Elimination disorders in persons with Prader-Willi and Fragile-X syndromes

Neurourology and Urodynamics 32:986–992 (2013)

Elimination Disorders in Persons With Prader–Williand Fragile-X Syndromes

Monika Equit,1* Aline Piro-Hussong,1 Justine Niemczyk,1 Leopold Curfs,2 and Alexander von Gontard11Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany

2Department of Clinical Genetics, Academic Hospital/University Maastricht—Governor Kremers Centre, Maastricht,The Netherlands

Aims: Elimination disorders are common in typically developing children. Only few studies have addressed elimina-tion disorders in persons with intellectual disability (ID)—and even fewer studies in those with specific syndromes.The aim of the study was to investigate the rates of elimination disorders and behavioral symptoms in persons withPrader–Willi (PWS) and Fragile-X syndromes (FXS) in a large sample. Methods: Three hundred fifty-seven personswith PWS or FXS were recruited through parent self-help groups. A questionnaire regarding elimination symptoms, aswell as the child behavior checklist (CBCL)/young adult behavior checklist (YABCL) were filled out by parents or care-givers. Results: The sample included 191 persons with PWS (54.5% male) with a mean age of 20.0 years and 166persons with FXS (92.2% male) with a mean age of 15.4 years. Persons with FXS were significantly more often affectedby elimination disorders. 29.3% of persons with PWS and 48.8% of persons with FXS had at least one eliminationdisorder. Persons with FXS also had more often DUI (29.5% vs. 12.0%) and FI (28.9% vs. 12.6%). Rates of NE weresimilar in both groups (22.0% in PWS vs. 28.9% in FXS). Young adults with PWS had more behavioral symptoms in theclinical range (70.8% vs. 48.3%). Incontinence and behavioral symptoms were significantly associated in persons withFXS. Conclusions: NE, DUI, and FI are very common in persons with FXS and PWS and are associated with otherbehavioral symptoms in persons with FXS. They persist into adulthood. Early assessment and treatment are recom-mended. Neurourol. Urodynam. 32:986–992, 2013. � 2012 Wiley Periodicals, Inc.

Key words: daytime urinary incontinence; fecal incontinence; fragile-X syndrome; intellectual disability; nocturnalenuresis; Prader–Willi syndrome

INTRODUCTION

Nocturnal enuresis (NE), daytime urinary incontinence(DUI), and faecal incontinence (FI) are common in typically de-veloping children: 10% of 7 year olds wet at night and 2–3%during the day, and 1–3% soil.1 Children with intellectual dis-ability (ID) have markedly higher rates of incontinence. In thelargest population-based study to date, 38% of 7-year-old chil-dren with ID had NE, 39% DUI, and 31% FI.2 Even young adultswith ID at the age of 20 years are still highly affected: 20%had NE, 20% DUI, and 19% FI. Also, incontinence is inverselyrelated to IQ; that is, the lower the IQ is, the more likely willincontinence occur.2

ID, formerly known as mental retardation, is defined by anIQ of under 70.3,4 ID comprises a heterogeneous group of ge-netic and neurodevelopmental disorders with mainly prenatalorigin.5 With the development of molecular genetic techni-ques, such as high-resolution micro-arrays, the aetiology ofmost cases of ID can be identified.5 Two of the most importantgenetic neurodevelopmental disorders are Prader–Willi (PWS)and Fragile-X syndromes (FXS).

With a prevalence of 1:10,000–1:14,000, PWS is caused by apaternal deletion on chromosome (15q11–13) in 70% of cases,by maternal disomy in 29% and by imprinting defects in 1%.6

The phenotype of PWS is characterized by hypogonadism,short stature, and obesity. Hypotonia and feeding problems ininfancy, hyperphagia, temper outbursts, affective disorders,stereotypies, and speech abnormalities are typical behavioralfeatures. IQ is reduced, mostly in the range of mild ID (IQ: 50–70). Incontinence had previously been reported anecdotally.7–9 In the first systematic study of 118 persons with PWS at amean age of 15.1 years, 13.6% had NE, 3.8% additional DUI,

and 3.3% FI. Lower urinary tract symptoms (LUTS) werecommon.10

FXS is the second most common genetic cause of ID (follow-ing Down syndrome) with a prevalence of 1:4,000. In mostcases, full mutation FXS is caused by an increase of CGG-trip-let repeats in the FMR-1 gene on the X-chromosome (Xq27.3)in the range of 200–2,000 (normal: 5–50, premutation: 50–200).11 The gene is then methylated and the expression of theFMR-protein inhibited. Large ears, a long face, and macroorch-idism are typical dysmorphic signs in boys with a full muta-tion. Behaviorally, attention-deficit/hyperactivity disorder(ADHD), social anxiety, autism spectrum and speech, and lan-guage disorders are typical.11–13 The intelligence quotient (IQ)was in the range of moderate ID (IQ: 35–50).12 Incontinencehas been reported recently in one case report of a 6-year-oldgirl14 and in a series of 49 boys with a mean age of 8.6 years,

