10.5 Clinical Features	291

•The AMH gene provides instructions for making a protein called anti-Müllerian hormone (AMH).

•The AMHR2 gene provides instructions for making a protein called AMH receptor type II.

•The AMH protein and AMH receptor type II protein are involved in male sex differentiation.

•During development of a male fetus, these two proteins work together to induce breakdown (regression) of the Müllerian duct.

•Mutations in the AMH and AMHR2 genes lead to nonfunctional proteins that cannot signal for regression of the Müllerian duct.

•As a result of these mutations, the Müllerian duct persists and goes on to form a uterus and fallopian tubes.

•Approximately 45 % of cases of persistent Müllerian duct syndrome are caused by mutations in the AMH gene and are called persistent Müllerian duct syndrome type 1.

•Approximately 40 % of cases are caused by mutations in the AMHR2 gene and are called persistent Müllerian duct syndrome type 2.

•In the remaining 15 % of cases, no mutations in the AMH and AMHR2 genes have been identified, and the genes involved in causing the condition are unknown.

•This condition is inherited in an autosomal recessive pattern. However, persistent Müllerian duct syndrome affects only males. Females with two mutated copies of the gene do not show signs and symptoms of the condition.

•PMDS type I results from mutations of the gene (AMH) for AMH on chromosome 19p3.3.

•PMDS type II results from mutations of the gene (AMH-RII) for the AMH receptor on 12q13.

10.4Classification of PMDS

•Classically, patients with PMDS present with unilateral or bilateral cryptorchidism and they have normal male genotypes and phenotypes.

•Two anatomic variants of PMDS have been described: male and female.

–The male form:

•This is the most common form encountered in 80–90 % of cases.

•It is characterized by unilateral cryptorchidism with contralateral inguinal hernia, and can be one of two types:

–The first type is hernia uteri inguinalis, which is characterized by one descended testis and herniation of the ipsilateral corner of uterus and fallopian tube into the inguinal canal.

–The second type is crossed testicular ectopia, which is characterized by herniation of both testes and the entire uterus with both fallopian tubes on the same side.

–The female form:

•This is seen in 10–20 % of cases.

•It is characterized by bilateral cryptorchidism.

•The gonads are usually within the pelvis, with the testes fixed within the round ligament in the ovarian position with respect to the uterus.

10.5Clinical Features

•Patients with persistent Müllerian duct syndrome usually present with undescended testes (cryptorchidism) which can be unilateral or bilateral.

•More often, one testis has descended into the scrotum normally, and the other one has not. In these cases, the uterus and fallopian tubes are in the pelvis.

•In cases of unilateral or bilateral cryptorchidism associated with hernia, the possibility of PMDS should be kept in mind (Fig. 10.1).

•Sometimes they present with inguinal hernias (Fig. 10.2).

•Sometimes, the descended testis pulls the fallopian tube and uterus into the track through which it has descended and into the inguinal hernia sac. This condition is called hernia uteri inguinalis, a form of inguinal hernia in which the hernia sac contains the uterus and Fallopian tubes.

•In some cases with persistent Müllerian duct syndrome, they present with bilateral undescended testes and the undescended testis from one side is also pulled into the other side,

292	10 Persistent Müllerian Duct Syndrome (PMDS)

Fig. 10.1 A clinical photograph of a patient with normal looking external genitalia and undescended right testis who was found to have deficiency of MIS

TESTIS
		UTERUS		TESTIS

FALLOPIAN

TUBES

FALLOPIAN

TUBES

Fig. 10.3 A clinical intraoperative photograph of a patient with persistent Müllerian duct syndrome. Note the presence of a uterus, two fallopian tubes and two testes but no ovaries. This results from deficiency of MIS. Note also the testes fixed within the round ligament in the ovarian position with respect to the uterus

Fig. 10.2 A clinical photograph of a patient with normal looking external genitalia and a large right inguinal hernia who was found to have deficiency of MIS

forming an inguinal hernia with both undescended testes on the same side. This condition is called transverse testicular ectopia.

•The uterus and fallopian tubes are typically discovered intraoperatively when surgery is performed to treat undescended testes or inguinal hernia (Fig. 10.3).

•Sometimes the uterus and fallopian tubes are discovered preoperatively via ultrasound or MRI while investigating impalpable undescended testes or for other reasons.

•Some of these cases may remain undiagnosed to present late with infertility or blood in the semen (hematospermia). Infertility in these

patients may be primary from the testes or secondary to obstruction or nonpatency of the vas deferens.

•Since the patients are phenotypically male, the diagnosis is usually not suspected and the diagnosis is delayed or made at the time of surgery for cryptorchidism or hernia.

•The risk of malignancy in an ectopic testis in a case of PMDS is similar to that in a cryptorchid testis in a healthy male. Germ cell tumors have been reported in the testis, whereas tumors of the Mullerian duct derivatives are very rare.

10.6Treatment

•The aim of surgical treatment is to mobilize, preserve and fix the testes in the scrotum without injuring the vessels and vas.

•The associated hernia should also be treated.

•During surgery, the uterus is usually removed and attempts are made to dissect away Müllerian tissue from the vas deferens and epididymis without injuring them to improve the chance of fertility.

•A vas deferens is presents bilaterally, usually running close to the uterus.

•To avoid damage to the vas, care must be taken at the time of Müllerian remnants excision.

•Rarely, the vas deferens ends blindly.

Further Reading	293

•With the recent advances of minimal invasive surgery, laparoscopic hysterectomy is an alternative technique to improve the chances of fertility in these patients.

