Urofacial syndrome (UFS; Ochoa syndrome) is an autosomal recessive disorder characterized by congenital urinary bladder dysfunction associated with an abnormal facial expression upon smiling, laughing, and crying. Affected individuals have an overactive detrusor muscle that fails to fully ... Urofacial syndrome (UFS; Ochoa syndrome) is an autosomal recessive disorder characterized by congenital urinary bladder dysfunction associated with an abnormal facial expression upon smiling, laughing, and crying. Affected individuals have an overactive detrusor muscle that fails to fully expel urine because of concomitant internal sphincter contraction, and patients may experience lifelong urinary incontinence, recurrent urosepsis, vesicoureteral reflux, and renal failure. In addition, some patients have severe constipation, indicating a generalized elimination defect (summary by Stuart et al., 2013). For a discussion of genetic heterogeneity of UFS, see UFS1 (236730).
Stuart et al. (2013) studied a consanguineous Turkish family in which an 8-year-old girl presented at age 5 years with urosepsis and constipation and was found to have a low-capacity, overactive bladder, as well as bilateral vesicoureteral reflux, ... Stuart et al. (2013) studied a consanguineous Turkish family in which an 8-year-old girl presented at age 5 years with urosepsis and constipation and was found to have a low-capacity, overactive bladder, as well as bilateral vesicoureteral reflux, hydronephrosis, and mild renal impairment. She also displayed the grimace-upon-smiling facies characteristic of urofacial syndrome (UFS). Despite treatment with intermittent catheterization, antimuscarinic drugs, and surgical bladder augmentation, renal failure progressed and peritoneal dialysis was planned. Her asymptomatic 5-year-old brother was recognized to have the facial features of UFS, but his urinary tract was normal by ultrasound and uroflowmetry. In an unrelated consanguineous Turkish family, 2 sisters were affected: a 9-year-old girl with constipation and the facial features of UFS, who presented at 4 years of age with urosepsis and enuresis with a low-capacity, overactive bladder and bilateral vesicoureteral reflux, and a younger sister who presented at 2 years of age with similar features. The older sister underwent a left nephrectomy at 6 years of age for Wilms tumor (see 194070). Stuart et al. (2013) also studied a 5-year-old Spanish girl who was noted to have an abnormal smile at 6 months of age, when investigations revealed an overactive, trabeculated bladder and left vesicoureteral reflux; her course was complicated by urosepsis and constipation.
In affected sibs from a consanguineous Turkish families with urofacial syndrome mapping to chromosome 1p13.2, Stuart et al. (2013) performed exome sequencing and identified homozygosity for a 1-bp deletion in the LRIG2 gene (608869.0001); the mutation segregated with ... In affected sibs from a consanguineous Turkish families with urofacial syndrome mapping to chromosome 1p13.2, Stuart et al. (2013) performed exome sequencing and identified homozygosity for a 1-bp deletion in the LRIG2 gene (608869.0001); the mutation segregated with disease in the family and was not found in variome databases, 116 local exomes, or 94 Turkish controls. In a second consanguineous Turkish family with UFS mapping to 1p13.2, 2 affected sisters were homozygous for a nonsense mutation in LRIG2 (R709X; 608869.0002). A girl with UFS from a nonconsanguinous Spanish family was found by exome and Sanger sequencing to be compound heterozygous for a deletion and an insertion mutation in LRIG2 (608869.0003-608869.0004). Analysis of the LRIG2 gene in 23 patients with 'nonneurogenic neurogenic bladder' (Hinman syndrome) revealed 1 man with bladder dysfunction but without the facial features of UFS who was compound heterozygous for 2 missense mutations in the LRIG2 gene; Stuart et al. (2013) stated that screening of LRIG2 in more individuals with nonsyndromic voiding dysfunction would be required to establish the contribution of LRIG2 to this broader phenotype. The authors also noted that despite somewhat variable lower urinary tract phenotypes, there were no consistent clinical differences between the UFS patients with LRIG2 mutations and those previously reported to have HPSE2 (613469) mutations.