Abbreviations used: CBCL, child behavior checklist; DUI, daytime urinaryincontinence; FI, faecal incontinence; FXS, fragile-X syndrome; ICD-10,international classification of diseases; ID, intellectual disability; IQ,intelligence quotient; LUTS, lower urinary tract symptoms; NE, nocturnalenuresis; PWS, Prader–Willi syndrome; UTI, urinary tract infection; YABCL,young adult behavior checklist.Conflict of interest: none.Christopher Chapple led the peer-review process as the Associate Editor responsi-ble for the paper.*Correspondence to: Monika Equit, PhD, Department of Child and AdolescentPsychiatry, Saarland University Hospital, Homburg 66421, Germany.E-mail: [email protected] 9 August 2012; Accepted 29 October 2012Published online 12 December 2012 in Wiley Online Library

(wileyonlinelibrary.com).

DOI 10.1002/nau.22352

� 2012 Wiley Periodicals, Inc.

of whom 27% had NE and/or DUI and 20% FI.12 Gabis et al.15

reported prevalence rates of 40.9% for NE and 36.4% for FI in22 children and adolescents/adults with FXS. For children upto the age of 12 years the prevalence of elimination disorderswas significantly higher than in adolescents (>12 years).

The aim of this study was to assess and compare the ratesand types of incontinence, as well as associated behavioralsymptoms in a large sample of persons with PWS and FXS.

Following exploratory questions and hypotheses wereinvestigated:

(1) How common are different types of incontinence in per-sons with PWS and FXS?

(2) Which associated LUTS are typical?(3) How common are behavioral problems in persons with

PWS and FXS?

Also, it was hypothesized that:

(1) Persons with FXS are more affected by incontinence thanpersons with PWS.

(2) Rates of incontinence in persons with FXS/PWS are highand persist into adulthood.

(3) Incontinence is associated with behavioral problems inboth PWS and FXS.

MATERIALS AND METHODS

Three hundred fifty-seven persons with PWS or FXS wererecruited through parent self-help groups. The study was ap-proved by the local ethics committee. Seven hundred forty-nine parents (350 FXS, 399 PWS) were sent two questionnairesto by mail. The return rate was 49.1% (172) from parents ofpersons with FXS and 48.9% (195) from parents of personswith PWS. The non-responders were not contacted. Reasons forlack or participation were change of address, decease of per-sons in the address files of the self-help groups and arrival ofquestionnaires after data entry. Four children did not fulfill the

inclusion criteria (age > 4 years) and six questionnaires couldnot be evaluated due to high missing values/arrival after endof data analysis. In total, 166 questionnaires of persons withFXS (47.4%) and 191 of those with PWS (47.9%) were analyzed.Parents were asked to fill out the ‘‘Parental Question-

naire: Enuresis/Urinary Incontinence.’’1,16 This is a widelyused questionnaire which includes 57 items referring today- and night-time wetting, toilet habits, observable void-ing behaviors and reactions, urinary tract infections, andstool habits which are rated in a yes/no format. Additionaldata (such as voiding and wetting frequency) are noted nu-merically. It has been used previously in a study on chil-dren with Spinal Muscular Atrophy and PWS.10,17 Broaddescriptive groups were formed: NE, DUI, and FI in total, aswell as isolated and combined groups.For children and adolescents (ages: 4–18 years) the child be-

havior checklist (CBCL) was used to assess behavioral symp-toms.18 This consists of 113 problem items, graded on a three-point scale. German norms were used.19 t-Values for the total,internalizing and externalizing scales were calculated. A clini-cal cut-off was defined by the 90th percentile (t-value 63).For adults, the young adult behavior scale (YABCL)20 with

107 items, which was developed for young adults aged 18–30years, was used with US American norms. Scales, t-values, andclinical cut-offs are the same as in the CBCL. As no comparablequestionnaire exists for the age of over 30 years, the YABCLwas used for all adults.Statistical analyses were performed with the PASW statis-

tics version 18 using descriptive statistics and frequencies forsample description. Hypotheses were tested with x2-tests,Fisher’s exact test, Student’s t-tests, and Welch-tests. A P-valueof 0.05 or less was taken as significance level.

