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urofacial syndrome 2 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

urofacial syndrome 2

MONDO:0014049

Also known as:LRIG2 Ochoa syndromeOchoa syndrome caused by mutation in LRIG2urofacial syndrome type 2

Overview

Any Ochoa syndrome in which the cause of the disease is a mutation in the LRIG2 gene.

GeneticsAutosomal recessive · LRIG2 (chr 1)

ResearchLimited published research (6 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include very common findings: Vesicoureteral reflux and Urinary urgency; and common findings: Facial grimacing, Enuresis, and Constipation. 11 total HPO annotations.

Organ System	Phenotype Count	Example Features
Kidneys and urinary system	3	Recurrent urinary tract infections, Urinary urgency, Reduced kidney function (renal insufficiency)

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

LRIG2 encodes leucine rich repeats and immunoglobulin like domains 2 (1,065 aa). Highest expression in Ovary (12.7 TPM) and Cervix Ectocervix (11.5 TPM).

Urofacial syndrome 2 is associated with mutations in the LRIG2 gene on chromosome 1.

LRIG2 is classified as a druggable target with score 0.0.

GeneReviews

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No formal diagnostic criteria for urofacial syndrome (UFS) have been published.

Suggestive Findings

UFS should be suspected in individuals with the following clinical findings and family history.

Classic clinical findings

Urinary bladder dysfunction (also termed non-neurogenic neurogenic voiding dysfunction, occult or subclinical neuropathic bladder) with detrusor overactivity and detrusor sphincter dyssynergia . Affected individuals are at risk for urinary incontinence, urosepsis, and progressive kidney failure . Urinary tract features have been present in nearly all reported individuals [, , , , ].

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for urofacial syndrome 2. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for urofacial syndrome (UFS) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with UFS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Urofacial Syndrome: Recommended Evaluations Following Initial Diagnosis

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. Urofacial Syndrome: Recommended Surveillance

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for urofacial syndrome 2.

6 publications have been identified in PubMed for urofacial syndrome 2. Research spans Review / Meta-Analysis (33%), Case Report / Case Series (33%), and Basic Science / Preclinical (33%).

Recent Publications

Del Valle-Peréz M (2025). [PMID: 39150614](https://pubmed.ncbi.nlm.nih.gov/39150614/). *J Appl Genet*. [Case Report / Case Series]
Alkeraithe F (2025). [PMID: 40948727](https://pubmed.ncbi.nlm.nih.gov/40948727/). *Case Rep Urol*. [Case Report / Case Series]
Becker Y (2025). [PMID: 39910799](https://pubmed.ncbi.nlm.nih.gov/39910799/). *Biochem Soc Trans*. [Review / Meta-Analysis]
Vlodavsky I (2024). [PMID: 38747803](https://pubmed.ncbi.nlm.nih.gov/38747803/). *FASEB J*. [Review / Meta-Analysis]
Soboh S (2024). [PMID: 39695102](https://pubmed.ncbi.nlm.nih.gov/39695102/). *Cell Death Dis*. [Basic Science / Preclinical]
Lopes FM (2024). [PMID: 38990208](https://pubmed.ncbi.nlm.nih.gov/38990208/). *Elife*. [Basic Science / Preclinical]

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 5:01 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:615112

GARD

Genetic and Rare Diseases Info Center

GARD:15907

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Clinical Guidance

Urofacial syndrome (UFS) is characterized by urinary bladder voiding dysfunction, abnormal facial expression, and often bowel dysfunction. Significant inter- and intrafamilial phenotypic variability has been observed. To date, more than 150 individuals with UFS have been identified/reported. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Urofacial Syndrome: Frequency of Select Features

Feature	% of Persons w/Feature	Comment
Urinary tract dysfunction	98%	—
Abnormal facial expression	99%	Co-contraction of the corners of the mouth eyes
Nocturnal lagophthalmos	Unknown	Incomplete closing of the eyes during sleep
Constipation	~66%	—
Encopresis	~33%	Urinary tract dysfunction is the main reason for presenting to medical attention and the main cause of associated morbidity and mortality. Urinary tract dysfunction has been present in all but two of more than 150 clinically defined individuals .

