ORIGINAL ARTICLE

Grace Chew Æ John M. Hutson

Incidence of cryptorchidism and ascending testes in Trisomy 21:a 10 year retrospective review

Accepted: 17 September 2004 / Published online: 28 October 2004� Springer-Verlag 2004

Abstract Children with Down syndrome have an in-creased risk of cryptorchidism, but the reported inci-dence is unclear. In a proportion of these children, thetestes are within the scrotum at birth but later appear tohave ascended to an ectopic position. Records of pa-tients diagnosed with trisomy 21 who had surgery forundescended testes in two tertiary paediatric centresover a 10-year period were examined. Information onliveborn males with Down syndrome was obtained fromthe Victorian Genetic Registry, and then the incidence ofcongenital and acquired undescended testes was deter-mined. The incidence of undescended testes in Downsyndrome was found to be 6.52% (24/368), with 4.35%(16/368) being acquired undescended or ascending tes-tes. In conclusion, there is an increased incidence ofcryptorchidism in Down syndrome; in particular, thereis a significant proportion of acquired undescendedtestes.

Keywords Cryptorchidism Æ Ascending testes ÆDown syndrome Æ Paediatric

Introduction

Down syndrome occurs in one in 650–1,000 live births,caused by duplication of the distal long arm of chro-mosome 21. This condition has been associated withmental deficiency, cardiac anomalies, and gastrointesti-nal abnormalities, as well as an increased incidence of

cryptorchidism. Various sources suggest that the inci-dence is 5–6%; however, the true incidence of unde-scended testes and the proportion that are ascendedtestes in Down syndrome males is unclear. Ascendingtestes have been noted in children with normally des-cended testes in infancy, who then present with unde-scended testes at an older age. In our study, we definedascending testes as those in patients who present withundescended testes after 1 year of age and who previ-ously had testes present within the scrotum in infancy.Studies have suggested that this situation is due to fail-ure of normal growth of the spermatic cord, where afibrous remnant of the processus vaginalis remains at-tached to the tunica vaginalis and thus prevents normalelongation [1]. We conducted a retrospective review ofDown syndrome males who underwent orchidopexyover a 10-year period in two tertiary paediatric centresto ascertain the incidence of undescended and ascendedtestes.

Method

The medical records of the two Victorian state tertiarypaediatric centres were searched for males with tri-somy 21 who underwent orchidopexy between January1992 and December 2001. Their dates of birth, dates ofdiagnosis and surgery, side and site of undescendedtestes, and macroscopic appearance were noted. Orchi-dopexy for undescended testes was performed via aninguinal skin crease and median raphe, with excision ofany hydatid of Morgagni in the majority of cases at thetwo hospitals. The Victorian Genetic Registry wascontacted to determine the number of males with tri-somy 21 who were born in the state over the 10-yearperiod (Table 1). From the data, the age of diagnosis ofundescended testes and incidence were calculated. Inparticular, the incidence of congenital undescended tes-tes was determined from the number of males with tri-somy 21 and undescended testes diagnosed before 1 yearof age, while the incidence of acquired undescended

G. Chew (&) Æ J. M. HutsonDepartment of General Surgery, Royal Children’s Hospital,Melbourne, AustraliaE-mail: chewll2@yahoo.com.auTel.: +61-402-838726Fax: +61-3-9345-6668

J. M. HutsonDepartment of Paediatrics, University of Melbourne andDouglas Stephens Surgical Research Laboratory, MurdochChildrens Research Institute, Victoria, Australia

Pediatr Surg Int (2004) 20: 744–747DOI 10.1007/s00383-004-1290-8

testes or ascending testes was calculated from the num-ber of males with trisomy 21 and undescended testesdiagnosed after 1 year of age.

Results

In one of the patients (22), the diagnosis of undescendedtestes on the right was made at 7 years of age, and heunderwent orchidopexy. Four years later, he had recur-rence of his right cryptorchidism as well as contralateralundescended testis requiring surgery. Another patient(19) was coded as having bilateral orchidectomy forundescended testes; however, no histology report of thetestes was found, suggesting that this was a coding errorand that orchidopexy had actually been performed.

