestion of drugs such as steroids or contraceptives duri ng pregnancy should be ascertained. General (Klinefelter \200\231s and Turner \200\231s syn dromes) or failure to thrive and dehydration (salt-wasting CAH). Assess external genitalia for phallus size and location of urethral meatus. Careful palpation may con \201 rm the pr esence of testes which excludes a diagnosis of 46XX DSD. Patients with bilateral undescende d testes or unilateral undescended testis with hypospadias should be also suspected of havi ng a DSD. Abdominal/pelvic Diagnostics laparoscopy or laparotomy required to clarify diagno sis. Chromosomal analysis Serum tests test for salt-wasting CAH. A raised serum 17-hydroxyp rogesterone is seen in 21-hydroxylase de \201 ciency. HCG stimulation test can diagnose an drogen resistance and 5A-reductase de \201 ciency. history may uncover a positive family history of DSD. examination may show associated syndrome anomalies USS can help locate the gonads. with gonadal biopsy may be con \201 rms karyotype. : serum electrolytes, testosterone, and DHT analysis Management A multidisciplinary approach is required with full parental input. In cases of a mbiguous genitalia, advise parents to delay registering the birth until a diagnosis is esta blished and gender has been assigned. The Registry Of \201 ce has special provision for th is situation. Gender assignment of ambiguous genitalia is guided by the functional potentia l of gonadal tissue, reproduc- tive tracts, and genitalia, with the aim of optimizing psych osocial well-being and producing a stable gender identity. This is ultimately decided by a full multidisciplinary team (pediatric urologists, endocrinologist, geneticists, and psycho logists) in tertiary specialist centers. Patients have a higher risk of gonadal malignancy, which requires surveillance and/or removal of gonadal tissues and hormone replacement. Pat ients with hypogonadism will require hormone replacement and arti \201 cial induction of p uberty. CHAPTER 16 Pediatric urology 684 Cholesterol 17A-OH 17,20-Lyase Pregnenolone 17-OH Pregnenolone Dehydroepiandrosterone 3B-HSD 3B B-HSD 3 DSH- 17A-OH 17,20-Lyase Progesterone 17-OH Progesterone Androstenedione 17B-HSD 21-OH 21-OH 11-deoxycorticosterone 11-deoxycortisol Testosterone 5A-reductase Aromatase 11B-OH 11B-OH Corticosterone Cortisol Dihydrotestosterone Oestradiol 18-OH 18-OH corticosterone 18-oxidase Aldosterone Key: 17-OH 21-OH 3B-HSD 3B-hydroxysteriod dehydrogenase 11B-OH 11B-hydroxylase 17A-hydroxylase enzyme 21-hydroxylase Fig. 16.7 Metabolic pathways for adrenal steroid synthesis. Table 16.6 Proposed revised nomenclature1 Old terminology Proposed new terminology Intersex Disorders of sex development (DSD) Male pseudohermaphrodite 46,XY DSD Female pseudohermaphrodite 46,XX DSD True hermaphrodite Ovotesticular DSD Testicular feminization Androgen insensitivity syndrome, complete (CAIS) 46XX male 46XX testicular DSD 1 Hughes IA, Houk C, Ahmed SF, et al. (2006) Consensus statement on management of intersex disorders. Arch Dis Child 91(7):554 \200\22363. Table 16.7 Disorders of sex development Disorder Karyotype Gonad Genitalia Other features Treatment Disorder of gonadal differentiation Androgen replacement Male Tall, gynaecomastia, azoospermia, mild mental retardation, i FSH/LH, d testosterone Klinefelter \200\231s syndrome 47XXY Seminiferous tubule dysgenesis, small testes 46XX testicular DSD 46XX (SRY +ve) Seminiferous tubule dysgenesis Male Shorter stature, gynaecomastia, infertile, hypospadias, i FSH/LH, d testosterone Short stat ure, sexual infantilism, web neck, widespread nipples, wide carrying angle, coarctation, re nal anomalies Androgen replacement Turner \200\231s syndrome 46XO Streak ovaries Female Growth hormone, estrogen replacement therapy D I S O R D E R S O F Ovotesticular DSD 46XX, XY, 46XX/46XY Ovary and testis Ambiguous or male Hypospadias (80%) in \200\230males \200\231; cliteromegaly in \200\230females \200\231 Gender assignment surgery Mixed gonadal