RESULTS

The sample consisted of a total of 357 persons, 191 withPWS, and 166 with FXS. The mean age of the total group was17.9 (SD 9.5) years, for the PWS group 20.0 (SD 10.5), and for

TABLE I. Comparison of Frequencies of Elimination Disorders and Behavioral Problems in Persons With PWS and FXS

Total N (%) PWS N (%) FXS N (%) x2 (df ¼ 1)/t, P

357 (100) 191 (100) 166 (100)

At least one elimination disorder 137 (39.8) 56 (29.3) 81 (48.8) 13.88, <0.000

NE totala 90 (25.9) 42 (22.0) 48 (28.9) n.s.

NE isolated 34 (9.5) 21 (11.0) 13 (7.8) n.s.

DUI totala 72 (20.2) 23 (12.0) 49 (29.5) 15.96, <0.000

DUI isolated 15 (4.2) 5 (2.6) 10 (6.0) 4.56, 0.033

NE þ DUI combined 16 (4.5) 6 (3.1) 10 (6.0) n.s.

FI totala 72 (20.2) 24 (12.6) 48 (28.9) 14.19, <0.000

FI isolated 18 (5.0) 4 (2.1) 14 (8.4) 10.43, 0.001

FI þ NE combined 13 (3.6) 8 (4.2) 5 (3.0) n.s.

FI þ DUI combined 14 (3.9) 5 (2.6) 9 (5.4) n.s.

FI þ NE þ DUI combined 27 (7.6) 7 (3.7) 20 (12.0) 12.25, <0.000

CBCL total score: mean t-values (SD) 66.0 (8.2) 65.7 (8.8) 66.4 (7.6) n.s.b

CBCL internalizing score: mean t-values (SD) 60.8 (9.1) 59.8 (9.0) 61.7 (9.2) n.s.

CBCL externalizing score: mean t-values (SD) 59.4 (8.9) 60.3 (9.8) 58.5 (8.0) n.s.b

CBCL total score in clinical range (>90. percentile) (%) 59.3 (124) 59.4 (60) 59.3 (64) n.s.

YABCL total score: mean t-values (SD) 65.8 (4.9) 66.4 (5.1) 64.9 (4.4) n.s.

YABCL internalizing score: mean t-values (SD) 57.1 (8.5) 56.4 (8.3) 58.3 (8.8) n.s.

YABCL externalizing score: mean t-values (SD) 58.4 (7.0) 60.4 (6.4) 55.14 (6.8) �4.69, <0.000

YABCL total score in clinical range (>90 percentile; %) 61.9 (91) 70.8 (63) 48.3 (28) 6.86, 0.009

Only P values <0.05 are shown.aThese categories include all combinations of NE (NE isolated, NE þ DUI, FI þ NE, FI þ NE þ DUI), DUI (DUI isolated, NE þ DUI, FI þ DUI, FI þ NE þ DUI)

or FI (FI isolated, FI þ NE, FI þ DUI, FI þ NE þ DUI).bWelch-test (due to variance inhomogenity).

Incontinence in Prader–Willi/Fragile-X 987

Neurourology and Urodynamics DOI 10.1002/nau

the FXS group 15.4 (SD 7.4) years with a range from 4 to52 years. Persons with PWS were significantly older than per-sons with FXS (t ¼ �4.84; P < 0.000). Males were overrepre-sented in the FXS group (92.2% vs. 54.5%; x2(1) ¼ 62.66;P < 0.000). Most questionnaires were completed by parents(98.2% of FXS; 98.3% of PWS). 87.3% (145) of the persons withFXS lived at home and 9.6% (16) in institutional care, whereasonly 63.4% (121) of persons with PWS lived at home and33.5% (64) in institutional care (x2(1) ¼ 29.44; P < 0.000). Thegroups of persons with FXS or PWS were differentiated intofour different age groups: children (4–12 years), teens (13–17years), young adults (18–30 years), adults (>30 years). Withinthese age groups significant differences for living setting were

found only for young adults. 80.8% (42) of young adults withFXS but only 36.7% (22) of young adults with PWS lived athome (x2(1) ¼ 24.36; P < 0.000).The rate of incontinence was high in both groups with sig-

nificant differences (Table I). 29.3% of persons with PWS andeven 48.8% of persons with FXS had at least one eliminationdisorder. NE was the most common type in 25.9% of cases,20.2% of all persons were affected by DUI and FI with signifi-cantly higher rates of DUI (29.5% vs. 12.0%) and FI (28.9% vs.12.6%) in the FXS group.Although there was a decline over the age groups, inconti-

nence remains a common problem well into adulthood, asshown in Table II: 54.1% of children, 37.9% of teens, 25.9% of