Source: GeneReviews — "Urofacial Syndrome"

GeneReviews

Differential Diagnosis

The urinary tract features of urofacial syndrome (UFS) overlap with those seen in association with multiple other conditions . Antenatal or congenital megacystis and/or hydronephrosis • Urethral obstruction due to posterior urethral valves or atresia • Chromosome abnormalities (e.g., megacystis in association with trisomy 21 and 13) • Prune-belly sequence (e.g., caused by biallelic pathogenic variants in CHRM3 or MYOCD) (See .) • Megacystis microcolon intestinal hypoperistalsis syndrome, a heterogeneous condition resulting from smooth muscle dysfunction (See .) Table 3. Monogenic Disorders with Antenatal or Congenital Megacystis and/or Hydronephrosis in the Differential Diagnosis of Urofacial Syndrome

Gene(s)	Disorder	MOI	GI/GU Involvement	Other Features
ACTA2	Multisystem smooth muscle dysfunction syndrome (OMIM 613834) (See also Heritable Thoracic Aortic Disease Overview.)	AD	Hypotonic bladder,1 cryptorchidism, malrotation hypoperistalsis of the gut;2 prune-belly sequence may be associated.3	Thoracic aortic aneurysms aortic dissections, PDA, stenosis dilatation of cerebral vessels, mydriasis, periventricular white matter hyperintensities on MRI, pulmonary hypertension
ACTG2	ACTG2 visceral myopathy (OMIM 619431)	AD3	Mild-to-severe smooth muscle dysfunction of the bladder GI system.; Bladder: neonatal megacystis megaureter (incl prune-belly syndrome) to recurrent urinary tract infections bladder dysfunction; GI: microcolon, CIPO, malrotation, functional intestinal obstruction	—
CHRM3	Prune-belly syndrome (OMIM 100100)	AR	Prune-belly sequence w/distended, areflexic/hyporeflexic bladder; hydroureter, hydronephrosis; cryptorchidism; constipation, posterior urethral valves4	Mydriasis
CHRNA3	Bladder dysfunction, autonomic, w/impaired pupillary reflex secondary CAKUT (OMIM 191800)	AR	Impaired bladder innervation, thick bladder wall, neurogenic vesicoureteral reflux w/hydroureter, hydronephrosis; secondary small, cystic kidneys chronic kidney disease, hypospadias	Impaired pupillary reflex
EBF3	EBF3 neurodevelopmental disorder (OMIM 617330)	AD	~30% of affected persons have renal or lower urinary tract features overlapping w/phenotype in urofacial syndrome.5	Developmental delay, intellectual disability, speech delay, gait or truncal ataxia, hypotonia, behavioral issues, facial dysmorphism
LMOD1	LMOD1-related MMIHS	AR	Classic features of MMIHS (e.g., megacystis, microcolon, intestinal dysmotility)	—
MYH11	MYH11-related MMIHS	AR	Overlapping features of MMIHS prune-belly sequence (1 person); Overlapping features of MMIHS MSMDS (1 person)	PDA in 1 child6
MYL9	MYL9-related MMIHS (OMIM 619365)	AR	MMIHS w/prune-belly sequence	Mydriasis; vascular smooth muscle dysfunction has not been reported.
MYLK	MYLK-related MMIHS (OMIM 249210)	AR	MMIHS	Familial ...

Source: GeneReviews — "Urofacial Syndrome"

System/Concern	Evaluation	Comment
Nocturnal lagophthalmos	Ophthalmologic exam for evidence of nocturnal lagophthalmos	—
Constipation	Assessment of bowel emptying	—
Genetic counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of UFS to facilitate medical personal decision making DMSA = dimercaptosuccinic acid; MOI = mode of inheritance; UFS = urofacial syndrome 1. , , 2.
Urofacial Syndrome: Treatment of Manifestations Manifestation/Concern	Treatment	Considerations/Other Urinary tract dysfunction; Anticholinergic alpha-1 adrenergic blocking medications can respectively lower raised pressure w/in the bladder enhance voiding of urine.
Kidney disease	Mgmt as nephrologist to prevent or slow progression	Mgmt of severe kidney failure may warrant long-term dialysis kidney transplantation.
Abnormal facial expression	Successful treatment w/botulinum toxin has been reported in a single person requires further eval.1	Nocturnal lagophthalmos
Bowel dysfunction	Standard mgmt for constipation encopresis	UFS = urofacial syndrome 1. 2. To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6.
Urofacial Syndrome: Recommended Surveillance System/Concern	Evaluation	Frequency
Urinary tract dysfunction	Ultrasonography to monitor for evidence of urinary tract dysfunction incl incomplete bladder emptying hydroureteronephrosis	At least annually through childhood
Kidney disease	Assessment of kidney excretory function by measurement of plasma creatinine	Per nephrologist determined by urinary tract features at presentation disease progression
Nocturnal lagophthalmos	Ophthalmology exam to assess for evidence of significant corneal involvement	Recommended frequency is undetermined
Bowel dysfunction	Assess for constipation/encopresis by parental report	Annually or at each visit Agents/Circumstances to Avoid Nephrotoxic substances contraindicated in individuals with renal impairment should be avoided if possible. At-risk sibs of a proband.

Kisho

urofacial syndrome 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

urofacial syndrome 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials