Craniofrontonasal SyndromeNCT00339846
Genetic Analysis of Craniofrontonasal Syndrome
An observational study of Craniofrontonasal Syndrome and CFNS, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
This study will determine whether all patients with craniofrontonasal syndrome (CFNS) have a mutation of a gene called ephrin-B1 (EFNB1). CFNS is one of a group of conditions called craniosynostosis syndromes that result from closure of one or more of the fibrous joints between the bones of the skull before brain… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Craniofrontonasal Syndrome, CFNS
- How many people
- 152 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2005to 17 Sep 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Who may be able to join
- CFNS patients and their families who were previously referred to us; the majority have DNA samples and clinical data already archived in our collection.
Who cannot join
- Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
- We generally reviewed a brief clinical description from the referring physician about a potential research subject to determine that the subject was appropriate to enter into the study. We reserved the right to exclude cases that were clearly not related to our direct research interests.
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens Hospital, Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
This study will determine whether all patients with craniofrontonasal syndrome (CFNS) have a mutation of a gene called ephrin-B1 (EFNB1). CFNS is one of a group of conditions called craniosynostosis syndromes that result from closure of one or more of the fibrous joints between the bones of the skull before brain growth is complete. Because of the premature closure, the brain is not able to grow in its natural shape; instead, there is growth in areas of the skull where the joints have not yet closed. In CFNS, it results in malformation of the skull and face. It is known that the EFNB1 mutation can cause CFNS, and this study will see if the gene change is present in all patients with the disorder.
This study includes patients and family members affected with CFNS. Participants have 1 to 2 teaspoons of blood drawn for genetic studies. A second blood sample may be requested for further research. Some blood may be used to establish a cell line for later studies. This involves growing the white blood cells from the blood sample. The cells can be kept in the laboratory to make more DNA or can be frozen for later use in studies of craniosynostosis. Patients may also have their medical records reviewed to relate gene changes to clinical features in CFNS.
Read the detailed description
The scientific objective of this study is to determine if all patients with Craniofrontonasal Syndrome (CFNS) contain mutations in the ephrin-B1 (EFNB1) gene in Xq12. We will use mutational analysis of EFNB1 as our principal tool to study the genetics of CFNS. Previously, we had mapped the CFNS locus to a 13 cM region in Xp22 using linkage analysis of 12 unrelated CFNS families with 2 or more affected family members in 2-4 generations. More recently there have been two reports that 23 independent CFNS patients all have mutations in the EFNB1 located at Xq12. Hence, either CFNS displays genetic heterogeneity with at least two genes (one in Xp22 and EFNB1) or our previous linkage analysis was inaccurate and all CFNS patients have EFNB1 mutations.
We have previously collected a large number of coded blood samples from patients with DFNS. We propose to sequence the EFNB1 in all 12 of our previously published CFNS families as well as 6 additional families, 22 sporadic CFNS patients, and two CFNS patients with chromosomal anomalies.
We will be sending letters to all physicians who have referred CFNS patients to us in the past for molecular studies. This letter will outline the recent developments identifying EFNB1 as the CFNS gene. We would like to utilize the referring physicians as liaisons between our lab and CFNS patients. Through the referring physicians, we will invite the patients and their families to join a new study if they are interested in obtaining their genetic testing results. All of our results will be confirmed by a CLIA-certified lab prior to being given to patients or referring physicians.
- Conditions
- Craniofrontonasal Syndrome, CFNS
- Keywords
- Craniosynostosis, Craniofrontonasal Syndrome, CFNS
- Medical subject headings
- Craniofrontonasal dysplasia, Craniosynostoses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start5 Jan 2005
- Study completion17 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Craniofrontonasal SyndromeStudies of the same condition, open and under way.
- 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
- Enrolment
- 152 participants
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00339846
- Sponsor's protocol ID
- 999905029
- Other IDs
- 05-HG-N029
- Status last verified
- 17 Sep 2008
- First submitted
- 19 Jun 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Compagni A, Logan M, Klein R, Adams RH. Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell. 2003 Aug;5(2):217-30. doi: 10.1016/s1534-5807(03)00198-9.
PubMed 12919674Davy A, Aubin J, Soriano P. Ephrin-B1 forward and reverse signaling are required during mouse development. Genes Dev. 2004 Mar 1;18(5):572-83. doi: 10.1101/gad.1171704.
PubMed 15037550Feldman GJ, Ward DE, Lajeunie-Renier E, Saavedra D, Robin NH, Proud V, Robb LJ, Der Kaloustian V, Carey JC, Cohen MM Jr, Cormier V, Munnich A, Zackai EH, Wilkie AO, Price RA, Muenke M. A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22. Hum Mol Genet. 1997 Oct;6(11):1937-41. doi: 10.1093/hmg/6.11.1937.
