Blepharocheilodontic SyndromeNCT07133464
CDH1-associated Blepharocheilodontic Syndrome Registry
An observational study of Blepharocheilodontic Syndrome, run by Ohio State University at 1 site in United States.
Trial summary
The aim of the CDH1-associated Blepharocheilodontic Syndrome (BCDS) registry is to better characterize the clinical features of this condition and exploring whether CDH1 variants linked to BCDS may also increase cancer risk. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Blepharocheilodontic Syndrome
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jun 2025to Jan 2040
- How long will I take part?
- 20 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study participation is not limited by location. There are two ways eligible patients can be referred: * Provider referral: The registry can be discussed with the potential study participant, and if they're interested, verbal permission can be obtained for our study team to reach out. With their consent, the study participant's name and preferred contact information can be sent to bcdsregistry@osumc.edu. * Self-referral: Potential study participants can express interest in study participation by visiting the registry website (https://redcap.link/BCDSregistry).
Who may be able to join
- A documented pathogenic, likely pathogenic or a variant of uncertain significance in the CDH1 gene
- Clinical features that are diagnostic for, or suggestive of, BCDS (cleft lip and/or palate, eyelid anomalies, dental abnormalities, webbed toes, imperforate anus, etc)
Who cannot join
- Non-English-speaking individuals
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The Ohio State University
Columbus, Ohio, 43221
Maegan E Roberts, MS, 614-814-1047, maegan.roberts@osumc.edu
Peter P Stanich, MD, 614-814-1047, peter.stanich@osumc.edu
About this study
The aim of the CDH1-associated Blepharocheilodontic Syndrome (BCDS) registry is to better characterize the clinical features of this condition and exploring whether CDH1 variants linked to BCDS may also increase cancer risk.
Read the detailed description
Blepharocheilodontic Syndrome (BCDS) is a rare genetic disorder characterized by cleft lip and/or palate (CL/P), eyelid malformations, and features suggestive of ectodermal dysplasia. Variants in the CDH1 gene, which encodes the cell adhesion protein E-cadherin, have been implicated in BCDS. Functional studies have demonstrated that CDH1 plays a critical role in lip and palate development during embryogenesis (Ghoumid 2017; Figueiredo 2019).
In the hereditary cancer genetics community, CDH1 is more commonly associated with hereditary diffuse gastric and lobular breast cancer syndrome (DGLBC). CDH1 variants linked to DGLBC are typically truncating mutations, resulting in a null allele. In contrast, CDH1 variants observed in individuals with BCDS are often missense mutations located in the EC1-EC2 linker region (amino acids 254-257) or exon 9 donor splice site variants (e.g., c.1320G>T, c.1320+1G>A, c.1320+1G>T, c.1320+1G>C, c.1320+5G>A) (Ghoumid 2017; Kievit 2018).
Historically, it was believed that individuals with BCDS-associated CDH1 missense variants were not at increased risk for DGLBC-associated cancers. This assumption was based on the absence of reported cancer cases in published BCDS families and epidemiological data from the CDH1 ClinGen Variant Curation Expert Panel (VCEP), which suggested that missense variants may not confer elevated cancer risk (Ghoumid 2017; Kievit 2018; Lee 2018).
However, a 2020 case report by LeBlanc et al. described a family with a known BCDS-associated CDH1 missense variant (c.768T>A, p.N256K), in which a 37-year-old male developed diffuse gastric cancer. This report raised concerns about potential cancer risks in individuals with BCDS-associated CDH1 variants and prompted questions regarding the need for endoscopic screening and other surveillance measures.
Currently, data regarding cancer risk in individuals with CDH1 variants and the BCDS phenotype are limited. The condition is rare, and affected individuals are often identified through exome sequencing due to multiple congenital anomalies. The interpretation of familial cancer risk is further complicated by a high rate of de novo mutations and limited family history.
To address these gaps, this registry aims to establish a centralized, international cohort of individuals with CDH1-associated BCDS. The goal is to better characterize the genotype-phenotype correlations, define the clinical spectrum, and assess the potential cancer risks associated with these variants.
