Clinical Description
The main features of urofacial syndrome (UFS) are congenital urinary bladder voiding dysfunction and an abnormality of facial movement with expression that can be observed from birth. Bowel dysfunction is common. In rare instances, an individual who has: (a) a molecularly confirmed diagnosis; and/or (b) an affected relative meeting clinical diagnostic criteria manifests only the characteristic facial features or only the urinary bladder voiding dysfunction (not both).
Significant inter- and intrafamilial phenotypic variability has been observed [Ochoa 1992, Aydogdu et al 2010, Stuart et al 2013, Stuart et al 2015].
Urinary tract features are the main reason for presenting to medical attention and the main cause of associated morbidity and mortality.
UFS is not associated with growth or developmental abnormality other than that attributable to chronic renal disease. Intellect is normal.
Urinary tract. Urinary tract features have been present in all but two of more than 150 clinically defined individuals [Aydogdu et al 2010, Stuart et al 2013, Stuart et al 2015].
Antenatal ultrasound examination (if performed) is frequently described as abnormal and is associated with megacystis, hydroureteronephrosis, and renal pelvis dilatation [Skálová et al 2006, Bacchetta & Cochat 2010, Daly et al 2010, Stuart et al 2013].
Severe neonatal and infant presentations with urinary tract complications including urinary bladder rupture and sepsis have been reported [Ochoa 1992, Skálová et al 2006].
More typical presentations of urinary tract features include recurrent urinary sepsis and failure to achieve urinary continence [Ochoa 1992, Ochoa 2004].
In the Ochoa cohort hydroureteronephrosis was found in 29/50 (58%) of affected individuals [Ochoa 1992, Ochoa 2004], a finding consistent with the range of urinary tract abnormalities in other case reports [Chauve et al 2000, Garcia-Minaur et al 2001, Al-Qahtani 2003, Nicanor et al 2005, Skálová et al 2006, Derbent et al 2009, Aydogdu et al 2010, Daly et al 2010, Stamatiou & Karakos 2010, Sutay et al 2010, Al Badr et al 2011, Akl & Al Momany 2012, Mahmood et al 2012, Stuart et al 2013, Stuart et al 2015].
Ochoa [2004] identified vesicoureteric reflux in 32/50 (64%); reflux was bilateral in 18 (36%).
The associated renal parenchymal damage with early impairment of renal function and progression to end-stage renal disease causes substantial morbidity and mortality [Ochoa 2004, Skálová et al 2006, Sutay et al 2010, Mahmood et al 2012]. The proportion of individuals who develop renal impairment is unknown but likely to be significant [Ochoa & Gorlin 1987, Ochoa 1992, Ochoa 2004, Aydogdu et al 2010].
Facial expression. The most prominent facial feature, abnormal co-contraction of the corners of the mouth and eyes, is most obvious during smiling or laughing [Ochoa 2004, Aydogdu et al 2010, Ganesan & Thomas 2011] and can be socially debilitating.
Symmetric partial facial paresis in the distribution of the facial nerve has been noted; however, the proportion of individuals in whom weakness is a significant feature is unknown [Garcia-Minaur et al 2001; Author, personal observation].
Abnormal facial movement with crying has been observed as early as the neonatal period [Ochoa 1992, Skálová et al 2006].
Nocturnal lagophthalmos (incomplete closing of the eyes during sleep) appears to be a common and significant finding that may lead to keratitis, corneal abrasion, infection, vascularization, and in extreme cases, ocular perforation, endophthalmitis, and loss of the eye [Mermerkaya et al 2014].
Typical facial expressions have been present in all but one affected individual (who was diagnosed due to classic features in a relative) [Aydogdu et al 2010].
Rarely, affected individuals may have a facial phenotype with no urinary bladder dysfunction or symptoms [Stuart et al 2013; Author, personal communication].
Gastrointestinal tract. Constipation is reported in about 66% of affected individuals; encopresis is present in 33% [Ochoa 2004].
Fecal retention in the neonatal period has been noted once [Nicanor et al 2005].
Rectal prolapse has also been reported once in association with severe constipation [Al Badr et al 2011].
MRI of the central nervous system (CNS) – performed because the urinary tract features mimic those associated with CNS dysfunction – is typically normal [Nicanor et al 2005, Derbent et al 2009, Aydogdu et al 2010, Al Badr et al 2011, Akl & Al Momany 2012].
UFS most likely results from an abnormality of peripheral rather than central nervous system development [Roberts et al 2014], although affected individuals do not typically show any other features of neurologic dysfunction.
Note: Although early descriptions of UFS reported individuals with central nervous system abnormalities including spina bifida occulta, occipital meningocele, and hydrocephalus due to stenosis of the aqueduct of Sylvius, the subsequent failure to identify these findings indicates that they were most likely chance associations [Elejalde 1979, Teebi & Hassoon 1991].