Urofacial Syndrome

Clinical characteristics: Urofacial syndrome (UFS; also known as Ochoa syndrome) is characterized by prenatal or childhood onset of urinary bladder voiding dysfunction, abnormal facial movement with expression (resulting from abnormal co-contraction of the corners of the mouth and eyes), and often bowel dysfunction (constipation and/or encopresis). Bladder voiding dysfunction can present before birth as megacystis. In infancy and later childhood, UFS can present with a poor urinary stream and dribbling incontinence; incomplete bladder emptying can lead to urinary infection with progressive kidney failure. Investigations after birth can show abnormal bladder contractility and vesicoureteral reflux of urine into the ureter and renal pelvis. Nocturnal lagophthalmos (incomplete closing of the eyes during sleep) has also been documented.

Diagnosis/testing: The clinical diagnosis of UFS can be established in an individual with urinary tract dysfunction and characteristic facial movement with expression, or the molecular diagnosis can be established in an individual with characteristic features and biallelic pathogenic variants in either HPSE2 or LRIG2 identified by molecular genetic testing.

Management: Treatment of manifestations: Rapid and complete antibiotic therapy for acute urinary tract infections. Anticholinergic and alpha-1 adrenergic blocking medications can respectively lower raised pressure within the bladder and enhance voiding of urine. Drug treatment can be complemented by intermittent catheterization per urethra or through vesicostomy. Management of kidney disease per nephrology; management of severe kidney failure may warrant long-term dialysis and kidney transplantation. Lubricant eye drops during the day and eye ointment at night under the care of an ophthalmologist for nocturnal lagophthalmos; standard management for constipation and encopresis.

Surveillance: Ultrasonography to monitor for evidence of urinary tract dysfunction including incomplete bladder emptying and hydroureteronephrosis. Kidney excretory function should be monitored, initially by measuring plasma creatinine at intervals determined by urinary tract features at presentation and their subsequent progression. Ophthalmology examinations to assess for corneal involvement; assessment for bowel dysfunction annually or at each visit.

Agents/circumstances to avoid: Nephrotoxic substances.

Evaluation of relatives at risk: At-risk sibs: it is appropriate to examine sibs of an affected individual as soon as possible after birth to determine if facial and/or urinary tract manifestations of UFS are present to allow prompt evaluation of the urinary tract and renal function and initiation of necessary treatment. At-risk fetus: although no guidelines for prenatal management of UFS exist, it seems appropriate to perform ultrasound examination of pregnancies at risk (in the second and third trimesters) to determine if urinary tract involvement of UFS is present, as this may influence the timing and/or location of delivery (e.g., in a tertiary medical center that could manage renal/urinary complications immediately after birth).

Genetic counseling: UFS is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a UFS-related pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the UFS-related pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.