EARLY
DIAGNOSIS OF THE UROFACIAL SYNDROME IS ESSENTIAL TO PREVENT IRREVERSIBLE
RENAL FAILURE
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FRANCISCO A. NICANOR, ANTHONY COOK, JOAO L PIPPI-SALLE
Division of Urology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
ABSTRACT
Introduction:
The urofacial or Ochoa syndrome is a rare disease characterized by the
presence of functional obstructive uropathy associated with peculiar facial
features when patients attempt to smile or laugh. Unfortunately, many
of these patients remain without proper diagnosis or adequate treatment
due to lack of recognition of the disease. This can ultimately result
in upper tract deterioration and eventual renal failure. We present our
experience with this rare syndrome.
Materials and Methods: We identified 3 patients
who presented initially with acute renal failure, urinary tract infection
(UTI) and severe dysfunctional elimination. All patients were thoroughly
evaluated, including screening for spinal cord anomalies, and were subsequently
diagnosed with urofacial syndrome.
Results: At the outset, the two older patients
(aged 4 and 9 years) presented with the typical facial features when attempting
to smile or laugh. One patient in the newborn period presented with urinary
and fecal retention and septicemia and, to our knowledge, represents the
youngest case of urofacial syndrome reported so far. All patients were
evaluated with ultrasonography, renal scan, voiding cystourethrogram (VCUG)
and urodynamics. Findings included hydronephrosis and a thick-walled,
trabeculated bladder with poor compliance and detrusor hypereflexia respectively
in each patient. All were subsequently treated with clean intermittent
catheterization (CIC), antibiotic prophylaxis and anticholinergic therapy.
One patient required appendicovesicostomy for CIC due to discomfort secondary
to a sensate urethra.
Conclusions: Our series demonstrates that
early recognition of this rare syndrome is necessary to adequately treat
and prevent upper tract deterioration in these unique individuals. Although
the urofacial is difficult to diagnose in infants, cognizance must be
maintained in order to prevent severe subsequent sequalae.
Key
words: bladder neurogenic; spastic neurogenic bladder; renal
failure; syndrome; facies
Int Braz J Urol. 2005; 31: 477-81
INTRODUCTION
In
the early 1960s, Bernardo Ochoa followed a group of children with the
characteristic symptomatology of neurogenic bladder (recurrent urinary
infection, incontinence, constipation, dysuria, frequency, enuresis, bladder
trabeculation and vesicoureteral reflux) with no apparent neurological
or obstructive abnormality. Furthermore, each patient showed a particular
facial expression, i.e., grimacing when they attempted to smile or laugh
(1). This unusual disorder was initially considered a local observation,
but today over 100 patients have been reported in literature.
The urofacial or Ochoa syndrome is a rare
disease that occurs in both sexes and is more frequent when the parents
are closely related. It has been determined to be inherited by an autosomal
recessive pattern (2). A potential gene has been mapped to chromosome
10q23-q24 (1). Patients with Ochoa syndrome present with functional obstructive
uropathy, residual urine, and hydroureteronephrosis. Symptoms are variable
and may consist of urinary tract infection (UTI), urgency, frequency,
incontinence, polyuria, and polydipsia. Many present with elimination
dysfunction (60% constipation and 33% encopresis) (3), and have a characteristic
pathognomonic inversion of the facial expression when they attempt to
smile or laugh. Interestingly, patients demonstrate emotionally congruent
facial expressions when sad or crying.
The laughing and crying centers are located
in upper pons of the midbrain close to the micturition center and it has
been speculated that this is the possible pathophysiological explanation
for this dysfunctional facial characteristic (4).
MATERIALS AND METHODS
We present our experience with three patients with urofacial syndrome. All of them presented initially with acute renal failure, UTI and severe dysfunctional elimination. Follow-up ranged from 2-9 years (average 5 years). All patients underwent voiding cystourethrogram (VCUG), abdominal ultrasound, urodynamic studies and dimercaptosuccinic acid (DMSA) scintigraphy. Spinal magnetic resonance imaging (MRI) was performed in 2 cases.