•The surgical management of PMDS includes:

–Orchidopexy:

•Every attempt should be made to preserve the testes, vas and vessels.

•This may necessitates division of the uterus to lengthen the vas.

•A transverse testicular ectopia may be associated with this condition. In this, both testes are found on the same side and both testes should be mobilized and fixed one in each scrotum.

–Excision of Müllerian remnants:

•This is not a simple procedure and care should be taken to avoid injury to the vas.

•In those where removal of the Müllerian remnants is not possible, division of the uterus can be done to lengthen the vas and facilitates orchidopexy.

•Removal of Müllerian remnants is unnecessary, since the remnants rarely produce symptoms and there is an extremely rare risk of subsequent malignancy.

10.7Prognosis

•The prognosis depends upon the integrity of the testicular tissue and successful correction of cryptorchidism, which is often complicated by the close anatomical relationship between the vas deferens and the Mullerian derivatives

•The risk of malignancy in an ectopic testis in a case of PMDS is similar to that in a healthy male, with the incidence being 15 %. There have been case reports of embryonal carcinoma, seminoma, yolk sac tumor and teratoma

in patients with PMDS, whereas tumors of the Mullerian duct derivatives are very rare.

•Infertility is common in these patients, with an absence of spermatozoa or results secondary to obstruction or nonpatency of the vas deferens.

Further Reading

1. Asthana S, Deo SV, Shukla NK, Raina V, Kumar L. Persistent Mullerian duct syndrome presenting with bilateral intra-abdominal gonadal tumors and obstructive uropathy. Clin Oncol. 2001;13(4):304–6.

2. Clemente A, Macchi V, Berretta M, Morra A. Female form of persistent Müllerian duct syndrome: MDCT findings. Clin Imaging. 2008;32:314–7.

3. Crankson SJ, Bin Yahib S. Persistent Mullerian duct syndrome in a child: surgical management. Ann Saudi Med. 2000;20:267–9.

4.El-Gohary MA. Laparoscopic management of persistent Mullerian duct syndrome. Pediatr Surg Int.

2003;19(7):533–6.

5. Guerrier D, Tran D, Vanderwinden JM, Hideux S, Van Outryve L, Legeai L, et al. The persistent Mullerian duct syndrome: a molecular approach. J Clin Endocrinol Metab. 1989;68:46–52.

6. Gutte AA, Pendharkar PS, Sorte SZ. Transverse testicular ectopia associated with persistent Mullerian duct syndrome – the role of imaging. Br J Radiol. 2008;81:E176–8.

7. Loeff DS, Imbeaud S, Reyes HM, Meller JL, Rosenthal IM. Surgical and genetic aspects of persistent Mullerian duct syndrome. J Pediatr Surg. 1994;29:65–6.

8. Martin EL, Bennett AH, Cromie WJ. Persistent Mullerian duct syndrome with transverse testicular ectopia and spermatogenesis. J Urol. 1992;147: 1615–7.

9. Ng JWT, Koh GH. Laparoscopic orchidopexy for persistent Mullerian duct syndrome. Pediatr Surg Int. 1997;12:522–5.

10. Renu D, Ganesh Rao B, Ranganath K, Namitha. Persistent Mullerian duct syndrome. Indian J Radiol Imaging. 2010;20(1):72–4.

11.Shamim M. Persistent Mullerian duct syndrome with transverse testicular ectopia presenting in an irreducible recurrent inguinal hernia. J Pak Med Assoc. 2007;57(8):421–3.

Neurogenic Bladder Sphincter	11
Dysfunction

11.1Introduction

•Neurogenic bladder sphincter dysfunction (NBSD) can develop as a result of a lesion at any level in the nervous system, including:

–The cerebral cortex

–The spinal cord

–The peripheral nervous system

•In the pediatric age group, neurogenic bladder sphincter dysfunction can develop as a result of congenital or acquired causes.

•Commonly it results from congenital neural tube defects including:

–Myelomeningocele

–Lipomeningocele

–Spina bifida

–Sacral agenesis

–Tethered cord

•Acquired causes include:

–Spinal cord tumors

–Spinal cord trauma

–Transverse myelitis

•Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction and the symptoms depend on the site of neurological insult.

–The effect on detrusor muscle:

•Detrusor underactivity

•Detrusor overactivity

–The effect on urinary sphincter:

•Sphincter underactivity

•Sphincter overactivity and loss of coordination with bladder function.

•The management of children with neurogenic bladder sphincter dysfunction is similar irrespective of the underlying cause.

•The aim is:

–Early diagnosis

–Early medical treatment

–To prevent the adverse effects on the bladder which subsequently will lead to incontinence and secondary damage to the kidneys.

•The management of NBSD in children has undergone major changes over the years.

–One of the most important advancement was the introduction of clean intermittent catheterization (CIC).

–The second important aspect of their management was the use of anticholinergics.

–The third important breakthrough in their management is the wide use of urodynamic studies to diagnose these patients, classify their defect and institute early and proper treatment.

•CIC, combined with anticholinergics when necessary has made “conservative” management of children with NBSD a successful treatment option, with a good outcome in term of:

–Quality of life of these children

–Avoiding damage to the kidneys

•Urodynamic assessment is essential for the diagnosis and prognosis of pediatric neurogenic bladder.

•Urodynamic studies are functional studies of the lower urinary tract; they evaluate storage and emptying functions of the bladder.

© Springer International Publishing Switzerland 2017	295
A.H. Al-Salem, An Illustrated Guide to Pediatric Urology, DOI 10.1007/978-3-319-44182-5_11