Dysfunctional Voiding as a Presenting Feature of Marfan Syndrome: A Rare Case

ABSTRACT

Dysfunctional voiding is incontinence resulting from voiding-phase dysfunction. It has been associated with various disorders, but there are only 2 known reports of dysfunctional voiding as a presenting feature of Marfan syndrome in the literature. The present case is a 16-year-old boy with dysfunctional voiding who was diagnosed as having failure to void due to sphincter dyssynergy associated with an unsafe bladder, left-sided vesicoureteric reflux, and emerging Marfan syndrome. Diagnosis of Marfan syndrome was based on the number and type of his clinical features. Because of the prohibitive cost of regular botulinum toxin injections to the sphincter in India, the patient's dysfunctional elimination was managed with clean intermittent self-catheterization, anticholinergics, and stool softeners. Follow-up included monitoring the thorax for any signs of increasing aorta size. It is important to predict dysfunctional elimination in children born with any syndrome that has generalized hypermobility of the joints.


Gajanan Bhat, Girish Nelivigi, Maregowda Shivalingiah, Chandrashekhar Ratkal

Department of Urology, Institute of Nephrourology, Karnataka, India

Received November 09, 2010 - Accepted for Publication December 17, 2010


KEYWORDS: Marfan syndrome; Ghent criteria; Dysfunctional voiding.

CORRESPONDENCE: Dr. Gajanan S. Bhat, Resident in Urology, Institute of Nephrourology, Victoria Hospital Campus, Fort Bangalore - 560 002, Karnataka, India ().

CITATION: Urotoday Int J. 2011 Feb;4(1)art14. doi:10.3834/uij.1944-5784.2011.02.14

ABBREVIATIONS AND ACRONYMS: CIC, clean intermittent catheterization; CISC, clean intermittent self-catheterization; DSD, detrusor sphincter dyssynergia.

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INTRODUCTION

Dysfunctional voiding is incontinence resulting from voiding-phase dysfunction [1]. Bladder emptying occurs simultaneously with involuntary striated sphincter contraction in the absence of any element of abdominal straining, either in an attempt to augment bladder contraction or as a response to discomfort during urination. Unequivocal demonstration of this entity requires pressure, flow, and electromyographic evidence [2].

Various disorders have been associated with dysfunctional voiding. In the present case report, we describe a 16-year-old boy who presented to us with dysfunctional voiding and was diagnosed with emerging Marfan syndrome.

CASE REPORT

A 16-year-old boy presented to us with frequency, urgency, urge incontinence, bedwetting, and constipation since childhood. He was poorly built (i.e., his skeletal structure was not proportionate to his chronological age). Clinical examination revealed a palpable bladder, normal perianal sensation, normal rectal sphincter tone, and a normal bulbocavernosus reflex. Biochemical evaluation revealed normal blood biochemistry. Abdominal ultrasound examination showed left-sided gross hydroureteronephrosis and multiple bladder diverticulae. His postvoid residual urine was 300 mL. A micturating cystourethrogram (MCU) showed left-side vesicoureteral reflux (VUR) with multiple bladder diverticulae Figure 1.

A 99mTc-DMSA renogram showed a contracted left kidney with 16% split function and a normally functioning right kidney (84% function). Urodynamic study demonstrated clear detrusor contraction against a striated sphincter contraction with a high-pressure unsafe bladder Figure 2; there was evidence of detrusor sphincter dyssynergia (DSD).

Cystourethroscopy was performed with a short ureteroscope because the entire urethra was extremely narrow. Results revealed a grossly trabeculated bladder with a large volume of residual urine and a large left paraureteral diverticulum. Magnetic resonance imaging (MRI) of the spine showed lumbosacral dural ectasia, which did not explain these urological findings Figure 3.

Our team suspected Marfan syndrome based on the patient's clinical features. Marfan syndrome is a clinical diagnosis, based on revised Ghent criteria of 1996 [3]. Diagnosis is based on involvement of 3 different systems with major criteria and 3 systems with minor criteria. The present patient had major criteria of: (1) pectus carinatum; (2) thumb sign Figure 4a; (3) arm span to height ratio > 1.05; and (4) lumbosacral dural ectasia. He also had minor criteria of: (1) joint hypermobility Figure 4b; (2) high, arched palate; (3) thick lips; (4) long face. In addition, he had xanthomas over the conjunctivae and tongue and interdental papillae. Because there was no involvement of a third organ system in our case, the diagnosis was emerging Marfan syndrome. The nearest differential diagnosis is Ehlers-Danlos syndrome (hypermobility type), which needs skin striae as a diagnostic sign [2].

Further evaluation of the chest was conducted to look for the presence of an aortic aneurysm, which is a known life-threatening complication of Marfan Syndrome; none was noted. Ophthalmological examination was normal. In summary, the patient was diagnosed as having: (1) failure to void due to sphincter dyssynergy associated with an unsafe bladder, (2) left-sided vesicoureteric reflux, and (3) emerging Marfan syndrome.