- Conditions
- Blepharocheilodontic Syndrome
- Keywords
- CDH1, Blepharocheilodontic Syndrome, Blepharocheilodontic, BCDS, CDH1-associated Blepharocheilodontic Syndrome, ectodermal dysplasia, cleft lip and palate, eyelid malformations
- Medical subject headings
- Blepharo-cheilo-dontic syndrome, Ectodermal Dysplasia, Cleft Lip
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals identified as having a CDH1 variant and features of blepharocheilodontic syndrome | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comprehensive characterization of the clinical phenotype associated with CDH1-associated blepharocheilodontic syndrome (BCDS)
Reporting of currently known clinical characteristics of CDH1-associated Blepharocheilodontic Syndrome (BCDS), including but not limited to cleft lip and/or palate, eyelid anomalies, dental abnormalities, webbed toes, and imperforate anus. The study will also document additional clinical features that may not have been previously reported in the literature, with the goal of expanding the phenotypic understanding of this rare condition.
Measured: 5 years
Secondary outcomes (1)
Development of evidence-based cancer surveillance recommendations for individuals with CDH1-assocaited blepharocheilodontic syndrome.
Personal and family cancer history will be collected and reviewed annually to evaluate potential cancer risks associated with CDH1 variants in individuals with blepharocheilodontic syndrome (BCDS). For participants who are of appropriate age and undergoing endoscopic surveillance as part of their routine medical care, relevant endoscopic and pathology reports will be obtained and analyzed to assess the presence and prevalence of signet ring cells, a hallmark of diffuse gastric cancer. This comprehensive data collection will support efforts to develop evidence-based cancer surveillance recommendations tailored to individuals with CDH1-associated BCDS.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2025
- Study start17 Jun 2025
- Primary completionJan 2040 (estimated)
- Study completionJan 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Blepharocheilodontic SyndromeStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 20 Years
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maegan Roberts, Ohio State University
- Investigators
- Maegan E Roberts, MS, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07133464
- Sponsor's protocol ID
- STUDY20250005
- Status last verified
- Aug 2025
- First submitted
- 8 Aug 2025
- Last updated
- 21 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data will not be broadly shared. However, external requests for data access may be considered for use in downstream research protocols. All such requests must include an IRB-approved protocol and a formal application for data use. The BCDS Registry Advisory Board, comprising the Principal Investigator and at least one co-investigator, will review applications based on scientific merit and relevance, with input from a statistician as needed. For approved requests, data will be shared via a secure "data push," typically involving export from REDCap to a coded-limited file format. The individual responsible for data transfer will be certified as an honest broker under the OSUWMC Honest Broker Protocol. All studies using registry data will be conducted under separate IRB oversight.
Publications
Lee K, Krempely K, Roberts ME, Anderson MJ, Carneiro F, Chao E, Dixon K, Figueiredo J, Ghosh R, Huntsman D, Kaurah P, Kesserwan C, Landrith T, Li S, Mensenkamp AR, Oliveira C, Pardo C, Pesaran T, Richardson M, Slavin TP, Spurdle AB, Trapp M, Witkowski L, Yi CS, Zhang L, Plon SE, Schrader KA, Karam R. Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants. Hum Mutat. 2018 Nov;39(11):1553-1568. doi: 10.1002/humu.23650.
PubMed 30311375Kievit A, Tessadori F, Douben H, Jordens I, Maurice M, Hoogeboom J, Hennekam R, Nampoothiri S, Kayserili H, Castori M, Whiteford M, Motter C, Melver C, Cunningham M, Hing A, Kokitsu-Nakata NM, Vendramini-Pittoli S, Richieri-Costa A, Baas AF, Breugem CC, Duran K, Massink M, Derksen PWB, van IJcken WFJ, van Unen L, Santos-Simarro F, Lapunzina P, Gil-da Silva Lopes VL, Lustosa-Mendes E, Krall M, Slavotinek A, Martinez-Glez V, Bakkers J, van Gassen KLI, de Klein A, van den Boogaard MH, van Haaften G. Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome. Eur J Hum Genet. 2018 Feb;26(2):210-219. doi: 10.1038/s41431-017-0010-5. Epub 2018 Jan 18.
PubMed 29348693Ghoumid J, Stichelbout M, Jourdain AS, Frenois F, Lejeune-Dumoulin S, Alex-Cordier MP, Lebrun M, Guerreschi P, Duquennoy-Martinot V, Vinchon M, Ferri J, Jung M, Vicaire S, Vanlerberghe C, Escande F, Petit F, Manouvrier-Hanu S. Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1. Genet Med. 2017 Sep;19(9):1013-1021. doi: 10.1038/gim.2017.11. Epub 2017 Mar 16.