TABLE II. Elimination Disorders in Different Age Groups From Child- to Adulthood: Comparison Between Persons With PWS and FXS

Total N (%) PWS N (%) FXS N (%) x2 (df ¼ 1), P

Child: 4–12 years 122 (100) 54 (100) 68 (100)

At least one elimination disorder 66 (54.1) 18 (33.3) 48 (70.6) 16.4, <0.000

NE totala 48 (39.3) 15 (27.8) 33 (48.5) 5.09, 0.024

NE isolated 11 (9.0) 5 (9.3) 6 (8.8) n.s.b

DUI totala 40 (32.8) 8 (14.8) 32 (47.1) 13.75, <0.000

Isolated 8 (6.6) 2 (3.7) 6 (8.8) n.s.b

NE þ DUI combined 11 (9.0) 2 (3.7) 9 (13.2) —, (0.007)b

FI totala 38 (31.1) 10 (18.5) 28 (41.2) 7.50, 0.006

Isolated 8 (6.6) 2 (3.7) 6 (8.8) n.s.b

FI þ NE combined 9 (7.4) 4 (7.4) 5 (7.4) n.s.b

FI þ DUI combined 4 (3.3) — 4 (5.9) —, 0.021b

FI þ NE þ DUI combined 17 (13.9) 4 (7.4) 13 (19.1) —, 0.005b

Teen: 13–17 years 87 (100) 47 (100) 40 (100)

At least one elimination disorder 33 (37.9) 16 (34.0) 17 (42.5) n.s.

NE totala 20 (23.0) 13 (27.7) 7 (17.5) n.s.

NE isolated 11 (12.6) 7 (14.9) 4 (10.0) n.s.b

DUI totala 17 (19.5) 8 (17.0) 9 (22.5) n.s.

Isolated 4 (4.6) 1 (2.1) 3 (7.5) n.s.b

NE þ DUI combined 3 (3.4) 3 (6.4) — n.s.b

FI totala 15 (17.2) 5 (10.6) 10 (25.0) n.s.

Isolated 4 (4.6) — 4 (10.0) —, 0.041b

FI þ NE combined 1 (1.1) 1 (2.1) — n.s.b

FI þ DUI combined 5 (5.7) 2 (4.3) 3 (7.5) n.s.b

FI þ NE þ DUI combined 5 (5.7) 2 (4.3) 3 (7.5) n.s.b

Young adult: 18–30 years 112 (100) 60 (100) 52 (100)

At least one elimination disorder 29 (25.9) 15 (25.0) 14 (26.9) n.s.

NE totala 18 (16.1) 10 (16.7) 8 (15.4) n.s.

NE isolated 9 (8.0) 6 (10.0) 3 (5.8) n.s.b

DUI totala 14 (12.5) 6 (10.0) 8 (15.4) n.s.

Isolated 2 (1.8) 1 (1.7) 1 (1.9) n.s.b

NE þ DUI combined 2 (1.8) 1 (1.7) 1 (1.9) n.s.b

FI totala 16 (14.3) 7 (11.7) 9 (17.3) n.s.

Isolated 4 (3.6) 1 (1.7) 3 (5.8) n.s.b


FI þ DUI combined 5 (4.5) 3 (5.0) 2 (3.8) n.s.b

FI þ NE þ DUI combined 5 (4.5) 1 (1.7) 4 (7.7) n.s.b

Adult: I30 years 35 (100) 29 (100) 6 (100)

At least one elimination disorder 7 (20.0) 6 (20.7) 1 (16.7) n.s.b

NE totala 4 (11.4) 4 (13.8) — n.s.b

NE isolated 3 (8.6) 3 (10.3) — n.s.b

DUI totala 1 (2.9) 1 (3.4) — n.s.b

Isolated 1 (2.9) 1 (3.4) — n.s.b

NE þ DUI combined — — — —

FI totala 3 (8.6) 2 (6.9) 1 (16.7) n.s.b

Isolated 2 (5.7) 1 (3.4) 1 (16.7) n.s.b


FI þ DUI combined — — — —

FI þ NE þ DUI combined — — — —

Only P values <0.05 are shown.aThese categories include all combinations of NE (NE isolated, NE þ DUI, FI þ NE, FI þ NE þ DUI), DUI (DUI isolated, NE þ DUI, FI þ DUI, FI þ NE þ DUI)

or FI (FI isolated, FI þ NE, FI þ DUI, FI þ NE þ DUI).bFisher exact test.