Of the 24 patients with undescended testes, eight werediagnosed before 1 year of age and 16 after the age of1 year. The majority had surgery after the age of 1 year,only two before 1 year. Of these 24, 11 were bilaterallyundescended, with three patients under 1 year of age(Table 2). The macroscopic appearance of three of35 testes examined intraoperatively was small, theremainder being normal.

According to the records of the Victorian GeneticRegistry, there were 368 liveborn males with Down

syndrome from 1992 to 2001. Given that most referralsin Victoria for young children with syndromes requiringurological surgery are expected to present to either ofthese two paediatric institutions, we expected to be ableto determine the minimal incidence of undescendedtestes from the information collected. As such, theincidence of undescended testes in Down syndrome wasfound to be at least 6.52% (24/368), of which 2.17% (8/368) were congenitally undescended and 4.35% (16/368)were ascending testes. In almost half of the children(45.83%, 11/24), cryptorchidism occurred bilaterally,with an incidence of 2.99% (11/368).

From Table 2, there were 3/11 (27.3%) males withtrisomy 21 and bilateral congenital undescended testescompared with 5/11 (45.5%) with unilateral congenitalundescended testes. In the population of trisomy 21males with ascending testes, there were 8/24 (50%) withbilateral acquired undescended testes and 8/24 (50%)with unilateral acquired undescended testes.

Discussion

The incidence of undescended testes is believed to behigher in trisomy 21 compared with the normal popu-lation, in whom the incidence of undescended testes has

Table 1 Details of Down syndrome males with undescended testes over a 10-year period (y year[s], m month[s], UDT undescended testes,EIR external inguinal ring, DIR deep inguinal ring, SIP superficial inguinal pouch)

Age at diagnosisof UDT

Age atsurgery

Sideof UDT

Site of UDT Surgery performed Macroscopicappearance

1 1 m 2 y 4 m Left High Orchidopexy Normal2 2 m 2 y 3 m Right Inguinal canal Orchidopexy Normal3 2 m 3 m Bilateral Right: inguinal

canal; left: DIROrchidopexy,circumcision

Normal

4 3 m 9 m Right Orchidopexy Small5 3 m 2 y 8 m Bilateral Inguinal canal Orchidopexy,

herniotomyNormal

6 5 m 1 y 10 m Left EIR Orchidopexy Normal7 8 m 4 y 5 m Right Inguinal canal Orchidopexy Normal8 10 m 4 y 2 m Bilateral Orchidopexy Small9 1 y 1 y 3 m Left DIR Orchidopexy10 1 y 8 m 1 y 9 m Right High Orchidopexy Normal11 1 y 10 m 1 y 11 m Left High Orchidopexy Normal12 2 y 2 y 7 m Bilateral Orchidopexy Normal13 2 y 2 y 4 m Left DIR Orchidopexy Normal14 3 y 2 m 3y 5m Bilateral Orchidopexy Right normal,

left small15 3 y 6 m 3 y 7 m Right Dartos pouch Orchidopexy Normal16 4 y 1 m 4 y 6 m Bilateral SIP Orchidopexy,

bilateral herniotomyNormal

17 6 y 5 m 7 y 2 m Bilateral EIR Orchidopexy Normal18 7 y 7 y Bilateral Inguinal canal Orchidopexy Normal19 7 y 5 m 9 y 4 m Bilateral SIP Orchidectomy20 8 y 5 m 8 y 5 m Left EIR Orchidopexy,

cystoscopy forlarge bladder

Normal

21 8 y 5 m 8 y 9 m Left EIR Orchidopexy Normal22 10 y 10 y 2 m Left SIP Orchidopexy Normal23 10 y 7 m Right: 7 y;

left: 11 y 1 mBilateral Right: EIR; left:

high inguinalLeft orchidopexyat same time asright redo orchidopexy

Normal

24 12 y 11 m 13 y 6 m Bilateral Orchidopexy, circumcision Normal

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been reported as 7.11% at birth and 1.58% at 3 months[2]. One source has suggested the incidence of cryptor-chidism in trisomy 21 to be as high as 14–27% [3]. In ourstudy, we found that the incidence was at least 6.52%(24/368).