dysgenesis 46XO/46XY Unilateral undescended testis and streak gonad Ambiguous Wide phenotypic spectrum from Turner \200\231s syndrome-like female to male. Includes hypos padias Gender assignment, gonadectomy (as i cancer risk), screen for Wilms \200\231 tumor S E X D E V E L O P M E N T 46XX \200\230pure \200\231 gonadal dysgenesis 46XX Streak ovaries Female Normal stature, sexual infantilism, primary amenorrhoea Cyclic hormone replacement (Continued) 6 8 5 6 8 6 C H A P T E R 1 6 Table 16.7 (Continued) Disorder Karyotype Gonad Genitalia Other features Treatment P a e d i a t r i c 46XY DSD 3 -dydroxysteroid dehydrogenase Salt-wasting, d cortisol, d aldosterone 46XY Testes Ambiguous Glucocorticoid and mineralocorticoid replacement 17A-hydroxylase de \201 ciency d Cortisol (causing i ACTH), resulting in d steroids, hypokalaemia, hypertension 46XY Testes Ambiguous Glucocorticoid replacement u r o l o g y Complete androgen insensitivity syndrome 46XY Testes Female Androgen resistance, female phenotype, short blind-ending vagina, breasts at puberty Gonadectomy after puberty, estrogen replacement therapy Gender assignment surgery 9 gonadec tomy and hormone Incomplete androgen insensitivity syndrome 5A-reductase de \201 ciency 46XY Testes Ambiguous Wide spectrum, including hypospadias, infertility, gynaecomastia, pseudovagina Reconstructive surgery 9 hormonal support 46XY Testes Ambiguous Failure to convert testosterone to DHT in androgen-sensitive cells, hypospadias, small phal lus, short vagina, virilization at puberty 46XX DSD Glucocorticoid, mineralocorticoid replacement and surgery Congenital adrenal hyperplasia 46XX Ovaries Ambiguous Simple virilization or salt-wasting aldosterone de \201 ciency Virilization by maternal drug use in pregnancy or maternal adrenal tumors Transplacental androgens External genitalia reconstruction as required 46XX Ovaries Ambiguous D I S O R D E R S O F S E X D E V E L O P M E N T 6 8 7 CHAPTER 16 Pediatric urology 688 Exstrophy \200\223epispadias complex Exstrophy \200\223epispadias complex describes a spect rum of congenital malformations affecting the abdominal wall, pelvis, genitourinary tract, and sometimes also the spine and anus. It includes bladder exstrophy, epispa- dias, and clo acal exstrophy. Classic bladder exstrophy This is the most common manifestation and results from defective devel- opment of the anterior bladder and lower abdominal walls, resulting in the posterior bladder wall lying exposed on the abdomen. Virtually all cases are associated with epispad ias (see b p. 690). Epidemiology: incidence is 71 in 30 000 live births. Male to female ratio is 5:1. Increased risk in offspring of affected patients and with younger maternal age and increased parity. Embryology: classically described as an embryological malformation caus- ing abnormal overd evelopment of the cloacal membrane, which prevents in-growth of lower abdominal (mesenchyma l) tissues. The cloacal mem- brane normally perforates to form the urogenital and anal open ings, but in exstrophy, premature rupture results in a triangular defect below the umbilicu s. The timing of rupture determines the type of resulting defect (bladder exstrophy, cloaca l exstrophy, or epispadias). Other theories challenge this and suggest abnormal development of the bony pelvis or maldevelopment of the genital hillocks below their normal position, with midline fusion below rather than above the cloacal membrane (resulting in premature cl oacal rupture prior to mesenchymal in-growth). Associated anomalies - Bone defects outward rotation of the pelvic bones along the sacroiliac joints. Musculofasci al defects of rectus abdominis, abnormal pelvic \202 oor, low lying umbilicus. Genital de fects the corporal cavernosa, short urethral plate, epispadias, de \201 ciency of dorsal f oreskin. Females \200\224bi \201 d clitoris, stenotic vaginal ori \201 ce, short anterior ly placed vaginal canal, uterine prolapse in adult life. Urinary tract defects due to later al displacement