988 Equit et al.


young adults, and 20.0% of adults had at least one eliminationdisorder. At every age, persons with FXS were more affectedthan those with PWS. In childhood, the differences are highlysignificant for NE, DUI, and FI—and the majority of childrenwith FXS (70.6%) had at least one elimination disorder (vs.33.3% of children with PWS).

Also, 59% of children and adolescents (aged: 4–17; 11 years)with PWS/FXS had clinically relevant behavioral symptomsaccording to the CBCL without significant differences betweenthe two groups. This is six times higher than in the normativepopulation (norms: 10%). According to YABCL, 70.8% of adultswith PWS, and 48.3% of adults with FXS had clinically relevantbehavioral symptoms. At that age group, PWS persons weresignificantly more affected by behavioral problems in generaland by externalizing symptoms (Table I). There were no signifi-cant sex differences (neither in elimination disorders nor in

behavioral symptoms) in the PWS and the FXS groups (datanot shown). However, only 13 females with FXS wereincluded.For the entire sample of children, adolescents, and adults

(CBCL and YABCL combined), 66.2% (51/77) of persons withFXS, who had an elimination disorder, also had clinically rele-vant behavioral problems (x2(1) ¼ 5.58; P < 0.018), whereas nosignificant association between elimination disorder and be-havioral symptoms were found for persons with PWS (37/56).Micturition and bowel habits are presented in Table III.

There were some signs of LUTS, especially in persons withFXS: they had to rush to toilet immediately (41.0%), showedholding maneuvers (39.8%) and postponement (34.9%) moreoften than those with PWS. Also, they took less time withvoiding. Despite more LUTS, FXS persons had significantly lessurinary tract infections (UTIs). On the other hand, many

TABLE III. Micturition and Bowel Habits: Comparison Between Persons With PWS and FXS

Total N (%) PWS N (%) FXS N (%) x2 (df), P

357 (100) 191 (100) 166 (100)

Micturition habitsNumber of spontaneous voidings/day (n ¼ 284; missing values ¼ 73)

Not at all—3� 48 (13.4) 24 (12.6) 24 (14.5) n.s.a

4–8� 216 (60.5) 111 (58.1) 105 (63.3)

>8� 18 (5.0) 8 (4.2) 10 (6.0)

Don’t know 2 (0.6) — 2 (1.2)

Interval between micturitions (hr; n ¼ 252; missing values ¼ 105)

Not at all—less than once every 5 hr 15 (4.2) 10 (5.2) 5 (3.0) n.s.a

Every 3–5 hr 129 (36.1) 71 (37.2) 58 (34.9)

Every 1–2 hr 99 (27.7) 48 (25.1) 51 (30.7)

Several times/hour 5 (1.4) 2 (1.0) 3 (1.8)

Don’t know 4 (1.1) 1 (0.5) 3 (1.8)

Has to be sent to the toilet 72 (20.2) 28 (14.7) 44 (26.5) 8.16 (1), 0.004

Straining 22 (6.2) 13 (6.8) 9 (5.4) n.s.

Interrupted stream 39 (10.9) 26 (13.6) 13 (7.8) n.s.

Takes enough time for voiding 279 (78.2) 164 (85.9) 115 (69.3) 17.95 (1), 0.001

Urgency 93 (26.1) 49 (25.7) 44 (26.5) n.s.

Has to rush to toilet immediately 120 (33.6) 52 (27.2) 68 (41.0) 7.32 (1), 0.007

Uses holding maneuvers 104 (29.1) 38 (19.9) 66 (39.8) 17.16 (1), 0.001

Postponement 92 (25.8) 34 (17.8) 58 (34.9) 13.29 (1), 0.001

Previous UTIs 60 (16.8) 42 (22.0) 18 (10.8) 7.97 (1), 0.005

Fluid intake (n ¼ 332; missing values ¼ 25)

1/2–1 L 72 (20.2) 40 (20.9) 32 (19.3) n.s.