With respect to acquired primary undescended testes,a study has shown a bimodal distribution of age at thetime of orchidopexy for undescended testes, with theorchidopexy rate in the older age group from 8 to11 years old being as high as 16% of orchidopexies [4].Reported orchidopexy rates have also been noted to beat least twice that expected from the incidence ofundescended testes [5]. However, in our study of maleswith trisomy 21, a significant proportion of undescendedtestes in these patients was acquired postnatally(66.67%) as opposed to congenital undescended testes(33.33%), where the youngest patient was 1 year and10 months and the oldest was 12 years and 11 months atthe time of diagnosis. In comparison with the normalpopulation in whom approximately half of undescendedtestes are congenital and half are acquired [4, 6], it ap-pears that a significantly larger proportion ascend after1 year of age in children with trisomy 21.

A mechanism proposed for primary acquired unde-scended testes is a failure of cord elongation rather thanmigration, due to a persistence of a fibrous remnant ofthe processus vaginalis deep to the spermatic fascia [1]. Itis possible that in trisomy 21, problems with both cordmigration along the path of the gubernaculum and im-paired cord elongation may be significant.

Furthermore, an association between Down syn-drome and hypogonadism has been noted, with elevatedFSH and LH in up to a third of patients [7]. A con-tributing factor to the increased incidence of congenitaland acquired undescended testes in this group may be adiminution of testicular function prenatally and post-natally. A recent study of young Down syndrome maleadults has reported a partial gonadal deficiency with asignificantly higher level of LH but normal FSH andtestosterone [8]; however, there is currently insufficientinformation in the literature on postnatal testosteronelevels in trisomy 21 to ascertain gonadal function in thepaediatric age group.

The conventional management for congenital unde-scended testes is orchidopexy by 6–12 months based on

deterioration of testicular histopathology if left uncor-rected [9], with experimental studies showing that earlyorchidopexy before maturation can prevent germ celldegeneration and restore spermatogenesis [10]. In ourstudy, all but two patients with congenital undescendedtestes proceeded to orchidopexy within 2 years of diag-nosis. These two patients were diagnosed at 10 monthsand 8 months, and proceeded to surgery at 4 years and2 months and 4 years and 5 months, respectively.

In the older age group with acquired undescendedtestes, most patients had orchidopexy within 6 monthsto 1 year, with the exception of one patient who hadsurgery within 2 years. From two prior studies of 25 and21 boys with ascending testes, the time to orchidopexywas within 2 years [1, 11]; thus, our treatment regimewas more stringent or at least in keeping with thosecentres. However, there is currently no clear recom-mendation in the literature regarding the best timing fororchidopexy in the older age group of patients withascending testes. Suffice it to say that there is a con-sensus that older patients with cryptorchidism have anincreased incidence of testicular malignancy. Specificallywith regard to Down syndrome, one study reported fourcases of Down syndrome and testicular cancer in pa-tients aged 29–35 years with stage 1 seminoma of thetestis. Of these, one had contralateral cryptorchidism[12]. Another 16 cases with the association of Downsyndrome and testicular germ cell cancer have previ-ously been reported [13]. A study based on the Texanpopulation found that 0.5% of all patients with testic-ular cancer had Down syndrome [14], while anotherstudy noted a 0.9% prevalence in an Irish population[15].

Of the three patients with small testes intraopera-tively, it would have been interesting to determine thelevels of FSH and LH because a negative correlationbetween testicular size and FSH has been documented[16]. Histological studies have indicated that there is alsoimpaired spermiosis with spermatogenic arrest and oli-gospermia.

