CDH1-associated Blepharocheilodontic Syndrome Registry

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-06-17

Study Completion Date

2040-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Registry for Primary Ciliary Dyskinesia

NCT03271840

Primary Ciliary Dyskinesia

COMPLETED

International Primary Ciliary Dyskinesia (PCD) Registry

NCT02419365

Primary Ciliary Dyskinesia (PCD)

RECRUITING

A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes

NCT02439645

Long qt Syndrome Torsade de Pointes

TERMINATED

Pediatric Radio Frequency Coils Generic

NCT01633866

Duchenne Muscular Dystrophy Musculoskeletal Abnormalities

ACTIVE_NOT_RECRUITING

Microbiological Examination of Children Operated for Congenital Lacrimal Stenosis

NCT00312689

Congenital Lacrimal Stenosis

UNKNOWN

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Blepharocheilodontic Syndrome

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Individuals identified as having a CDH1 variant and features of blepharocheilodontic syndrome

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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)