Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
|First Submitted Date||February 18, 2004|
|First Posted Date||February 19, 2004|
|Last Update Posted Date||October 6, 2017|
|Start Date||February 17, 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures||Not Provided|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00078091 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Genetics and Clinical Characteristics of Bardet-Biedl Syndrome|
|Official Title||Bardet-Biedl Syndrome: Phenotype and Metabolic Characteristics|
This study will evaluate patients with a rare inherited condition called Bardet-Biedl syndrome . The purpose of the study is to learn more about the genetics and clinical characteristics of this disorder. Patients may have the following problems: polydactyly (extra fingers and toes); retinal dystrophy (changes in the retina that may lead to vision problems, including blindness); obesity and diabetes (overweight and high blood sugar due to failure of body organs to respond to insulin); cognitive dysfunction (difficulties with learning and understanding); hypogenitalism (decreased functioning of the ovaries in women and the testes in men); kidney anomalies (changes in the structure or function of the kidneys); heart disease; and hepatic fibrosis (liver disease).
Patients with Bardet-Biedl syndrome may be eligible for this study. First-degree relatives will also be enrolled for certain tests and procedures. Candidates are screened with a review of their medical records, laboratory tests, and x-rays.
Patients in this study undergo the following tests and procedures:
Relatives of patients have a complete medical and family history and physical examination. Blood is drawn for assessment of kidney, liver, heart, and hormonal function and for genetic study and other research purposes. Relatives over 5 years of age may have tests of learning ability and cognition. For younger patients, a parent is asked about the child's development. Relatives meet with investigators and a genetic counselor for review of test findings when the studies are completed.
|Detailed Description||Although the Bardet-Biedl syndrome (BBS: severe obesity, polydactyly, learning disabilities, retinopathy, renal disease and cardiac malformations) was described more than 80 years ago, it is only over the past few years that extensive data on the natural history and molecular pathogenesis of this complex disorder have been reported. We now know that BBS can be caused by mutations in at least 12, genes and, although it is typically inherited in an autosomal recessive pattern, BBS may occasionally exhibit more complex inheritance. In this study, we are defining the physical (body mass, percent and distribution of body fat) and metabolic (hyperglycemia, hyperinsulinemia, serum levels of lipids and adipokines) characteristics of glucose and fat metabolism in a cohort of adult and pediatric patients with BBS. We are also characterizing the hypogenitalism in BBS, and attempting to determine its relationship, if any, to the incidence of obesity in BBS. In addition, we are studying the retinal dystrophy, the renal dysfunction, and the nature of the reported mental retardation/learning disability that is found in many patients. We plan to correlate the phenotypic manifestations in our subjects with the results of our mutation analysis studies. Our objective is to learn more about the genetic alterations that may underlie the obesity and associated organ dysfunction that characterizes BBS.|
|Study Design||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Estimated Completion Date||February 5, 2016|
|Primary Completion Date||Not Provided|
We are using the previously published clinical diagnostic criteria for BBS(21) to determine study eligibility of probands. As outlined in that report, we are including patients who present with four of the five primary features or three primary features and two secondary features. Parents are also enrolled for genetic studies. We are not enrolling unaffected siblings or recruiting control subjects, instead, results of testing are being compared to previously published data obtained from appropriate non-BBS control subjects.
The initial determination of eligibility is made by review of prior clinical records. Some patients are not characterized in sufficient detail to know if the person meets the clinical criteria, yet we may suspect the diagnosis. In those cases, the subjects are brought to NIH and undergo clinically appropriate testing to make the diagnosis. If that clinical testing does not confirm the diagnosis, the patient or parents are given appropriate clinical counseling and returned to the care of their personal physician. If features later develop that allow the diagnosis to be made, they may re-enroll and undergo further evaluation.
Our study population includes patients of all ages and ethnic groups, and both genders. The inclusion of children is essential to a research study that is correlating genotype with phenotype, and is attempting an early identification of metabolic abnormalities that may be best treated at an early age. Many of the age-dependent manifestations of BBS develop during childhood and the average age of diagnosis is 9.2 years. Pregnant women and children under the age of 5 yr do not undergo invasive research procedures (i.e. phlebotomy) or procedures involving ionizing radiation (i.e. X-rays or DEXA scans) unless that procedure would be performed as part of standard medical care.
Because cognitive dysfunction is known to be a component of BBS, some patients with impaired cognition and understanding may be evaluated under this protocol. If the investigators believe that an adult patient may not be competent to give informed consent to participate, or does not understand the consent document and the procedures of the study, that patient may be excluded from participation. We may request that the patient and accompanying caregiver also be interviewed by an independent ethics panel to confirm that he or she is competent to give consent and to participate if the team feels this would be useful.
Neither healthy volunteers unrelated to an affected patient nor lab personnel will be enrolled.
We will make efforts to obtain consent from all parents/guardians of minor subjects (i.e. we would not allow a single parent to consent a child when both parents have parental rights). If a single parent or guardian has sole custody/legal responsibility for a child (e.g., a divorce with full custody to one parent or one parent is deceased), we will accept consent from one parent.
Both mothers and fathers of children with BBS (who are also typically enrolled in our protocol, as described above) are eligible to participate in the interview portion of the study. We hypothesize that mothers and fathers will, as groups, have slightly different experiences with coping with courtesy stigma, although a couple may have convergent beliefs, coping mechanisms, and experiences. As such, we predict that we will initially conduct interviews with both parents of the same proband (assuming both parents are interested in participating), although we may target either mothers or fathers only following interim analysis of the interview transcripts.
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||040123
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )|
|Study Sponsor||National Human Genome Research Institute (NHGRI)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 5, 2016|