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Is there an association between functional bladder outlet obstruction and Down's syndrome?
Journal of Pediatric Urology (2007) 3, 369e374
Is there an association between functional bladder outlet obstruction and Down’s syndrome? J.A. Hicks, C. Carson, P.S.J. Malone* Department of Paediatric Nephro-Urology, Southampton University Hospitals NHS Trust, Southampton, UK Received 14 December 2006; accepted 1 February 2007 Available online 10 April 2007
KEYWORDS Down’s Syndrome; Functional bladder outlet obstruction
Abstract Objective: The incidence of urinary tract abnormalities in patients with Down’s syndrome (DS) is estimated to be 3e7%. Abnormalities included are renal hypoplasia, renal cysts, ureterovesical and ureteropelvic junction obstruction and, more recently, an association between males with DS and the non-neurogenic neurogenic bladder has been reported. Based on clinical experience, the hypothesis is tested that patients with DS have functional bladder outflow obstruction secondary to detrusor sphincter dyssynergia. Methods: This study comprised three parts: an initial retrospective review of case notes of existing patients, followed by a prospective community-based study of all patients with DS to assess the incidence and types of bladder dysfunction, and a final hospital-based assessment where a problem was identified following return of the questionnaire. Results: The retrospective study identified a high potential for renal injury with three out of seven patients requiring urinary diversion for dilated upper tracts secondary to bladder outflow obstruction. The prospective study identified a high incidence (77%) of bladder dysfunction with 68% having a history of wetting. Conclusion: There is a potentially serious problem in children with DS that is not widely appreciated. We recommend that, at the very least, such children have a detailed history of bladder function taken, and where a problem is detected a urinary tract ultrasound scan should be performed. ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Down’s syndrome (DS) is a chromosomal disorder caused by an error in cell division that results in additional chromosome 21 material, trisomy 21. The prevalence of DS is 1/600 live births [1]. There is a spectrum of conditions associated with DS, the most prevalent being cardiac with * Corresponding author. Department of Paediatric NephroUrology, G Level, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Tel.: þ44 23 80796744; fax: þ44 23 80794008. E-mail address: [email protected] (P.S.J. Malone).
approximately 50% of children affected [1]. Other associations include ENT, orthopaedic, ophthalmic, endocrine, immunological, haematological, dermatological, neuropsychiatric and gastrointestinal, including achalasia of the oesophagus and Hirschsprung’s disease [1]. The incidence of urinary tract abnormalities in DS is 3e 7% [2], and this includes abnormalities of the upper urinary tracts such as renal hypoplasia [3], renal cysts [4], and ureterovesical and ureteropelvic junction obstruction [2]. Lower genitourinary anomalies are uncommon but include hypospadias [5] and PUV [6].
1477-5131/$30 ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2007.02.003
370 An association between males with DS and the nonneurogenic neurogenic bladder, a condition thought to be related to functional bladder outlet obstruction (BOO) secondary to detrusor sphincter dyssynergia (DSD) [7], has recently been reported [8]. DSD is a well-recognised phenomenon in children causing urinary incontinence and UTI, but with the potential to cause renal injury. There are several alternative names used to describe this condition, non-neurogenic neurogenic bladder [7], learned voiding dysfunction [8], dysfunctional elimination syndrome [8], elimination dyssynergia and an extreme form called the Hinman syndrome [9]. This study attempts to expand on the possible association between DSD and DS suggested by Barqawi et al. [8], in whose study only four males were retrospectively reviewed. The existence of BOO in children with DS may be masked because the symptoms are explained as delayed toilet training secondary to a learning disability. This may cause delay in making an important diagnosis and so the opportunity to avoid renal injury is missed.
