Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
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:
- Medical and family history and physical examination, including body measurements.
- Blood tests to evaluation kidney, liver, heart, and hormonal function, and for genetic studies and other research purposes.
- Dual emission x-ray absorptiometry (DEXA) scan to measure the amount of total body fat. For this test, the subject lies on a table for scanning with low-dose X-rays.
- Computed tomography (in adults) of the abdomen to measure abdominal fat. CT uses a small amount of radiation to obtain images of internal body structures.
- Magnetic resonance imaging (in children) of the abdomen to measure abdominal fat. MRI uses a magnetic field and radio waves to obtain images of internal body structures.
- Oral glucose tolerance tests to measure blood glucose and insulin levels. For this test, the patient drinks a glucose (sugar) solution. Blood samples are drawn through an IV catheter before the test begins and at 1, 2, and 3 hours after drinking the solution.
- Complete eye examination to look for retinal changes and to assess vision, and, if medically needed, an examination of the ear, nose, and throat to check for hearing and breathing abnormalities.
- Tests of learning ability in patients over 5 years of age. For younger patients, a parent is asked about the child's development.
- Ultrasound study of the ovaries and uterus in females and of the testes in males.
- Photographs of the face, hands, feet, body, and genitalia, if the patient agrees.
- Meeting with investigators and a genetic counselor for review of test findings when the studies are completed.
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.
|Official Title:||Bardet-Biedl Syndrome: Phenotype and Metabolic Characteristics|
|Study Start Date:||February 2004|
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.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Leslie G Biesecker, M.D.||National Human Genome Research Institute (NHGRI)|