From our study, we recommend that in the Downsyndrome male cohort who have not had orchidopexyfor congenital undescended testes, a need exists forongoing follow-up scrotal examinations at 6–12-monthintervals to identify patients with ascending testes later

Table 2 Number of Downsyndrome males withundescended testes

Number of patients(incidence %)

Total number ofundescended testes(incidence %)

Bilateral congenital undescended testes 3 (0.8)Unilateral congenital undescended testes 5 (1.35)Congenital undescended testes 8 (2.17)Total number of congenital undescended testes 11 (1.49)Bilateral ascending testes 8 (2.17)Unilateral ascending testes 8 (2.17)Ascending testes 16 (4.35)Total number of ascending testes 24 (3.26)Undescended testes 24 (6.52)Total number of undescended testes 35 (4.76)

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in childhood, given that up to two-thirds of undescendedtestes occur in the older age group in this population. Inaddition, accurate documentation of site, size, andconsistency of both testes is necessary. This is particu-larly significant given that two studies have reported theincidence of Down syndrome in testicular malignancy.

References

1. Clarnette TD, Rowe D, Hasthorpe S, Hutson JM (1997)Incomplete disappearance of the processus vaginalis as a causeof ascending testis. J Urol 157:1889–1891

2. John Radcliffe Hospital Cryptorchidism Study Group (1986)Cryptorchidism: an apparent substantial increase since 1960. BrMed J 293:1401–1404

3. Wilson GN, Cooley WC (2000) Preventive management ofchildren with congenital anomalies and syndromes. CambridgeUniversity Press, Cambridge, p 145

4. Fenton EJM, Woodward AA, Hudson IL, Marschner (1990)The ascending testis. Pediatr Surg Int 5:6

5. John Radcliffe Hospital Cryptorchidism Study Group (1986)Boys with late descending testes: the source of patients with‘‘retractile testes’’ undergoing orchidopexy. Br Med J 293:789–790

6. Goh DW, Hutson JM (1992) Is the retractile testis a normal,physiological variant or an anomaly that requires active treat-ment? Pediatr Surg Int 7:249

7. Hasen J, Boyar RM, Shapiro LR (1980) Gonadal function intrisomy 21. Hormone Res 12:345

8. Sakadamis A, Angelopoulou N, Matziari C, Papameletiou V,Souftas V (2002) Bone mass, gonadal function and biochemicalassessment in young men with trisomy 21. Eur J ObstetGynecol Reprod Biol 100:208–12

9. Hadziselimovic F, Herzog B, Seguchi H (1975) Surgical cor-rection of cryptorchidism at 2 years. Electron microscopic andmorphometric investigations. J Pediatr Surg 10:19–26

10. Zhou B, Hutson JM, Hasthorpe S (1998) Efficacy of orchido-pexy on spermatogenesis in the immature mutant ‘‘trans-scro-tal’’ rat as a cryptorchid model by quantitative cytologicalanalysis. Br J Urol 81:290–294

11. RabinowitzR, Hulbert WC (1997) Late presentation of crypt-orchidism: the etiology of testicular renascent. J Urol 157 (5):1892–1894

12. Dieckmann, KP, Rube C, Henke RP (1997) Association ofDown syndrome and testicular cancer. J Urol 157:1701–1704

13. Dexeus FH, Logothetis CJ, Chong C, Sella A, Ogden S (1988)Genetic abnormalities in men with germ cell tumors. J Urol140:80

14. Thornhill, JA, Conroy RM, Kelly GD, Walsh A, Fennelly JJ,Fitzpatrick JM (1988) An evaluation of predisposing factorsfor testis cancer in Ireland. Eur Urol 14:429

15. Hasen J, Boyar RM, Shapiro LR (1980) Gonadal function intrisomy 21. Horm Res 12:345–350

16. Johannisson R, Gropp A, Winking H, Coerdt W, Rehder H,Schwinger E (1983) Down’s syndrome in the male. Reproduc-tive pathology and meiotic studies. Hum Genet 63:132

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