Methods The study had local ethical approval. There were three parts to the study. The initial part was a retrospective casenote review of existing patients. The second part was a community-based postal questionnaire survey to assess the incidence of bladder dysfunction in the local population of children with DS. The third part of the study was a further hospital-based investigation of those children who identified bladder dysfunction in the questionnaire. The first part of the study involved children with DS diagnosed with bladder dysfunction in the Southampton Paediatric Urology Department between February 1988 and February 2004. We categorized the problem in terms of presentation, investigations, management and outcome. The second part involved children with DS, aged 5e 16 years and living in the Southampton area, who were identified using the Special Needs Module of the Community Child Health System database. All the families identified were sent a study pack. This included a letter of invitation from the investigators, a covering letter from their community paediatrician, the questionnaire and a prepaid envelope. The questionnaire had not been validated previously but attempted to identify urinary symptoms such as wetting, micturition symptoms and any episodes of UTI or any urinary problems that had previously been identified (Appendix A). After 1 month, non-responders were sent a reminder letter and another questionnaire. Finally, children identified with symptoms suggestive of BOO were invited to attend for further assessment. This included a full micturition history, history of bowel symptoms, examination, bladder scans pre and post voiding and a urine flow rate.
J.A. Hicks et al. a urinary problem was 3 years and 7 months (newborn to 9 years) with a mean follow up of 5 years and 8 months (7 months to 15 years). One patient presented following antenatal detection of hydronephrosis, four with UTI, and the final two patients presented with urinary incontinence and an associated weak urinary stream. Investigations included ultrasound (US) and cystourethroscopy in all and micturating cystourethrogram in six of the patients. Three patients had urodynamics and other investigations included IVU (Fig. 1), DMSA scan, and spinal and abdominal X-rays. Findings included bilateral hydroureteronephrosis in five and unilateral hydronephrosis with or without dilated ureters in two. Bladder wall thickening with incomplete bladder emptying was found in five patients. Three had bilateral VUR with some demonstrating DSD. Video-urodynamics demonstrated reduced functional capacity with decreased bladder compliance and detrusor overactivity in all three who underwent this investigation. Anatomical urethral obstruction and neuropathy were excluded in all patients. Three patients required urinary diversion, ureterostomy in one (later converted to a colonic conduit) and vesicostomy in two (later managed with an ileocystoplasty and Mitrofanoff procedure). Four improved through non-operative treatments.
Results Retrospective study There were seven patients in this part of the study, six males and one female. Their mean age at diagnosis with
Figure 1 (a) IVU of female patient presenting with UTI at 1 year of age. (b) IVU following bilateral ureterostomy.
Down’s and bladder outlet obstruction Table 1
371
Children who reported episodes of incontinence
Child
Age (years)
When?
Frequency
Severity
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
15 5 5 13 11 11 15 10 9 9 9 14 15 14 14
D D DþN N DþN D DþN DþN DþN D DþN DþN DþN DþN DþN
1e4/month 1e4/month 1e4/month 1e4/month 1e4/month 1e4/month N/A 1e4/month 1e4/month 1e4/month >2/day >2/day 1e4/month 1e4/month 1e4/month
Damp Visibly wet Soaked Soaked Visibly wet Damp N/A Damp Soaked Visibly wet Soaked Visibly wet Visibly wet Damp Soaked
D, day wetting only; N, night wetting only; D þ N, day and night wetting; N/A, not answered.
Of those four, two had urinary symptoms but little evidence of renal damage and are being closely followed, and two were successfully treated with alpha blockers.
Postal questionnaire Forty-two children met the inclusion criteria of which 22 responded (52%), nine females and 13 males. Seventeen patients (77%) reported some form of bladder dysfunction. Fifteen (68%) reported wetting problems, four day only, one night only and 10 day and night. All day wetters reported urge incontinence and four reported additional giggle incontinence. Twelve of the children had one to four episodes of incontinence per month, two reported more than twice per day and one did not answer this question (Table 1). Nine (41%), two of whom did not wet, reported problems with bladder emptying with at least one of the following symptoms: hesitancy, weak stream, straining, intermittency and urine retention (Table 2).
Table 2
Hospital visit and further assessment Only three of the 17 patients with bladder dysfunction agreed to attend for further assessment, two males (aged 14 and 15 years) and one female (14 years). All three had bladder scans pre and post voiding. The two males underwent urine flow rate measurement. All had complete bladder emptying and one demonstrated a staccato voiding pattern with a maximum flow rate of 12 ml/s suggestive of DSD.