RESULTS
Case
1: A 4-day-old Caucasian female presented acute urinary and fecal retention.
Her symptoms initially spontaneously resolved, however at 48 days of age,
she returned to hospital with urinary retention and septicemia. Peritoneal
dialysis was started for acute renal failure. Ultrasound showed bilateral
hydroureteronephrosis. Voiding cystourethrogram (VCUG) showed bladder
trabeculation, grade V bilateral reflux and urinary retention. Clean intermittent
catheterization (CIC) was initiated, but upon familial noncompliance a
vesicostomy was performed. Urodynamics showed a poorly compliant, hyperactive
bladder, high voiding pressures and detrusor-sphincter dyssynergia. Treatment
with anticholinergic (propantheline bromide 3 mg/kg/day) resulted in improved
bladder capacity and resolution of reflux. Vesicostomy was closed and
CIC started at 3 years of age. A trial was attempted with an alpha-blocker
(doxazosin) at a dose of 2 mg/day for 6 months without any improvement
whatsoever. Nuclear medicine with dimercaptosuccinic acid (DMSA) showed
normal kidneys bilaterally. She is presently 9 years old, continues on
CIC every 4 hours and remains infection free. Familial pedigree demonstrates
no history of Ochoa syndrome. Figure-1 demonstrates the typical facial
grimaces associated with the syndrome.
Case 2: A 4-year-old Caucasian male, a product
of conception between two first cousins, was initially referred to the
nephrology clinic for evaluation of hydronephrosis, polyuria and polydipsia.
At that time, 14 hour fasting revealed normal urea, creatinine and serum
sodium, effectively ruling-out diabetes insipidus. He was concomitantly
evaluated by pediatric ophthalmology for non-specific visual disturbances
and subsequently underwent a cranial MRI, which was negative for underlying
neuro-pathology. He then went to a local emergency department following
an episode of gross painless hematuria. Evaluation at that time included
an abdominopelvic CT scan that revealed moderate right hydronephrosis.
His gross hematuria spontaneously resolved and he was discharged with
the diagnosis of acute viral cystitis. Thereafter, he was referred for
urologic evaluation and was found to have a long history of irritative
and obstructive voiding symptoms. At this time he had elevated creatinine
and urea. Physical examination, including the elucidation of a smile,
demonstrated the typical urofacial grimacing (Figure-2). The parents revealed
that two aunts had similar smile findings but no urinary retention at
any time. Evaluation, including renal ultrasonography and VCUG, demonstrated
moderate bilateral hydroureteronephrosis and a thick-walled, trabeculated
bladder with no evidence of vesico-ureteral reflux (VUR) or posterior
urethral valve (PUV) respectively (Figure-3). An MRI of the spine was
normal. Urodynamic evaluation demonstrated a poorly compliant, hyperactive
bladder with elevated filling pressures. Bilateral renal scarring was
noted upon DMSA renal scan (Figure-4). He was initially treated with anticholinergic
therapy and CIC, but refused catheterizations from the outset due to a
sensate urethra, and an appendicovesicostomy was performed to ease catheterization.
Follow-up over the past 2 years has demonstrated normalization of serum
creatinine and excellent compliance with respect to CIC every 2 hours
plus ongoing high doses of anticholinergic therapy, which resulted in
significant improvement of the hydroureteronephrosis.
Case 3: A 9-year-old Caucasian female was
referred to the urologic clinic for evaluation of daytime and nocturnal
urinary incontinence, urgency and recurrent urinary tract infection. Physical
examination revealed the classical finding of Urofacial Syndrome, having
the typical smile expression (Figure-5). VCUG demonstrated bladder trabeculation
and bilateral grade III VUR. Renal scarring was noted bilaterally upon
DMSA renal scan. Urodynamics showed a poorly compliant bladder and detrusor
hyperactivity. MRI demonstrated a normal spine and conus medularis. The
patient was started on progressive doses of oxybutinin (up to 7.5 mg tid)
and CIC, which resulted in markedly improved urinary symptoms. Finally,
her family history was also negative for Ochoa syndrome.