1.1–1.5 L 107 (30.0) 59 (30.9) 48 (28.9)

1.6–2 L 90 (25.2) 50 (26.2) 40 (24.1)

>2 L 63 (17.6) 29 (15.2) 34 (20.5)

Bowel habitsBowel movements (days/week; n ¼ 326; missing values ¼ 31)

1–2 days 4 (1.1) 3 (1.6) 1 (0.6) n.s.a

3–4 days 16 (4.5) 9 (4.7) 7 (4.2)

Daily 306 (85.7) 159 (83.2) 147 (88.6)

Bowel movements/day (n ¼ 317; missing values ¼ 40)

1� 235 (65.8) 128 (67.0) 107 (64.5) n.s.

2� 39 (10.9) 17 (8.9) 22 (13.3)

>2� 43 (12.0) 21 (11.0) 22 (13.3)

Stool consistency (n ¼ 302; missing values ¼ 55)

Hard 26 (7.3) 15 (7.9) 11 (6.6) n.s.a

Soft 171 (47.9) 94 (49.2) 77 (46.4)

Watery 1 (0.3) — 1 (0.6)

Variable 98 (27.5) 52 (27.2) 46 (27.7)

With blood 1 (0.3) 1 (0.5) —

Pain during defecation 5 (1.4) 2 (1.0) 3 (1.8) n.s.a

Abdominal pain 17 (4.8) 11 (5.8) 6 (3.6) n.s.

Cleans himself/herself sufficiently 135 (37.8) 96 (50.3) 39 (23.5) 34.01 (1), 0.001

Only P values <0.05 are shown.

Frequencies do not add up to total frequencies due to missing values.aFisher’s exact test.



micturition habits did not differ between the groups. On thewhole, micturition frequency was in the normal range: 60.5%voided 4–8 times/day. Only 13.4% went to the toilet less than3 times/day, which could be a sign of postponement and only5.0% had a high frequency of over 8 voidings/day. Fluid intakeseemed fairly adequate: only 20.2% drank a reduced volumeof 1/2 to 1 L/day. Also, constipation did not seem to be a ma-jor problem: 85.7% had daily bowel movements of averagesize and consistency. Persons with PWS had significantly moreproblems to clean themselves sufficiently after toileting(50.3% vs. 23.5%).

Information on specific aspects of NE, DUI, and FI are pre-sented in Tables IV and V. Persons with PWS or FXS with NE.48.9% had been dry before and the relapse was most commonin preschool age (up to the age of 6 years). 32.2% wetted everynight, 52.2% once a week or more. Especially persons withPWS were difficult to wake (Table IV).

No significant differences in specific aspects of DUI werefound between persons with FXS and persons with PWS.

Again, the majority had experienced a relapse up to the age of6 years. 15.3% of the entire sample wetted every day and halfat least once/week. 65.3% were incontinent once or twice/day(Table IV).Significantly more persons with FXS (48) had FI than those

with PWS (n ¼ 24; Table I). 50.7% of the entire group had beencontinent before, 76.7% soiled during the day—especially per-sons with FXS on a daily basis. In contrast, significantly morepersons with PWS (40.0%) soiled at night—and most of themnightly or at 3–4 nights/week (46.2%). In 53.4% of the entiregroup, stool sizes were large, and soft (Table V).

DISCUSSION

This is the largest systematic report on urinary incontinencein two discrete syndromes with ID. Incontinence is a verycommon problem: 1/2 of persons with FXS and 1/3 of thosewith PWS had at least one elimination disorder. Not just chil-dren, but also adolescents and adults are affected.

TABLE IV. Symptoms in the Subgroup of Persons With PWS and FXS With Any NE (Total NE; n ¼ 90; age � 5 years) and in the Subgroup of Persons WithPWS and FXS With Any DUI (Total DUI; n ¼ 72, age � 5 years)


Subgroup NE 90 (100) 42 (100) 48 (100)

Been dry before (night) 44 (48.9) 20 (47.6) 24 (50.0) n.s.

Dry at age (n ¼ 37; missing values ¼ 7)

0–4 years 7 (15.9) 6 (30.0) 1 (4.2) n.s.a

5–6 years 12 (27.3) 4 (20.0) 9 (33.3)

7–10 years 10 (22.7) 5 (25.0) 5 (20.8)

11–15 years 3 (6.8) 1 (5.0) 2 (8.3)

16–18 years 5 (11.5) 3 (15.0) 2 (8.3)

Wetness of bed (n ¼ 57; missing values ¼ 33)

Bed usually damp 15 (16.7) 7 (16.7) 8 (16.7) n.s.

