Turner Syndrome: Genotype and Phenotype

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.