Discussion Following a literature search we identified only one publication that reported an association between DS and non-neurogenic neurogenic bladder [8]. This was a small study that included only four patients, all of whom were male. In our retrospective review we identified seven patients with DS and probable DSD, a condition that could be labelled as non-neurogenic neurogenic bladder, thus supporting the findings of Barqawi et al. [8]. One important difference is that our study included one female alerting us to the fact that this problem is not limited to males. The potential for renal injury in these patients is high, with three out of the seven in our study requiring urinary diversion for dilated upper tracts, and three out of four in the other study [8] requiring surgical intervention for upper tract preservation. On the basis of these two studies, an association between DS and serious bladder dysfunction, probably secondary to DSD, has been identified. One study of the morbidity of isolated dysfunctional voiding syndrome in 37 children found significant morbidity in 40% of patients with the development of chronic irreversible renal disease requiring major urological surgery [10]. From this it is clear that functional BOO has the potential to cause significant renal injury. Functional BOO would appear to be a major health issue for patients with DS that should be identified and managed pre-emptively. This stimulated us to conduct the prospective community-based study to investigate the link between DS and functional BOO further. We were disappointed by the poor response rate to the questionnaire (52%), and accept that the results may be biased and not reflective of
Children with bladder-emptying symptoms
Child
Incontinence
Hesitancy
Weak flow
Strain
Intermittent flow
Retention
1 2 3 4 5 6 7 8 9 10 11
X X X
X
X X
X
X X X
X
X X X X X
X
X X X X X X
X, child reported symptoms.
X
X
372
J.A. Hicks et al.
the population of patients with DS as a whole. It would seem that the parents of patients with DS are highly protective and do not want to expose them to anything that could upset them. It is unlikely that the design of the questionnaire itself caused the poor response rate as it addressed the issues of urinary tract pathology in a very general way as seen in Appendix A. Despite this a high incidence of bladder dysfunction was identified (77%). Even if the study is biased and those who did not respond had no bladder dysfunction, there is still an incidence of problems in over 30% of the Down’s population representing a significant health-care issue. Sixty-eight percent of the children had a history of wetting and half of these had symptoms suggestive of BOO. For many of these patients wetting was a significant problem in itself, not to mention the potential the bladder dysfunction had to cause renal damage. Only two of these children had urinary investigations and thankfully these were normal. The community paediatricians are in the process of offering urinary tract US scans to the remaining patients. Objective investigations (flow rates and bladder scan) were performed in only three children and one was found to have an obstructive voiding pattern, but all three emptied their bladders to completion. While we accept that uroflowmetry is insufficient to diagnose BOO because it cannot distinguish obstruction from poor bladder contractility [11,12], we believe that when the prospective data are assessed in conjunction with the retrospective data, the most likely explanation is functional BOO, probably
secondary to DSD. If this hypothesis were to be proven, formal urodynamic and electromyography measurements would be required, but we do not believe this was possible in this study. Interestingly, DS has already been associated with the other sphincter in coordination disorders of Hirschsprung’s disease and achalasia of the oesophagus [1]. DSD had been thought to be an acquired condition that presented in school-age children; however, one study identified non-neurogenic neurogenic bladder in the neonatal period [13]. The mean age of diagnosis in our retrospective review was 3 years and 7 months; therefore, most of these children were pre-school. Given their age, it is unlikely that this is an acquired phenomenon, and it is most likely to be a form of congenital bladder dysfunction found more commonly in children with DS than in normal children. We accept that there are many drawbacks to this study and the evidence supporting the conclusions is circumstantial rather than objective. We believe the findings do identify a potentially serious problem in children with DS that is not widely appreciated, particularly by the paediatricians looking after them. At the very least, children with DS should always have a history of bladder function taken, and in those where a problem is detected an US scan of the urinary tract is indicated. This should allow the early detection of upper tract problems and hopefully, with appropriate treatment of the bladder, prevention of irreversible renal damage.