Bed usually wet 29 (32.2) 16 (38.1) 13 (27.1)

Bed variable 13 (14.4) 6 (14.3) 7 (14.6)

Number of wet nights/week (n ¼ 79; missing values ¼ 11)

Every night 29 (32.2) 14 (33.3) 15 (31.3) n.s.

3–4�/week 11 (12.2) 7 (16.7) 4 (8.3)

1–2�/week 7 (7.8) 3 (7.1) 4 (8.3)

1–2�/month 13 (14.4) 6 (14.3) 7 (14.6)

Less than 1�/month 19 (21.1) 6 (14.3) 13 (27.1)

Wakes up after wetting 32 (35.6) 14 (33.3) 18 (37.5) n.s.

Deep sleeper 25 (27.8) 20 (47.6) 5 (10.4) 15.65 (1), 0.000

Relatives affected in urinary incontinence 13 (14.4) 6 (14.3) 7 (14.6) n.s.

Subgroup DUI 72 (100) 23 (100) 49 (100)

Been dry before (day) 49 (68.1) 20 (87.0) 29 (59.2) 4.79 (1), 0.029

Dry at age (n ¼ 44; missing values ¼ 5)

0–4 years 18 (36.7) 11 (55.0) 7 (24.1) n.s.a

5–6 years 14 (28.6) 3 (15.0) 11 (37.9)

7–10 years 11 (22.4) 4 (20.0) 7 (24.1)

11–15 years 1 (2.0) 1 (5.0) —

Number of wet days/week (n ¼ 68; missing values ¼ 4)

Every day 11 (15.3) 2 (8.7) 9 (18.4) n.s.

3–4�/week 11 (15.3) 1 (4.3) 10 (20.4)

1–2�/week 12 (16.7) 3 (13.0) 9 (18.4)

1–2�/month 14 (19.4) 6 (26.1) 8 (16.3)

Less than 1�/month 20 (27.8) 10 (43.5) 10 (20.4)

Number of incontinence episodes/day (n ¼ 61; missing values ¼ 11)

1–2�/day 47 (65.3) 15 (65.2) 32 (65.3) n.s.a

3–4�/day 8 (11.1) 1 (4.3) 7 (14.3)

5–6�/day 5 (6.9) 2 (8.7) 3 (6.1)

More than 6�/day 1 (1.4) — 1 (2.0)



990 Equit et al.


The high rate of incontinence in children with FXS could bedue to common comorbid externalizing disorders (such asADHD and ODD), associated with low compliance and highparental stress.12,21 Thus, only in FXS were behavior and in-continence correlated—not in PWS.

Also, ID on the average, is lower in persons with FXS. Popu-lation-based rates for persons with moderate ID (IQ: 35–50;comparable to FXS) for the ages 7 (and 20) years were 44.1%(17.6%) for NE, 39.4% (14.7%) for DUI, and 32.4% (17.6%) for FI.For mild ID (IQ: 50–70), the rates at age 7 (20) years were11.1% (0) for NE, 16.7% (5.6%) for DUI, and 2.8% (0) for FI.2

In comparison to these population-based rates, inconti-nence was more prevalent in this study, which could be dueto selection effects. Motivated parents might be more likely tojoin parent self-help groups and support research. On the oth-er hand, the information on incontinence was assessed in amore detailed questionnaire than is possible in a population-based design.2 Alternatively, persons with FXS and PWS couldsimply be more affected by incontinence than other types ofID, that is, incontinence could be syndrome-specific.

The rate of all types of incontinence (NE, DUI, and FI) wasalso higher than in the previous Dutch study on PWS.10 How-ever, the pattern remains the same: persons with PWS are pri-marily affected by NE and reported to be deep sleepers in 50%of cases. In contrast, persons with FXS have similar rates of allthree types of incontinence (NE, DUI, and FI) which, again,could be due the high rate of externalizing behavioral prob-lems and lower compliance.

The main asset of this study is that two groups with diag-nosed syndromes of ID were compared. Other studies haveincluded heterogeneous groups of children with both ID and

physical handicap.22,23 Major neurological disorders such astetraparesis—and not just the ID—will have a major influenceon incontinence in these patients. Comparing discrete disor-ders of ID is also required, as IQ-matched control groups with‘‘idiopathic ID’’ (i.e., without discernable causes) are increas-ingly difficult to recruit. With the improvement of moleculargenetic techniques, in only 32% of mild (IQ: 50–70) and 4% ofsevere (IQ < 50) ID no genetic or neurobiological causes couldbe identified. With newer micro-arrays, even more personswith ID can be diagnosed, which means that the remainingcases of ‘‘idiopathic’’ ID will diminish further in future.5

