Turner Syndrome: Genotype and Phenotype

NCT00006334 | Completed

• 2 other identifiers: 00021900-CH-0219
• Study Type: observational
• Target: 1,017
• Locations: 1 country
• Sites: 1

Brief Summary

This study examines the clinical and genetic factors related to Turner syndrome, a disorder of the sex chromosomes. Humans usually have 23 pairs of chromosomes-thin strands of DNA-in the nucleus of every cell, which contain genes that determine our hereditary makeup. One pair of chromosomes is the sex chromosomes, designated X and Y. Females usually have two X chromosomes; however, patients with Turner syndrome have only a single X chromosome or one normal and one defective X or Y chromosome. This abnormality can cause medical problems such as short stature, premature ovarian failure and heart or kidney defects. Individuals with Turner syndrome have an increased risk of thyroid disorders, high blood pressure, diabetes mellitus, abnormal liver function, hearing loss and osteoporosis. This study will try to identify the genes responsible for the specific medical problems associated with the disorder. Females 10 years of age and older with X chromosome defects may be eligible for this 3- to 5- day inpatient study at the National Institutes of Health Clinical Center in Bethesda, Maryland. Participants will have a physical examination, body measurements (height, weight, hip and waist) and blood drawn for clinical and research purposes. Participants will have a comprehensive cardiovascular evaluation, including an electrocardiogram (ECG), 24 hour blood pressure monitoring, magnetic resonance imaging (MRI) of the heart and aorta, ultrasound imaging of the heart (cardiac echo) and expert consultation with the NIH Cardiology Service. Women 35 years of age and older may have a computerized tomography (CT) scan of the coronary arteries to investigate possible blockage of the heart blood supply. Risk for diabetes is investigated by studies of the body fat content and an oral glucose tolerance test. The risk for coronary artery disease is assessed by measurement of cholesterol and other known risk factors in the blood. Thyroid function and presence of antibodies to the thyroid gland are also evaluated by blood tests. Liver function is tested by measurement of products of liver metabolism in the blood and by a liver ultrasound. Ovary function is investigated by blood tests of estrogen and FSH levels and pelvic untrasound which visualizes the uterus. Bone structure and strength are evaluated by routine X-rays of the wrists and spine, and DEXA scan (a type of X-ray study that measures body fat, muscle and bone thickness). Adults will also have bone density of the spine and abdominal fat content measured by CT, which is more accurate than DEXA. Vitamin D levels are measured in blood tests.These are state of the art diagnostic tests which may uncover unsuspected anatomic problems such as abnormalities of the aorta or aortic valve which have serious clinical implications and would indicate the need for close medical follow-up, as well as uncover potential risk for development of diabetes or osteoporosis in the future, which would also indicate the need for changes in lifestyle or medical management. Study participants are invited to return for re-evaluation at 1-3 year intervals. A major goal of follow-up visits is to determine whether there is any enlargement of aortic diameter or impairment of cardiac function over time. Some patients may be asked to undergo a skin biopsy (removal of a small sample of skin tissue) to obtain more information about genetic make-up of cells. Parents of patients may be contacted (with the patient's permission) to provide a blood or saliva sample for genetic study to help understand how and why certain traits of Turner syndrome are expressed.

Conditions

Turner's Syndrome

Keywords

Genes; X-Chromosome; Osteoporosis; Ovarian Failure; Imprinting; Turner's; Turner; TS

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Phenotypic females greater than or equal to 10 years of age
• Evidence of X-chromosomal abnormality
• Those with a karyotype of 45X/46XX must have at least 80% 45X lymphocytes.

You may not qualify if:

• Co-existing autosomal defects
• Pregnancy
• Biological parent of a TS subject
• Willingness to participate
• None

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Bakalov VK, Axelrod L, Baron J, Hanton L, Nelson LM, Reynolds JC, Hill S, Troendle J, Bondy CA. Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency. J Clin Endocrinol Metab. 2003 Dec;88(12):5717-22. doi: 10.1210/jc.2003-030913.

  PMID: 14671158 BACKGROUND

• Hanton L, Axelrod L, Bakalov V, Bondy CA. The importance of estrogen replacement in young women with Turner syndrome. J Womens Health (Larchmt). 2003 Dec;12(10):971-7. doi: 10.1089/154099903322643893.

  PMID: 14709185 BACKGROUND

• Bakalov VK, Chen ML, Baron J, Hanton LB, Reynolds JC, Stratakis CA, Axelrod LE, Bondy CA. Bone mineral density and fractures in Turner syndrome. Am J Med. 2003 Sep;115(4):259-64. doi: 10.1016/s0002-9343(03)00364-4.

  PMID: 12967689 BACKGROUND

• Reimann GE, Bernad Perman MM, Ho PS, Parks RA, Comis LE. Psychosocial Characteristics of Women with a Delayed Diagnosis of Turner Syndrome. J Pediatr. 2018 Aug;199:206-211. doi: 10.1016/j.jpeds.2018.03.058. Epub 2018 May 9.

  PMID: 29753544 DERIVED

• Matura LA, Ho VB, Rosing DR, Bondy CA. Aortic dilatation and dissection in Turner syndrome. Circulation. 2007 Oct 9;116(15):1663-70. doi: 10.1161/CIRCULATIONAHA.106.685487. Epub 2007 Sep 17.

  PMID: 17875973 DERIVED

MeSH Terms

Conditions

Turner Syndrome; Osteoporosis

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Carolyn A Bondy, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 4, 2000
• First Posted: October 5, 2000
• Study Start: September 26, 2000
• Study Completion: July 8, 2014
• Last Updated: October 6, 2017

Record last verified: 2014-07-08

Locations

US (1)