PubMed 28301459Figueiredo J, Melo S, Carneiro P, Moreira AM, Fernandes MS, Ribeiro AS, Guilford P, Paredes J, Seruca R. Clinical spectrum and pleiotropic nature of CDH1 germline mutations. J Med Genet. 2019 Apr;56(4):199-208. doi: 10.1136/jmedgenet-2018-105807. Epub 2019 Jan 19.
PubMed 30661051
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CDH1-associated Blepharocheilodontic Syndrome Registry
- ClinicalTrials.gov ID
- NCT07133464
- Acronym / sponsor ID
- STUDY20250005
- Conditions
- Blepharocheilodontic Syndrome
- Keywords
- CDH1, Blepharocheilodontic Syndrome, Blepharocheilodontic, BCDS, CDH1-associated Blepharocheilodontic Syndrome, ectodermal dysplasia, cleft lip and palate, eyelid malformations
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 17 Jun 2025 (actual)
- Primary completion
- Jan 2040 (estimated)
- Study completion
- Jan 2040 (estimated)
- First posted
- 21 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the CDH1-associated Blepharocheilodontic Syndrome (BCDS) registry is to better characterize the clinical features of this condition and exploring whether CDH1 variants linked to BCDS may also increase cancer risk.
Detailed description
Blepharocheilodontic Syndrome (BCDS) is a rare genetic disorder characterized by cleft lip and/or palate (CL/P), eyelid malformations, and features suggestive of ectodermal dysplasia. Variants in the CDH1 gene, which encodes the cell adhesion protein E-cadherin, have been implicated in BCDS. Functional studies have demonstrated that CDH1 plays a critical role in lip and palate development during embryogenesis (Ghoumid 2017; Figueiredo 2019).
In the hereditary cancer genetics community, CDH1 is more commonly associated with hereditary diffuse gastric and lobular breast cancer syndrome (DGLBC). CDH1 variants linked to DGLBC are typically truncating mutations, resulting in a null allele. In contrast, CDH1 variants observed in individuals with BCDS are often missense mutations located in the EC1-EC2 linker region (amino acids 254-257) or exon 9 donor splice site variants (e.g., c.1320G>T, c.1320+1G>A, c.1320+1G>T, c.1320+1G>C, c.1320+5G>A) (Ghoumid 2017; Kievit 2018).
Historically, it was believed that individuals with BCDS-associated CDH1 missense variants were not at increased risk for DGLBC-associated cancers. This assumption was based on the absence of reported cancer cases in published BCDS families and epidemiological data from the CDH1 ClinGen Variant Curation Expert Panel (VCEP), which suggested that missense variants may not confer elevated cancer risk (Ghoumid 2017; Kievit 2018; Lee 2018).
However, a 2020 case report by LeBlanc et al. described a family with a known BCDS-associated CDH1 missense variant (c.768T>A, p.N256K), in which a 37-year-old male developed diffuse gastric cancer. This report raised concerns about potential cancer risks in individuals with BCDS-associated CDH1 variants and prompted questions regarding the need for endoscopic screening and other surveillance measures.
Currently, data regarding cancer risk in individuals with CDH1 variants and the BCDS phenotype are limited. The condition is rare, and affected individuals are often identified through exome sequencing due to multiple congenital anomalies. The interpretation of familial cancer risk is further complicated by a high rate of de novo mutations and limited family history.
To address these gaps, this registry aims to establish a centralized, international cohort of individuals with CDH1-associated BCDS. The goal is to better characterize the genotype-phenotype correlations, define the clinical spectrum, and assess the potential cancer risks associated with these variants.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 20 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals identified as having a CDH1 variant and features of blepharocheilodontic syndrome | – | – |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study participation is not limited by location. There are two ways eligible patients can be referred: * Provider referral: The registry can be discussed with the potential study participant, and if they're interested, verbal permission can be obtained for our study team to reach out. With their consent, the study participant's name and preferred contact information can be sent to bcdsregistry@osumc.edu. * Self-referral: Potential study participants can express interest in study participation by visiting the registry website (https://redcap.link/BCDSregistry).
