Entry - #615112 - UROFACIAL SYNDROME 2; UFS2 - OMIM
# 615112

UROFACIAL SYNDROME 2; UFS2


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
1p13.2 Urofacial syndrome 2 615112 AR 3 LRIG2 608869
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Face
- Abnormal facial expression upon smiling, laughing, or crying
ABDOMEN
Gastrointestinal
- Constipation
GENITOURINARY
Kidneys
- Hydronephrosis
- Renal failure
- Urosepsis
Ureters
- Vesicoureteral reflux
Bladder
- Overactive bladder
- Trabeculated bladder
- Low-capacity bladder
- Enuresis
- Urinary tract infection
MOLECULAR BASIS
- Caused by mutation in the leucine-rich repeats- and immunoglobulin-like domains-containing protein 2 gene (LRIG2, 608869.0001)
Urofacial syndrome - PS236730 - 2 Entries
Location Phenotype Inheritance Phenotype
mapping key
Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
1p13.2 Urofacial syndrome 2 AR 3 615112 LRIG2 608869
10q24.2 Urofacial syndrome 1 AR 3 236730 HPSE2 613469

TEXT

A number sign (#) is used with this entry because of evidence that urofacial syndrome-2 (UFS2) is caused by homozygous or compound heterozygous mutation in the LRIG2 gene (608869) on chromosome 1p13.


Description

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).


Clinical Features

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.


Mapping

In a consanguineous Turkish family in which a girl had urofacial syndrome (UFS) and her brother had the facial features without urinary tract symptoms, Stuart et al. (2013) performed autozygosity mapping and identified a 52-Mb region of homozygosity on chromosome 1p13.2. In an unrelated Turkish family in which 2 sisters had UFS, autozygosity mapping revealed an 8.5-Mb segment on 1p13.2 overlapping that of the first Turkish family.


Inheritance

The transmission pattern of UFS2 in the families reported by Stuart et al. (2013) was consistent with autosomal recessive inheritance.


Molecular Genetics

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.


REFERENCES

  1. Stuart, H. M., Roberts, N. A., Burgu, B., Daly, S. B., Urquhart, J. E., Bhaskar, S., Dickerson, J. E., Mermerkaya, M., Silay, M. S., Lewis, M. A., Olondriz, M. B. O., Gener, B., and 18 others. LRIG2 mutations cause urofacial syndrome. Am. J. Hum. Genet. 92: 259-264, 2013. [PubMed: 23313374, images, related citations] [Full Text]


Creation Date:
Marla J. F. O'Neill : 3/7/2013
carol : 11/04/2022
alopez : 03/12/2013
alopez : 3/7/2013

# 615112

UROFACIAL SYNDROME 2; UFS2


ORPHA: 2704;   DO: 0050816;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
1p13.2 Urofacial syndrome 2 615112 Autosomal recessive 3 LRIG2 608869

TEXT

A number sign (#) is used with this entry because of evidence that urofacial syndrome-2 (UFS2) is caused by homozygous or compound heterozygous mutation in the LRIG2 gene (608869) on chromosome 1p13.


Description

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).


Clinical Features

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.


Mapping

In a consanguineous Turkish family in which a girl had urofacial syndrome (UFS) and her brother had the facial features without urinary tract symptoms, Stuart et al. (2013) performed autozygosity mapping and identified a 52-Mb region of homozygosity on chromosome 1p13.2. In an unrelated Turkish family in which 2 sisters had UFS, autozygosity mapping revealed an 8.5-Mb segment on 1p13.2 overlapping that of the first Turkish family.


Inheritance

The transmission pattern of UFS2 in the families reported by Stuart et al. (2013) was consistent with autosomal recessive inheritance.


Molecular Genetics

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.


REFERENCES

  1. Stuart, H. M., Roberts, N. A., Burgu, B., Daly, S. B., Urquhart, J. E., Bhaskar, S., Dickerson, J. E., Mermerkaya, M., Silay, M. S., Lewis, M. A., Olondriz, M. B. O., Gener, B., and 18 others. LRIG2 mutations cause urofacial syndrome. Am. J. Hum. Genet. 92: 259-264, 2013. [PubMed: 23313374] [Full Text: https://doi.org/10.1016/j.ajhg.2012.12.002]


Creation Date:
Marla J. F. O'Neill : 3/7/2013

Edit History:
carol : 11/04/2022
alopez : 03/12/2013
alopez : 3/7/2013