DISCUSSION

Marfan Syndrome and Dysfunctional Voiding

Marfan syndrome is an autosomal-dominant disorder with a defect in the fibrillin-1 gene on chromosome 15. It can also arise from a new mutation in the fibrillin-1 gene in 15% of the cases. The fibrillin-1 gene directs the cells to make fibrillin-1 protein. Marfan syndrome causes a decrease in the quantity and quality of fibrillin-1 that is deposited in the connective tissue matrix outside of the cell, resulting in its various manifestations [3].

Marfan syndrome as a cause of dysfunctional voiding is extremely rare. The supposed etiology is dysautonomia due to poor supportive tissue in the autonomic nerves supplying the bladder and deficient collagen resulting in the defective bladder architecture itself [3]. Dysautonomia can cause bladder neck dysfunction. However, dysautonomia could not be demonstrated in the present case because we did not perform videourodynamics.

We conducted a search in the PubMed and Medline databases (U.S. National Library of Medicine) for literature published between 1977 and 2009, using the keywords Marfan syndrome, dysfunctional voiding, nonneurogenic dysfunction, neurogenic dysfunction, and bladder dysfunction. The results revealed that there are only 2 cases of Marfan syndrome reported in the literature that had dysfunctional voiding as a feature. In the first case, dysfunctional voiding was an incidental finding in a 40-year-old female with gastrointestinal symptoms [4]. The second case was written by the patient for the Simon Foundation for Continence Web site in 2009 [5]. The patient states that he was diagnosed as having Marfan syndrome when he presented to the urologist with dysfunctional voiding.

Management

The cornerstone of management of dysfunctional voiding associated with Marfan syndrome is early identification and treatment of the complications of the syndrome along with optimal management of the bowel and bladder. It is important to predict dysfunctional elimination syndrome in children born with any syndrome that has generalized hypermobility of the joints, particularly Marfan syndrome [6]. Ideally, management would be started before consequences of bladder dysfunction become apparent; this early management would improve the long-term prognosis. If there is already upper tract deterioration, the prevention of further damage to the upper urinary tract is of paramount importance. From the outset, the goals of management are to minimize secondary damage to the upper urinary tracts and bladder from the neurogenic bladder dysfunction and to achieve safe social continence [7]. Thus, long before continence becomes an issue, management is directed at creating a low-pressure reservoir and ensuring complete and safe bladder emptying.

Clean intermittent catheterization (CIC) or self-catheterization (CISC) in combination with anticholinergics is a standard initial management in neurogenic bladder dysfunction with detrusor hyperactivity [8,9,10]. CIC enables complete bladder emptying and thus avoids bladder residue and consequent risks for infections. In the high-risk bladder with questionable DSD, CIC also allows bladder emptying before the occurrence of otherwise “spontaneous” high-pressure voiding (known to be detrimental for kidney function and drainage). Anticholinergics act by their smooth muscle relaxant effect. Hence, they are used to improve bladder dynamics through suppression of detrusor hypertonicity and hyperreflexia. By doing so, they eliminate high-pressure uninhibited detrusor contractions (and thus urinary leakage). They also prevent high-pressure bladder storage due to detrusor hypertonicity or low-bladder compliance and high-pressure emptying in case of DSD.

In our case, the patient is very young and has already had detrimental effect of high-pressure voiding. The urethra was very narrow and CSIC was difficult. In addition, little is known about bladder behavior in Marfan syndrome because there is hardly any literature. Given such circumstances, we catheterized the patient with a 12-Fr Foley catheter as a temporary measure to decrease the intravesical pressure. Later, CSIC was advised with a 10-Fr urethral catheter. We also prescribed anticholinergics. The bowel dysfunction was treated with stool softeners. The patient is on regular follow-up with abdominal and pelvic sonography every 3 months. The results have not shown any further deterioration in the upper tracts. The follow-up DMSA renogram at the end of the first year did not show any further deterioration in the split and overall renal function.

We considered botulinum injection to the sphincter and the bladder on a regular basis as a treatment for DSD and hyperactive high-pressure detrusor, but the expense of this treatment regimen for patients in our country and chances of poor compliance made us plan an alternative regimen. Hence, the patient was counseled for bladder augmentation and continent catheterizable conduit. This is a safer option for the preservation of upper tracts, even in case of noncompliance by the patient for further treatment and follow-up. In the meantime, his thorax is also being monitored for any signs of increasing aorta size.

CONCLUSION

Dysfunctional voiding as a presenting feature of Marfan syndrome is extremely rare. It is difficult to predict the natural history of the disease with regard to the urogenital system because of little data, although the literature suggests that dysfunctional voiding should be expected for patients born with generalized joint hypermobility. Management of the voiding dysfunction along with regular follow-up to look for thoracic complications is important in such cases.

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