PubMed 9302274
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Analysis of Craniofrontonasal Syndrome
- ClinicalTrials.gov ID
- NCT00339846
- Acronym / sponsor ID
- 999905029
- Conditions
- Craniofrontonasal Syndrome, CFNS
- Keywords
- Craniosynostosis, Craniofrontonasal Syndrome, CFNS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 152 participants
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 5 Jan 2005
- Study completion
- 17 Sep 2008
- First posted
- 21 Jun 2006 (estimated)
- 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.
This study will determine whether all patients with craniofrontonasal syndrome (CFNS) have a mutation of a gene called ephrin-B1 (EFNB1). CFNS is one of a group of conditions called craniosynostosis syndromes that result from closure of one or more of the fibrous joints between the bones of the skull before brain growth is complete. Because of the premature closure, the brain is not able to grow in its natural shape; instead, there is growth in areas of the skull where the joints have not yet closed. In CFNS, it results in malformation of the skull and face. It is known that the EFNB1 mutation can cause CFNS, and this study will see if the gene change is present in all patients with the disorder.
This study includes patients and family members affected with CFNS. Participants have 1 to 2 teaspoons of blood drawn for genetic studies. A second blood sample may be requested for further research. Some blood may be used to establish a cell line for later studies. This involves growing the white blood cells from the blood sample. The cells can be kept in the laboratory to make more DNA or can be frozen for later use in studies of craniosynostosis. Patients may also have their medical records reviewed to relate gene changes to clinical features in CFNS.
Detailed description
The scientific objective of this study is to determine if all patients with Craniofrontonasal Syndrome (CFNS) contain mutations in the ephrin-B1 (EFNB1) gene in Xq12. We will use mutational analysis of EFNB1 as our principal tool to study the genetics of CFNS. Previously, we had mapped the CFNS locus to a 13 cM region in Xp22 using linkage analysis of 12 unrelated CFNS families with 2 or more affected family members in 2-4 generations. More recently there have been two reports that 23 independent CFNS patients all have mutations in the EFNB1 located at Xq12. Hence, either CFNS displays genetic heterogeneity with at least two genes (one in Xp22 and EFNB1) or our previous linkage analysis was inaccurate and all CFNS patients have EFNB1 mutations.
We have previously collected a large number of coded blood samples from patients with DFNS. We propose to sequence the EFNB1 in all 12 of our previously published CFNS families as well as 6 additional families, 22 sporadic CFNS patients, and two CFNS patients with chromosomal anomalies.
We will be sending letters to all physicians who have referred CFNS patients to us in the past for molecular studies. This letter will outline the recent developments identifying EFNB1 as the CFNS gene. We would like to utilize the referring physicians as liaisons between our lab and CFNS patients. Through the referring physicians, we will invite the patients and their families to join a new study if they are interested in obtaining their genetic testing results. All of our results will be confirmed by a CLIA-certified lab prior to being given to patients or referring physicians.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- CFNS patients and their families who were previously referred to us; the majority have DNA samples and clinical data already archived in our collection.
Key exclusion criteria (2 listed)
- Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
- We generally reviewed a brief clinical description from the referring physician about a potential research subject to determine that the subject was appropriate to enter into the study. We reserved the right to exclude cases that were clearly not related to our direct research interests.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 12919674Compagni A, Logan M, Klein R, Adams RH. Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell. 2003 Aug;5(2):217-30. doi: 10.1016/s1534-5807(03)00198-9.
- Background: PubMed 15037550Davy A, Aubin J, Soriano P. Ephrin-B1 forward and reverse signaling are required during mouse development. Genes Dev. 2004 Mar 1;18(5):572-83. doi: 10.1101/gad.1171704.
- Background: PubMed 9302274Feldman GJ, Ward DE, Lajeunie-Renier E, Saavedra D, Robin NH, Proud V, Robb LJ, Der Kaloustian V, Carey JC, Cohen MM Jr, Cormier V, Munnich A, Zackai EH, Wilkie AO, Price RA, Muenke M. A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22. Hum Mol Genet. 1997 Oct;6(11):1937-41. doi: 10.1093/hmg/6.11.1937.
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Craniofrontonasal Syndrome and CFNS, run by National Human Genome Research Institute (NHGRI) 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 1 inclusion and 2 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: finished, as of the sponsor's last update on 2 Jul 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00339846, which also lists 3 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 2 Jul 2017.