Appendix A
Questionnaire
Child’s Name:_______________________Date of Birth:_____________ Sex:_____________ Address:_____________________________________________________________ _____________________________________________________________________ _____________________________________________________________________ Yes No 1. Has your child ever suffered from a urinary tract infection? If no please go to question 2. If yes a. When? ____________________________________________ b. How often? ___________________________________________ c. Management? d. Investigations:
Home
Antibiotics Yes
Hospital No
i. Urine specimen ii. Ultrasound iii. X ray 2. Has your child ever suffered from accidental wetting? Yes No If no please go to question 3. If yes Yes No a. Night only? if yes please go to question 3 b. Day only?
if yes please go to question 2d
c. Day and night? d. Does wetting occur when i. Coughing? ii. Giggling? iii. When need toilet?
if yes please go to question 2d Yes
No
Down’s and bladder outlet obstruction
373
e. How often does wetting occur? i. More than once a week ii. 1-2 times/day iii. More than twice a day f. How severe is the wetting? i. Damp?
Outer clothing becomes
ii. Visibly wet? iii. Soaked through? Yes
g. Do you use protection against wetting? (e.g. Pads) if yes what do you use?
3. Has your child ever had any problems emptying their bladder?
Yes
No
No
a. How frequently does your child pass urine? i. 1-4 times/day ii. 5-8 times/day iii. 9+ times/day b. How long can they hold on if they need to pass urine? i. cannot hold on ii. 0-2 minutes iii. 2-10 minutes iv. 11-30 minutes v. 30+ minutes c. Has your child ever needed to pass urine but had difficulty starting?
d. Has your child ever had a weak urine flow?
Yes
No
Yes
No
Yes e. Has your child ever had to strain to pass urine? No f. Does yo ur child ever pass urine stop and then start passing urine again? Yes No g. At the end of passing urine does your child’s urine flow turn to a dribble? Yes No h. Has your child ever stopped passing urine for several days? Yes
No
i. Is your child under the care of any Paediatric Doctor? In the Co mm unity? Na me: Na me
4. Have you ever been told your child has any urinary problem s, kidney problems or bladder problems, such as when under investigation for some other reason at GP, hospital or other healthcare setting? Yes No if yes please give details
Thank you for reading and filling in this questionnaire
Version no 3 20/01/04
References [1] Dennis J, Marder E. Medical management of children with Down’s syndrome. Curr Paediatr 2001;11:57e63. [2] Doss B, Evans M, Feldman B, Jacques S, Johnson A, Johnson M, et al. Fetal obstructive uropathy in trisomy syndromes. Fetal Diagn Ther 2000;15:342e7.
[3] Kravtzora G, Lazjuk G, Lurie I. The malformations of the urinary system in autosomal disorders. Virchows Arch A Pathol Anat Histol 1975;368:167e78. [4] Ariel I, Wells T, Landing B, Singer D. The urinary system in Down syndrome: a study of 124 autopsy cases. Pediatr Pathol 1991;11:879e88.
374 [5] Dyke D, Heide F, Lang D, Lowe P. Hypospadias and urethral abnormalities in Down syndrome. Clin Pediatr (Philadelphia) 1987;26:40e2. [6] Mercer ES, Broecker B, Smith EA, Kirsh AJ, Scherz HC, Amassad C. Urological manifestations of Down’s syndrome. J Urol 2004;171:1250e3. [7] Crowley J, McAlister W. Lower genitourinary tract anomalies in a male with Down syndrome. Pediatr Radiol 1995; 25:377e8. [8] Barqawi A, Checa G, Furness P, Handel L. Koyle males with Down’s syndrome and nonneurogenic neurogenic bladder. J Urol 2003;169:646e9.
J.A. Hicks et al. [9] Hunt G, Whitaker R, Withycombe J. Intermittent catheterisation in the management of children with neuropathic bladder. Lancet 1978;ii:981e3. [10] Hinman F. Nonneurogenic neurogenic bladder (the Hinman syndrome) e 15 years later. J Urol 1986;136:769e77. [11] Mayo ME, Yang CC. Morbidity of dysfunctional voiding syndrome. Urology 1997;49:445e8. [12] Kelly C. Evaluation of voiding dysfunction and measurement of bladder volume. Rev Urol 2004;6:S32e7. [13] Jayanthi VR, Khoury AE, McLoire GA, Agarwal SK. The nonneurogenic neurogenic bladder of early infancy. J Urol 1997; 158:1281e5.