A main limitation of the study is that it is based on parentand caregiver appraisal and not on direct clinical assessment.For example, low fluid intake, which has been reported previ-ously as a problem in ID and physical handicap, might havebeen overlooked by parents.23 Also, the rate of LUTS and con-stipation is lower than previously described.22,23 Dysfunction-al voiding with straining and interrupted uroflow-curvesoccurred in 60.7% of patients, who, in contrast to this study,also had major physical handicaps.22 Without a professionalassessment and urodynamic evaluation subtypes of DUI can-not be distinguished.Another limitation of this questionnaire-based study is that

IQ was not measured uniformly by standardized intelligencetests. Therefore, the exact IQ is not known. As the rate of in-continence increases with low IQ, intelligence needs to be con-sidered as a co-variate in future studies. Moreover, the type ofstool could have been specified with the Bristol Stool FormScale.24 As parents and caregivers were asked to answer 170questions already, unfortunately, no further items could beadded to the questionnaire. The Bristol Stool Scale would be a

TABLE V. Symptoms in the Subgroup of Persons With PWS and FXS With any FI (Total FI; n ¼ 72, age � 4 years)


72 (100) 24 (100) 48 (100)

Been stool continent before 37 (50.7) 15 (60.0) 22 (45.8) n.s.

Continent at age (n ¼ 27; missing values ¼ 10)

0–3 years 9 (24.3) 4 (26.7) 5 (22.7) n.s.a

4–5 years 9 (24.3) 4 (26.7) 5 (22.7)

6–8 years 4 (10.8) 1 (6.7) 3 (13.6)

9–10 years 2 (5.4) 1 (6.7) 1 (4.5)

11–15 years 2 (5.4) 1 (6.7) 1 (4.5)

16–18 years 1 (2.7) 1 (6.7) —

Soils during day 56 (76.7) 17 (68.0) 39 (81.3) n.s.a

Wears diaper 8 (11.0) 2 (8.0) 6 (12.5)

Number of incontinent days/week (n ¼ 58; missing values ¼ 6)

Every day 13 (20.3) 1 (5.3) 12 (26.7) —, 0.004a

3–4�/week 4 (6.4) 2 (10.5) 2 (4.4)

1–2�/week 10 (15.6) — 10 (22.2)

1–2�/month 10 (15.6) 2 (10.5) 8 (17.8)

Less than 1�/month 21 (32.8) 11 (57.9) 10 (22.2)

Number of incontinence episodes/day (n ¼ 52; missing values ¼ 12)

1–2� 47 (73.4) 13 (68.4) 34 (75.6) n.s.

3–4� 4 (6.3) — 4 (8.9)

5–6� 1 (1.6) 1 (5.3) —

Soils at night 16 (21.9) 10 (40.0) 6 (12.5) 7.50 (1), 0.024

Wears diaper 9 (12.3) 3 (12.0) 6 (12.5)

Number of incontinent nights/week (n ¼ 20; missing values ¼ 5)

Every night 5 (19.2) 3 (23.1) 2 (15.4) n.s.a

3–4�/week 4 (15.4) 3 (23.1) 1 (7.7)

1–2�/week 4 (15.4) 1 (7.7) 3 (23.1)

1–2�/month 2 (7.7) 1 (7.7) 1 (7.7)

Less than 1�/month 5 (19.2) 2 (15.4) 3 (23.1)





very useful instrument in future studies. Also, two of the mostimportant genetic neurodevelopmental disorders were com-pared, that is, this was not a case–control study. For futurestudies, a control group would be helpful to compare preva-lence rates of NE, DUI, and FI.

Finally, despite the large sample size, possible heterogeneityof the study groups was not analyzed. Even larger studieswould allow a more detailed subgrouping.

CONCLUSIONS

In conclusion, incontinence is a major problem in personswith ID, not just in childhood but well into adulthood. Patternsof incontinence differ according to types of syndrome, IQ levelsand comorbid behavioral disorder. Incontinence is a distressingproblem for patients, parents, and caregivers. Still, many per-sons are not receiving adequate urological assessment andtreatment—despite the fact that established forms of therapyare also effective in persons with ID and special treatmentpackages have been developed.25,26

ACKNOWLEDGMENTS

We would like to thank the Interessensgemeinschaft Fragiles-X e. V. and Prader–Willi-Syndrome Vereinigung Deutschlande. V. for their excellent support and cooperation in this study.

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Elimination disorders in persons with Prader-Willi and Fragile-X syndromes