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orofaciodigital syndrome I - Clinical Profile, Genes & Research | Kisho | Kisho

Features include very common findings: Median cleft upper lip, Hypertelorism, Lobulated tongue, and High palate and others; and common findings: Seizure, Polycystic kidney dysplasia, Intellectual disability, and Cleft palate and others. 98 total HPO annotations.

Organ System	Phenotype Count	Example Features
Arms and legs	10	Radial deviation of finger, Short 2nd toe, Hand polydactyly
Head and neck	8	Median cleft upper lip, Cleft palate, Microcephaly
Brain and nerves	7	Seizure, Hydrocephalus, Intellectual disability
Digestive system	5	Hepatic cysts, Pancreatic cysts, Liver scarring (fibrosis) (hepatic fibrosis)
Kidneys and urinary system	4	Polycystic kidney dysplasia, Protein in the urine (proteinuria), Multicystic kidney dysplasia
Skin	3	Alopecia, Tongue nodules, Dry skin
Bones and joints	3	Low bone density (reduced bone mineral density), Bone and joint problems (abnormality of the skeletal system), Hypoplasia of the zygomatic bone
Ears	2	Hearing loss (hearing impairment), Chronic otitis media
Heart and blood vessels	2	Abnormal heart morphology, Hypertension
Growth and development	1	Short stature
Muscles	1	Brain shrinkage (cerebral atrophy)
Lab test results	1	Elevated circulating hepatic transaminase concentration

Age of onset: adulthood.

GeneReviews

Clinical Guidance

The diagnosis of oral-facial-digital syndrome type I (OFD1) is suspected at birth in some infants on the basis of characteristic oral, facial, and digital anomalies; in other instances, the diagnosis is suspected only after polycystic kidney disease is identified in later childhood or adulthood. Almost all affected individuals with OFD1 are female; however, a few affected males have been reported. Most affected males are described as malformed fetuses delivered by a female with OFD1. To date, 234 individuals have been identified with a pathogenic variant in OFD1 . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Oral-Facial-Digital Syndrome Type I: Frequency of Select Features

Feature	% of Persons w/Feature	Comment
Oral manifestations	97%-100%	Dental tongue abnormalities, aberrant oral frenulae, bifid uvula

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 consensus clinical diagnostic criteria for oral-facial-digital syndrome type I (OFD1) have been published.

Suggestive Findings

OFD1 should be suspected in females with typical oral, facial, and digital findings, polycystic kidney disease, and/or milia. The oral, facial, and digital findings are also found in other oral-facial-digital syndromes. OFD1 is characterized by renal cystic disease in approximately 50% of individuals and by the X-linked inheritance pattern in families with more than one affected individual. Almost all individuals with OFD1 are female; however, a few affected males have been reported. Most affected males are described as malformed fetuses delivered by an affected female.

Clinical Features

Oral

Source: GeneReviews — "Oral-Facial-Digital Syndrome Type I"

GeneReviews

Differential Diagnosis

The differential diagnosis of oral-facial-digital syndrome type I (OFD1) includes other oral-facial-digital syndromes and cystic renal diseases. Table 4. Genes of Interest in the Differential Diagnosis of Oral-Facial-Digital Syndrome Type I

Gene(s)	Disorder	MOI	Distinctive Features/ Comment
C2CD3	C2CD3-related OFD(OMIM 615948)/JS-OFD	AR	Severe microcephaly ID. Brain MRI shows vermis hypoplasia MTS.
CEP164	CEP164-related OFD1

Genetic testing for OFD1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for orofaciodigital syndrome I has been reported in the published literature.

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 orofaciodigital syndrome I. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for oral-facial-digital syndrome type I (OFD1) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with OFD1, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Oral-Facial-Digital Syndrome Type I: Recommended Evaluations

System/Concern	Evaluation	Comment
ENT	Exam for oral manifestations that may affect feeding speech	—
Dental	Dental eval	—
Digit anomalies	Assess for digit anomalies.	Neurologic
Behavior	Formal, age-appropriate assessment of development behavior	—
Hearing	Audiology eval if cleft palate is present	—
Genetic counseling	By genetics professionals1

Source: GeneReviews — "Oral-Facial-Digital Syndrome Type I"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Oral-Facial-Digital Syndrome Type I"

Clinical Trials

View trials for orofaciodigital syndrome I

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Prognosis

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

GeneReviews

Surveillance Guidelines

Table 7. Oral-Facial-Digital Syndrome Type I: Recommended Surveillance

System/Concern	Evaluation	Frequency
ENT	Assessment of speech development frequency of ear infections	Annually in children if cleft lip /or cleft palate is present
Dental	Dental eval	Annually or as recommended by dentist in presence of dental abnormalities
Neurologic	Assess for new seizures or changes in seizures.	As recommended by neurologist in those w/brain involvement Renal
Behavior	Monitor developmental progress, educational needs, for behavioral manifestations.	At each visit
Hearing	Audiology eval	Annually

Source: GeneReviews — "Oral-Facial-Digital Syndrome Type I"

Phenotype severity distribution: 9 very common features, 23 common features.

Estimated prevalence: Unknown (Unknown prevalence).

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 orofaciodigital syndrome I.

10 publications have been identified in PubMed for orofaciodigital syndrome I. Research spans Case Report / Case Series (40%), Basic Science / Preclinical (40%), and Diagnostic / Biomarker (10%).

Research Type	Count	% of Total
Patient case studies	4	40%
Laboratory research	4	40%
Testing and diagnosis research	1	10%
Research summaries	1	10%

Recent Publications

van der Westhuizen J (2026). [PMID: 41392822](https://pubmed.ncbi.nlm.nih.gov/41392822/). *American journal of medical genetics. Part A*. [Diagnostic / Biomarker]
Yang M (2025). [PMID: 40059580](https://pubmed.ncbi.nlm.nih.gov/40059580/). *Journal of clinical laboratory analysis*. [Basic Science / Preclinical]
Jones N (2025). [PMID: 41064626](https://pubmed.ncbi.nlm.nih.gov/41064626/). *Case reports in nephrology and dialysis*. [Case Report / Case Series]
Bertiaux E (2025). [PMID: 40667239](https://pubmed.ncbi.nlm.nih.gov/40667239/). *bioRxiv*. [Basic Science / Preclinical]
García-Bohórquez B (2025). [PMID: 40319332](https://pubmed.ncbi.nlm.nih.gov/40319332/). *Human genomics*. [Case Report / Case Series]
Iturrate A (2025). [PMID: 41291844](https://pubmed.ncbi.nlm.nih.gov/41291844/). *Human genomics*. [Review / Meta-Analysis]
Che R (2025). [PMID: 40399278](https://pubmed.ncbi.nlm.nih.gov/40399278/). *Nature communications*. [Basic Science / Preclinical]
Lo Giudice M (2025). [PMID: 40565597](https://pubmed.ncbi.nlm.nih.gov/40565597/). *Genes (Basel)*. [Case Report / Case Series]
Sawada Y (2025). [PMID: 40475304](https://pubmed.ncbi.nlm.nih.gov/40475304/). *Kidney Med*. [Case Report / Case Series]
Hannes L (2024). [PMID: 38158857](https://pubmed.ncbi.nlm.nih.gov/38158857/). *Genetics in medicine : official journal of the American College of Medical Genetics*. [Basic Science / Preclinical]

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orofaciodigital syndrome I

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

orofaciodigital syndrome I

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team