Is there an association between functional bladder outlet obstruction and Down’s syndrome? J.A. Hicks, C. Carson, P.S.J. Malone* Department of Paediatric Nephro-Urology, Southampton University Hospitals NHS Trust, Southampton, UK Received 14 December 2006; accepted 1 February 2007 Available online 10 April 2007
KEYWORDS Down’s Syndrome; Functional bladder outlet obstruction
Abstract Objective: The incidence of urinary tract abnormalities in patients with Down’s syndrome (DS) is estimated to be 3e7%. Abnormalities included are renal hypoplasia, renal cysts, ureterovesical and ureteropelvic junction obstruction and, more recently, an association between males with DS and the non-neurogenic neurogenic bladder has been reported. Based on clinical experience, the hypothesis is tested that patients with DS have functional bladder outflow obstruction secondary to detrusor sphincter dyssynergia. Methods: This study comprised three parts: an initial retrospective review of case notes of existing patients, followed by a prospective community-based study of all patients with DS to assess the incidence and types of bladder dysfunction, and a final hospital-based assessment where a problem was identified following return of the questionnaire. Results: The retrospective study identified a high potential for renal injury with three out of seven patients requiring urinary diversion for dilated upper tracts secondary to bladder outflow obstruction. The prospective study identified a high incidence (77%) of bladder dysfunction with 68% having a history of wetting. Conclusion: There is a potentially serious problem in children with DS that is not widely appreciated. We recommend that, at the very least, such children have a detailed history of bladder function taken, and where a problem is detected a urinary tract ultrasound scan should be performed. ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Down’s syndrome (DS) is a chromosomal disorder caused by an error in cell division that results in additional chromosome 21 material, trisomy 21. The prevalence of DS is 1/600 live births [1]. There is a spectrum of conditions associated with DS, the most prevalent being cardiac with * Corresponding author. Department of Paediatric NephroUrology, G Level, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Tel.: þ44 23 80796744; fax: þ44 23 80794008. E-mail address: [email protected] (P.S.J. Malone).
approximately 50% of children affected [1]. Other associations include ENT, orthopaedic, ophthalmic, endocrine, immunological, haematological, dermatological, neuropsychiatric and gastrointestinal, including achalasia of the oesophagus and Hirschsprung’s disease [1]. The incidence of urinary tract abnormalities in DS is 3e 7% [2], and this includes abnormalities of the upper urinary tracts such as renal hypoplasia [3], renal cysts [4], and ureterovesical and ureteropelvic junction obstruction [2]. Lower genitourinary anomalies are uncommon but include hypospadias [5] and PUV [6].
1477-5131/$30 ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2007.02.003
370 An association between males with DS and the nonneurogenic neurogenic bladder, a condition thought to be related to functional bladder outlet obstruction (BOO) secondary to detrusor sphincter dyssynergia (DSD) [7], has recently been reported [8]. DSD is a well-recognised phenomenon in children causing urinary incontinence and UTI, but with the potential to cause renal injury. There are several alternative names used to describe this condition, non-neurogenic neurogenic bladder [7], learned voiding dysfunction [8], dysfunctional elimination syndrome [8], elimination dyssynergia and an extreme form called the Hinman syndrome [9]. This study attempts to expand on the possible association between DSD and DS suggested by Barqawi et al. [8], in whose study only four males were retrospectively reviewed. The existence of BOO in children with DS may be masked because the symptoms are explained as delayed toilet training secondary to a learning disability. This may cause delay in making an important diagnosis and so the opportunity to avoid renal injury is missed.
Methods The study had local ethical approval. There were three parts to the study. The initial part was a retrospective casenote review of existing patients. The second part was a community-based postal questionnaire survey to assess the incidence of bladder dysfunction in the local population of children with DS. The third part of the study was a further hospital-based investigation of those children who identified bladder dysfunction in the questionnaire. The first part of the study involved children with DS diagnosed with bladder dysfunction in the Southampton Paediatric Urology Department between February 1988 and February 2004. We categorized the problem in terms of presentation, investigations, management and outcome. The second part involved children with DS, aged 5e 16 years and living in the Southampton area, who were identified using the Special Needs Module of the Community Child Health System database. All the families identified were sent a study pack. This included a letter of invitation from the investigators, a covering letter from their community paediatrician, the questionnaire and a prepaid envelope. The questionnaire had not been validated previously but attempted to identify urinary symptoms such as wetting, micturition symptoms and any episodes of UTI or any urinary problems that had previously been identified (Appendix A). After 1 month, non-responders were sent a reminder letter and another questionnaire. Finally, children identified with symptoms suggestive of BOO were invited to attend for further assessment. This included a full micturition history, history of bowel symptoms, examination, bladder scans pre and post voiding and a urine flow rate.
J.A. Hicks et al. a urinary problem was 3 years and 7 months (newborn to 9 years) with a mean follow up of 5 years and 8 months (7 months to 15 years). One patient presented following antenatal detection of hydronephrosis, four with UTI, and the final two patients presented with urinary incontinence and an associated weak urinary stream. Investigations included ultrasound (US) and cystourethroscopy in all and micturating cystourethrogram in six of the patients. Three patients had urodynamics and other investigations included IVU (Fig. 1), DMSA scan, and spinal and abdominal X-rays. Findings included bilateral hydroureteronephrosis in five and unilateral hydronephrosis with or without dilated ureters in two. Bladder wall thickening with incomplete bladder emptying was found in five patients. Three had bilateral VUR with some demonstrating DSD. Video-urodynamics demonstrated reduced functional capacity with decreased bladder compliance and detrusor overactivity in all three who underwent this investigation. Anatomical urethral obstruction and neuropathy were excluded in all patients. Three patients required urinary diversion, ureterostomy in one (later converted to a colonic conduit) and vesicostomy in two (later managed with an ileocystoplasty and Mitrofanoff procedure). Four improved through non-operative treatments.
Results Retrospective study There were seven patients in this part of the study, six males and one female. Their mean age at diagnosis with
Figure 1 (a) IVU of female patient presenting with UTI at 1 year of age. (b) IVU following bilateral ureterostomy.
Down’s and bladder outlet obstruction Table 1
371
Children who reported episodes of incontinence
Child
Age (years)
When?
Frequency
Severity
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
15 5 5 13 11 11 15 10 9 9 9 14 15 14 14
D D DþN N DþN D DþN DþN DþN D DþN DþN DþN DþN DþN
1e4/month 1e4/month 1e4/month 1e4/month 1e4/month 1e4/month N/A 1e4/month 1e4/month 1e4/month >2/day >2/day 1e4/month 1e4/month 1e4/month
Damp Visibly wet Soaked Soaked Visibly wet Damp N/A Damp Soaked Visibly wet Soaked Visibly wet Visibly wet Damp Soaked
D, day wetting only; N, night wetting only; D þ N, day and night wetting; N/A, not answered.
Of those four, two had urinary symptoms but little evidence of renal damage and are being closely followed, and two were successfully treated with alpha blockers.
Postal questionnaire Forty-two children met the inclusion criteria of which 22 responded (52%), nine females and 13 males. Seventeen patients (77%) reported some form of bladder dysfunction. Fifteen (68%) reported wetting problems, four day only, one night only and 10 day and night. All day wetters reported urge incontinence and four reported additional giggle incontinence. Twelve of the children had one to four episodes of incontinence per month, two reported more than twice per day and one did not answer this question (Table 1). Nine (41%), two of whom did not wet, reported problems with bladder emptying with at least one of the following symptoms: hesitancy, weak stream, straining, intermittency and urine retention (Table 2).
Table 2
Hospital visit and further assessment Only three of the 17 patients with bladder dysfunction agreed to attend for further assessment, two males (aged 14 and 15 years) and one female (14 years). All three had bladder scans pre and post voiding. The two males underwent urine flow rate measurement. All had complete bladder emptying and one demonstrated a staccato voiding pattern with a maximum flow rate of 12 ml/s suggestive of DSD.
