Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
|First Received Date ICMJE||April 1, 2005|
|Last Updated Date||February 19, 2014|
|Start Date ICMJE||March 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00106977 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)|
|Official Title ICMJE||Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)|
This study will explore the range and type of medical and developmental problems in patients with Muenke syndrome, a condition that results when one or more of the suture between the bones of the skull close before birth. Because of the premature closure, the skull is not able to grow in its natural shape; instead, it compensates with growth in areas of the skull where the sutures have not yet closed. This can result in an abnormally shaped head, wide-set eyes, and flattened cheekbones. Patients may also have an enlarged head, abnormalities of the hands or feet, and hearing loss.
The fibroblast growth factor receptor 3 (FGFR3) gene, which is involved in the development and maintenance of bone tissue, plays a role in Muenke syndrome. In some cases, the FGFR3 mutation is inherited from a parent with Muenke syndrome; in other cases, where there is no family history of the disorder, the mutation occurs anew. A better understanding of this gene may lead researchers to develop better treatments and genetic counseling for people affected by Muenke syndrome.
Patients with Muenke syndrome and their blood relatives may be eligible for this study. Family members with confirmed Muenke syndrome will have genetic counseling, and patients undergo the following tests and procedures:
Craniosynostosis is a common craniofacial abnormality caused by premature fusion of one or several sutures of the skull. The prevalence of craniosynostosis is approximately 1 in 2100 to 3000 births. Originally described by our group, Muenke syndrome (OMIM #602849) is a specific form of craniosynostosis caused by a single nucleotide transversion in fibroblast growth factor receptor 3 (FGFR3), 749 C> G. This mutation encodes the amino acid substitution Pro250Arg. Individuals carrying the Pro250Arg mutation variably manifest coronal suture craniosynostosis, developmental delay, deafness, and carpal and tarsal bone fusion. The purpose of the present study is to increase our understanding of the clinical manifestations of Muenke Syndrome through detailed physical, developmental, neurologic, dental, ophthalmologic, otolaryngologic, audiologic, and radiologic studies. We also plan to examine the spectrum of clinical characteristics of Muenke syndrome to facilitate early diagnosis and clinical management, including genetic counseling. To accomplish this, we plan to enroll approximately 75-100 probands and family members each year, with an enrollment ceiling of 200. Our study has three arms. The clinical arm is the major focus of our study. Patients and their families will be seen at the NIH Clinical Center and Children's National Medical Center. The second arm is DNA banking of clinically unaffected family members. The third arm is a review of medical records for those individuals with Muenke syndrome who are unable or unwilling to participate in the clinical arm. The fourth arm consists of a questionnaire to be completed by patients via phone or email.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||400|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Subjects who have had confirmation of a Pro250Arg mutation in FGFR3 by a CLIA-certified laboratory. Our research team must receive a photocopy of the positive test result in order to enroll a patient in the study. All races and genders are known to be at risk for Muenke syndrome. Nationality or place of origin is not a specific barrier to participation.
Family members (typically parents or siblings) of probands with Muenke syndrome are also eligible to participate.
Patient of interest cases. Geneticists and genetic counselors may refer individuals who are suspected to have Muenke syndrome, but who have not yet been tested for the FGFR3 Pro250Arg mutation. The purpose of enrolling these subjects is to evaluate a wider spectrum of patients for the mutation causing Muenke syndrome. Testing for the Pro250Arg mutation maybe performed at the discretion of our research group. Those individuals who are found to carry the Pro250 Arg mutation may be invited to participate in the clinical study arm and/or medical record review arm of the study. While we do not incomplete penetrance, children who are not eligible for enrollment due to lack of physical findings consistent with Muenke Syndrome will be referred for hearing testing, and further testing if indicated.
Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
Protection of Vulnerable Populations
We reserve the right to exclude individuals for whom the medical risks of travel and evaluation at NIH appear to outweigh the benefits of study participation.
We will not sponsor or encourage FGFR3 mutation testing of asymptomatic children. Family members below the age of 18 years who do not demonstrate physical examination findings consistent with Muenke syndrome will not be eligible for the study.
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00106977|
|Other Study ID Numbers ICMJE||050131, 05-HG-0131|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Human Genome Research Institute (NHGRI)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP