Effect of Growth Hormone on Early Brain Development in Girls With Turner Syndrome

The purpose of this research study is to learn about brain development in very young girls with Turner syndrome (TS) and the effect that growth hormone (GH) therapy has on early brain development.

Studies in older children and adults have found that IQ (intelligence quotient) in individuals with Turner syndrome (TS) and the general population are similar. However, many individuals with TS have a nonverbal learning disability which may cause problems with imagining and working with objects in space (for example: building blocks, working puzzles, copying designs, driving a car) as well as problems in planning, paying attention, and getting along with people their own age. Studies of brain structure have found changes in the size and function of specific areas of the brain that are involved in these nonverbal processes. However, there are no data published on brain structure or function in girls with Turner Syndrome in the first few years of life when brains are learning and growing most rapidly. In a recent study, very young, short girls with Turner Syndrome (TS)(averaging 2 years in age) were treated with Growth Hormone (GH) and almost reached an average height after 2 years. The risks of GH for the young girls in that study appeared to be the same as those for older girls. Therefore, it is now recommended that GH therapy be considered as soon as a child with TS has growth failure. Growth failure often occurs during infancy; therefore, more children with TS are now receiving GH therapy as young as 12 months of age. In this study, the investigators wish to start understanding what effect GH has on learning and brain growth when given between the ages of 12 and 24 months. In this study, the girls with TS will have developmental studies, a physical examination, magnetic resonance imaging (MRI), and blood drawn at one and two years of age. Some of the girls in this study will receive GH from 12 until 24 months of life, while others will not. Brain growth and development will be compared between those who have been treated with GH and those who have not. This is a pilot study in which the investigators will gather data to design a larger study that can answer these questions.

Subjects in the somatotropin (growth hormone, GH) arm will receive GH injections from 12-24 months of life.

Subjects will receive 5 mg somatotropin (growth hormone) pens with cartridges. Subcutaneous injections are to be given every evening around bedtime. Dosing regimen: 50 mcg/kg/day to be adjusted at 4 month intervals to the closest 0.1 mg. Subjects will be given 12 months of treatment (from 12 to 24 months of life). Subjects will visit their pediatrician or pediatric endocrinologist at 4 and 8 months of life.

Change in the fractional anisotropy (FA) of white matter tracts using Diffusion Tensor Imaging (DTI); superior longitudinal fasciculus

Percent change in volumes of central brain region (precentral gyrus, postcentral gyrus, rolandic operculum) as determined by MRI.

Inclusion Criteria: Diagnosis of Turner syndrome Less than the 50th percentile for length for the general female population Exclusion Criteria: Prior Growth Hormone (GH) therapy Diabetes Allergy to metacresol (a preservative in the GH liquid that is injected) Contraindications for Magnetic Resonance Imaging (MRI) (such as metal in the body) Part of a Y chromosome in child's karyotype Parent/guardian is not willing for child to be randomized to be in the treatment group (receives Growth Hormone injections for one year) or the control group (receives no Growth Hormone during the study) Parent/guardian is not willing for child to have some of her developmental testing digitally recorded for scoring