Discussion Following a literature search we identified only one publication that reported an association between DS and non-neurogenic neurogenic bladder [8]. This was a small study that included only four patients, all of whom were male. In our retrospective review we identified seven patients with DS and probable DSD, a condition that could be labelled as non-neurogenic neurogenic bladder, thus supporting the findings of Barqawi et al. [8]. One important difference is that our study included one female alerting us to the fact that this problem is not limited to males. The potential for renal injury in these patients is high, with three out of the seven in our study requiring urinary diversion for dilated upper tracts, and three out of four in the other study [8] requiring surgical intervention for upper tract preservation. On the basis of these two studies, an association between DS and serious bladder dysfunction, probably secondary to DSD, has been identified. One study of the morbidity of isolated dysfunctional voiding syndrome in 37 children found significant morbidity in 40% of patients with the development of chronic irreversible renal disease requiring major urological surgery [10]. From this it is clear that functional BOO has the potential to cause significant renal injury. Functional BOO would appear to be a major health issue for patients with DS that should be identified and managed pre-emptively. This stimulated us to conduct the prospective community-based study to investigate the link between DS and functional BOO further. We were disappointed by the poor response rate to the questionnaire (52%), and accept that the results may be biased and not reflective of
Children with bladder-emptying symptoms
Child
Incontinence
Hesitancy
Weak flow
Strain
Intermittent flow
Retention
1 2 3 4 5 6 7 8 9 10 11
X X X
X
X X
X
X X X
X
X X X X X
X
X X X X X X
X, child reported symptoms.
X
X
372
J.A. Hicks et al.
the population of patients with DS as a whole. It would seem that the parents of patients with DS are highly protective and do not want to expose them to anything that could upset them. It is unlikely that the design of the questionnaire itself caused the poor response rate as it addressed the issues of urinary tract pathology in a very general way as seen in Appendix A. Despite this a high incidence of bladder dysfunction was identified (77%). Even if the study is biased and those who did not respond had no bladder dysfunction, there is still an incidence of problems in over 30% of the Down’s population representing a significant health-care issue. Sixty-eight percent of the children had a history of wetting and half of these had symptoms suggestive of BOO. For many of these patients wetting was a significant problem in itself, not to mention the potential the bladder dysfunction had to cause renal damage. Only two of these children had urinary investigations and thankfully these were normal. The community paediatricians are in the process of offering urinary tract US scans to the remaining patients. Objective investigations (flow rates and bladder scan) were performed in only three children and one was found to have an obstructive voiding pattern, but all three emptied their bladders to completion. While we accept that uroflowmetry is insufficient to diagnose BOO because it cannot distinguish obstruction from poor bladder contractility [11,12], we believe that when the prospective data are assessed in conjunction with the retrospective data, the most likely explanation is functional BOO, probably
secondary to DSD. If this hypothesis were to be proven, formal urodynamic and electromyography measurements would be required, but we do not believe this was possible in this study. Interestingly, DS has already been associated with the other sphincter in coordination disorders of Hirschsprung’s disease and achalasia of the oesophagus [1]. DSD had been thought to be an acquired condition that presented in school-age children; however, one study identified non-neurogenic neurogenic bladder in the neonatal period [13]. The mean age of diagnosis in our retrospective review was 3 years and 7 months; therefore, most of these children were pre-school. Given their age, it is unlikely that this is an acquired phenomenon, and it is most likely to be a form of congenital bladder dysfunction found more commonly in children with DS than in normal children. We accept that there are many drawbacks to this study and the evidence supporting the conclusions is circumstantial rather than objective. We believe the findings do identify a potentially serious problem in children with DS that is not widely appreciated, particularly by the paediatricians looking after them. At the very least, children with DS should always have a history of bladder function taken, and in those where a problem is detected an US scan of the urinary tract is indicated. This should allow the early detection of upper tract problems and hopefully, with appropriate treatment of the bladder, prevention of irreversible renal damage.
Appendix A
Questionnaire
Child’s Name:_______________________Date of Birth:_____________ Sex:_____________ Address:_____________________________________________________________ _____________________________________________________________________ _____________________________________________________________________ Yes No 1. Has your child ever suffered from a urinary tract infection? If no please go to question 2. If yes a. When? ____________________________________________ b. How often? ___________________________________________ c. Management? d. Investigations:
Home
Antibiotics Yes
Hospital No
i. Urine specimen ii. Ultrasound iii. X ray 2. Has your child ever suffered from accidental wetting? Yes No If no please go to question 3. If yes Yes No a. Night only? if yes please go to question 3 b. Day only?
if yes please go to question 2d
c. Day and night? d. Does wetting occur when i. Coughing? ii. Giggling? iii. When need toilet?
if yes please go to question 2d Yes
No
Down’s and bladder outlet obstruction
373
e. How often does wetting occur? i. More than once a week ii. 1-2 times/day iii. More than twice a day f. How severe is the wetting? i. Damp?
Outer clothing becomes
ii. Visibly wet? iii. Soaked through? Yes
g. Do you use protection against wetting? (e.g. Pads) if yes what do you use?
3. Has your child ever had any problems emptying their bladder?
Yes
No
No
a. How frequently does your child pass urine? i. 1-4 times/day ii. 5-8 times/day iii. 9+ times/day b. How long can they hold on if they need to pass urine? i. cannot hold on ii. 0-2 minutes iii. 2-10 minutes iv. 11-30 minutes v. 30+ minutes c. Has your child ever needed to pass urine but had difficulty starting?
d. Has your child ever had a weak urine flow?
Yes
No
Yes
No
Yes e. Has your child ever had to strain to pass urine? No f. Does yo ur child ever pass urine stop and then start passing urine again? Yes No g. At the end of passing urine does your child’s urine flow turn to a dribble? Yes No h. Has your child ever stopped passing urine for several days? Yes
No
i. Is your child under the care of any Paediatric Doctor? In the Co mm unity? Na me: Na me
4. Have you ever been told your child has any urinary problem s, kidney problems or bladder problems, such as when under investigation for some other reason at GP, hospital or other healthcare setting? Yes No if yes please give details
Thank you for reading and filling in this questionnaire
Version no 3 20/01/04
References [1] Dennis J, Marder E. Medical management of children with Down’s syndrome. Curr Paediatr 2001;11:57e63. [2] Doss B, Evans M, Feldman B, Jacques S, Johnson A, Johnson M, et al. Fetal obstructive uropathy in trisomy syndromes. Fetal Diagn Ther 2000;15:342e7.
[3] Kravtzora G, Lazjuk G, Lurie I. The malformations of the urinary system in autosomal disorders. Virchows Arch A Pathol Anat Histol 1975;368:167e78. [4] Ariel I, Wells T, Landing B, Singer D. The urinary system in Down syndrome: a study of 124 autopsy cases. Pediatr Pathol 1991;11:879e88.
374 [5] Dyke D, Heide F, Lang D, Lowe P. Hypospadias and urethral abnormalities in Down syndrome. Clin Pediatr (Philadelphia) 1987;26:40e2. [6] Mercer ES, Broecker B, Smith EA, Kirsh AJ, Scherz HC, Amassad C. Urological manifestations of Down’s syndrome. J Urol 2004;171:1250e3. [7] Crowley J, McAlister W. Lower genitourinary tract anomalies in a male with Down syndrome. Pediatr Radiol 1995; 25:377e8. [8] Barqawi A, Checa G, Furness P, Handel L. Koyle males with Down’s syndrome and nonneurogenic neurogenic bladder. J Urol 2003;169:646e9.
J.A. Hicks et al. [9] Hunt G, Whitaker R, Withycombe J. Intermittent catheterisation in the management of children with neuropathic bladder. Lancet 1978;ii:981e3. [10] Hinman F. Nonneurogenic neurogenic bladder (the Hinman syndrome) e 15 years later. J Urol 1986;136:769e77. [11] Mayo ME, Yang CC. Morbidity of dysfunctional voiding syndrome. Urology 1997;49:445e8. [12] Kelly C. Evaluation of voiding dysfunction and measurement of bladder volume. Rev Urol 2004;6:S32e7. [13] Jayanthi VR, Khoury AE, McLoire GA, Agarwal SK. The nonneurogenic neurogenic bladder of early infancy. J Urol 1997; 158:1281e5.