of the ureteric ori \201 ces. GI anal sphincter contributes to fecal incon tinence. : diastasis (widening) of the symphysis pubis due to : umbilical hernias, inguinal hernias, divarication : Males \200\224short, broad penis with lateral splaying of : exposed bladder plate; majority suffer VUR tract defects: anteriorly displaced anus, rectal prolapse, abnormal Investigation Typical features seen on prenatal USS include a lower abdominal wall mass, ab sent bladder \201 lling, low-set umbilicus, small genitalia, abnormal iliac crest widenin g. Diagnosis can help planning of delivery in a center with facilities to perform early sur gical correction. EXSTROPHY \200\223EPISPADIAS COMPLEX 689 Management At birth, cover the bladder with plastic \201 lm and irrigate regularly with s terile saline. Trauma to the bladder mucosa can result in squamous meta- plasia, cystitis c ystica or adenocarcinoma, and squamous cell carcinoma after chronic exposure. Surgery: aims to provide a continent reservoir for urine storage, preserve renal function, and create functional and cosmetically acceptable external genitalia. Selected cases are su itable for a one-stage complete primary repair of bladder exstrophy (CPRE), involving closu re of the bladder plate and epispadias repair. However, many require staged procedures. - N ewborn : pelvic osteotomy (cutting bone to correct deformity) with external \201 xation a nd closure of bladder, abdominal wall, and posterior urethra. 6 \200\22318 months 4 \200 \2235y : bladder neck reconstruction (Young \200\223Dees \200\223Leadbetter procedure) and anti-re \202 ux surgery (ureteric re-implantation) is performed when there is adequate bla dder capacity and children can participate in voiding protocols. Where bladder capacity is too small, bladder augmentation and/or urinary diversion is required. : epispadias repair (see b p. 689). Surgical complications: increased risk of malignancy in urinary or ortho- topic bladder, \201 stula, hypospadias, bladder stones, infection (UTI, epidi- dymitis), incontinence. Cloacal exstrophy This is the most severe form of exstrophy \200\223epispadias complex. Cha racterized by an exomphalos (midline abdominal defect with bowel covered in a thin sac of a mnion and peritoneum), below which are two halves of an exstrophied bladder separated by an exstrophied bowel seg- ment. It is associated with a bi \201 d or micro-penis and the abs ence of one or both testes. The incidence is between 1 in 200 000 and 1 in 400 000; male to female ratio is 6:1. There is a high risk of associated congenital anomalies. Surgical rec onstruction may require terminal colostomy, pelvic osteotomy, anterior bladder reconstructi on augmentation cystoplasty. Gender assignment may need to be considered in males. CHAPTER 16 Pediatric urology 690 Primary epispadias In epispadias, the urethra opens onto the dorsal surface of the penis, a ny- where from the glans, penile shaft, or most commonly, the penopubic region. An incomple te urethral sphincter mechanism (seen with posterior urethral epispadias) results in a high risk of incontinence. Epispadias is also associated with dorsal chordee (causing an upward curvature of the penis) and with incomplete foreskin dorsally. Epispadias is part of the e xstrophy \200\223 epispadias complex (see b p. 688). Primary epispadias (without exstro- ph y) is rare. Associated anomalies Diastasis of the symphysis pubis results in splaying and rotation of t he corpora cavernosa, laterally placed neurovascular bundles, and shortening of the penile shaft. There is reduced male fertility, with paternity rates of 736%. Females have a bi \201 d clitoris, poorly developed labia, and demon- strate a spectrum of urethral deformiti es, ranging from a patulous urethral ori \201 ce to a urethral cleft affecting the entire length of the urethra and sphincter. There is >40% risk of VUR which commonly requires uret eric re-implantation. Incidence: affects 1 in 117 000 males; rarely seen in females (1 in 400 000).