Key inclusion criteria (2 listed)
- A documented pathogenic, likely pathogenic or a variant of uncertain significance in the CDH1 gene
- Clinical features that are diagnostic for, or suggestive of, BCDS (cleft lip and/or palate, eyelid anomalies, dental abnormalities, webbed toes, imperforate anus, etc)
Key exclusion criteria (1 listed)
- Non-English-speaking individuals
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Comprehensive characterization of the clinical phenotype associated with CDH1-associated blepharocheilodontic syndrome (BCDS)
Time frame: 5 years
Reporting of currently known clinical characteristics of CDH1-associated Blepharocheilodontic Syndrome (BCDS), including but not limited to cleft lip and/or palate, eyelid anomalies, dental abnormalities, webbed toes, and imperforate anus. The study will also document additional clinical features that may not have been previously reported in the literature, with the goal of expanding the phenotypic understanding of this rare condition.
1 secondary outcome
Development of evidence-based cancer surveillance recommendations for individuals with CDH1-assocaited blepharocheilodontic syndrome.
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
- Background: PubMed 30311375Lee K, Krempely K, Roberts ME, Anderson MJ, Carneiro F, Chao E, Dixon K, Figueiredo J, Ghosh R, Huntsman D, Kaurah P, Kesserwan C, Landrith T, Li S, Mensenkamp AR, Oliveira C, Pardo C, Pesaran T, Richardson M, Slavin TP, Spurdle AB, Trapp M, Witkowski L, Yi CS, Zhang L, Plon SE, Schrader KA, Karam R. Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants. Hum Mutat. 2018 Nov;39(11):1553-1568. doi: 10.1002/humu.23650.
- Background: PubMed 29348693Kievit A, Tessadori F, Douben H, Jordens I, Maurice M, Hoogeboom J, Hennekam R, Nampoothiri S, Kayserili H, Castori M, Whiteford M, Motter C, Melver C, Cunningham M, Hing A, Kokitsu-Nakata NM, Vendramini-Pittoli S, Richieri-Costa A, Baas AF, Breugem CC, Duran K, Massink M, Derksen PWB, van IJcken WFJ, van Unen L, Santos-Simarro F, Lapunzina P, Gil-da Silva Lopes VL, Lustosa-Mendes E, Krall M, Slavotinek A, Martinez-Glez V, Bakkers J, van Gassen KLI, de Klein A, van den Boogaard MH, van Haaften G. Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome. Eur J Hum Genet. 2018 Feb;26(2):210-219. doi: 10.1038/s41431-017-0010-5. Epub 2018 Jan 18.
- Background: PubMed 28301459Ghoumid J, Stichelbout M, Jourdain AS, Frenois F, Lejeune-Dumoulin S, Alex-Cordier MP, Lebrun M, Guerreschi P, Duquennoy-Martinot V, Vinchon M, Ferri J, Jung M, Vicaire S, Vanlerberghe C, Escande F, Petit F, Manouvrier-Hanu S. Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1. Genet Med. 2017 Sep;19(9):1013-1021. doi: 10.1038/gim.2017.11. Epub 2017 Mar 16.
- Background: PubMed 30661051Figueiredo J, Melo S, Carneiro P, Moreira AM, Fernandes MS, Ribeiro AS, Guilford P, Paredes J, Seruca R. Clinical spectrum and pleiotropic nature of CDH1 germline mutations. J Med Genet. 2019 Apr;56(4):199-208. doi: 10.1136/jmedgenet-2018-105807. Epub 2019 Jan 19.
- CDH1-associated blepharocheilodontic syndrome (BCDS) registry websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data will not be broadly shared. However, external requests for data access may be considered for use in downstream research protocols. All such requests must include an IRB-approved protocol and a formal application for data use. The BCDS Registry Advisory Board, comprising the Principal Investigator and at least one co-investigator, will review applications based on scientific merit and relevance, with input from a statistician as needed. For approved requests, data will be shared via a secure "data push," typically involving export from REDCap to a coded-limited file format. The individual responsible for data transfer will be certified as an honest broker under the OSUWMC Honest Broker Protocol. All studies using registry data will be conducted under separate IRB oversight.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maegan E Roberts, MS principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Blepharocheilodontic Syndrome, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maegan E Roberts, MS (614-814-1047, maegan.roberts@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comprehensive characterization of the clinical phenotype associated with CDH1-associated blepharocheilodontic syndrome (BCDS) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07133464, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025; AzTrials last refreshed its copy on 31 Oct 2026.