COMMENTS
Although
rare, it is important (and extremely simple) to exclude the urofacial
syndrome in patients who present with dysfunctional voiding or dysfunctional
elimination. Early diagnosis and treatment may prevent irreversible damage
to the urinary tract system.
Previously, genetic studies have been carried
out in patients with Ochoa syndrome. The observations of normal parents
with several affected siblings and parental consanguinity at that time
made it clear that inheritance was autosomally recessive, as in our second
case (2,5). It is possible that patients with non-neurogenic bladder or
Hynman syndrome, subclinical neurological bladder, occult neuropathic
bladder, dysfunctional voiding, or dysfunctional elimination may be affected
by the same congenital neurologic disorder at the level of the pontine
micturition center. However, those with Ochoa syndrome also appear to
have concomitant subclinical lesions in the laughing and crying center
(1). As spinal lesion may be a potential underlying disorder, an MRI should
be performed to rule out other possible etiologies, such as cord tethering,
before reaching a final diagnosis.
The presence of renal scarring should be
noted and monitored by DMSA renal scans. Urodynamics are important not
only to document abnormalities but also for follow-up and disease prognostication.
Initially, detrusor hyperreflexia is associated with sphincter dyssinergia,
however, in advanced cases, myogenic detrusor failure may ultimately result
(6).
The aim of treatment is the restoration
of balanced bladder emptying and the prevention of upper tract deterioration.
Drug therapy is guided by urodynamic findings and includes anticholinergics
and antibiotic prophylaxis if secondary UTI persist despite regular bladder
emptying by CIC. Intermittent catheterization is fundamental and patients
with sensate urethras may require continent urinary diversion, such as
appendicovesicostomy. Polyuric patients should undergo nocturnal bladder
emptying with an indwelling nighttime catheter, as this has been shown
to improve overall lower and upper urinary tract function (7).
CONCLUSION
Although rare, the urofacial syndrome is an important, well-recognized entity, which, if not treated adequately, may lead to significant morbidity and even mortality from progressive renal deterioration. One must maintain cognizance and screen for this disorder in patients with a history of severe dysfunctional voiding by greeting each patient with a smile at the time of initial consultation.
REFERENCES
- Ochoa B: Can a congenital dysfunctional bladder be diagnosed from a smile? The Ochoa syndrome updated. Pediatr Nephrol. 2004; 19: 6-12.
- Ochoa B, Gorlin RJ: Urofacial (Ochoa) syndrome. Am J Med Genet. 1987; 27: 661-7.
- Feng WC, Churchill BM: Dysfunctional elimination syndrome in children without obvious spinal cord diseases. Pediatr Clin North Am. 2001; 48: 1489-504.
- Ochoa B: The urofacial (Ochoa) syndrome revisited. J Urol. 1992; 148: 580-3.
- Elejalde BR: Genetic and diagnostic considerations in three families with abnormalities of facial expression and congenital urinary obstruction: “The Ochoa syndrome”. Am J Med Genet. 1979; 3: 97-108.
- Garcia-Minaur S, Oliver F, Yanez JM, Soriano JR, Quinn F, Reardon W: Three new European cases of urofacial (Ochoa) syndrome. Clin Dysmorphol. 2001; 10: 165-70.
- Koff SA, Mutabagani KH, Jayanthi VR: The valve bladder syndrome: pathophysiology and treatment with nocturnal bladder emptying. J Urol. 2002; 167: 291-7.
_____________________
Received:
June 26, 2005
Accepted after revision: July 25, 2005
_______________________
Correspondence address:
Dr. Francisco A. M. Nicanor
805 77 Elm Street M5G 1H4
Toronto, Ontario, Canada
E-mail: nicanoramacedo@hotmail.com