An observational study in Craniosynostosis and Muenke Syndrome, sponsored by National Human Genome Research Institute (NHGRI). Completed at 2 sites in United States. Open to participants aged 1 Month and older. Per ClinicalTrials.gov, last updated 2020-03-26.
Sponsored by National Human Genome Research Institute (NHGRI) · Observational
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 2,100 to 3,000 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), c.749C>G, resulting in p.Pro250Arg. Individuals carrying the defining 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, radiologic, and genetic/genomic 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 10-20 probands, as well as their family members each year, with an enrollment ceiling of 200 probands. 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. Individuals with Muenke syndrome who are unable or unwilling to come to the NIH, can submit their medical records, including a copy of the molecular testing, for review. The second arm is genetic/genomic studies with the goal of investigating modifying factors that relate to disease severity and expression. The third arm consists of a cognitive function, development and hearing questionnaire to be completed by patients online, via phone or mail.
51 studies on the registry are indexed under Craniosynostoses; 14 are open to participants now.
This study's enrollment of 137 is above the median of 43 across 26 observational studies indexed under Craniosynostoses.
Browse Craniosynostoses studies →National Human Genome Research Institute (NHGRI) is the lead sponsor of 203 studies on the registry; 33 are open to participants now.
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Subjects who have had confirmation of a p.Pro250Arg mutation in FGFR3 by a CLIA-certified laboratory. Family members (typically parents or siblings) of probands with Muenke syndrome are also eligible to participate.@@@@@@
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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 study. Individuals who do not carry the mutation but that have an affected first degree family member will be invited to participate in the
genomic and/or survey arm of the study.
EXCLUSION CRITERIA:
Description and justification of inclusion/exclusion of participants. (age, gender, ethnicity, prisoners, pregnant women, fetuses, decisionally-impaired, healthy volunteers, lab personnel)
It is our intention to remove as many economic, cultural, geographic, racial, and gender barriers as we reasonably can to promote participation of individuals with Muenke syndrome and their families for research purposes. The study will include pediatric and decisionally-impaired individuals, because these characteristics are possible with Muenke syndrome. Pregnant or nursing women may be limited in their participation in some aspects of the study.
As described above, Muenke syndrome has been demonstrated to occur in persons of different ethnic backgrounds. We would make every reasonable effort to encourage the enrollment and participation of a wide spectrum of individuals.
-Pregnant women will not be excluded.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Family members (typically parents or siblings) of probands with Muenke syndrome are alsoeligible to participate.
Subjects who have had confirmation of a p. Pro250Arg mutation in FGFR3 by a CLIA-certified laboratory.
Understanding
The objective of this study is primarily to increase our understanding of the genetics and clinical characteristics of Muenke syndrome.
Time frame: Ongoing
Ran from Mar 2005 to primary completion in Mar 2020, 179 months.
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This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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