Androgen Effect on Klinefelter Syndrome Motor Outcome

Klinefelter syndrome (KS), a genetic disorder that affects males only, is characterized by
having an extra X chromosome. The phenotype — or physical and learning features — includes
testicular failure, tall stature, and specific cognitive and behavioral attributes such as
diminished motor function, language-based learning difficulties, poor self-image, and
shyness. The KS phenotype may be the result of androgen deficiency in utero, infancy, and
childhood. For individuals with KS, androgen replacement is standard treatment in adolescence
and adulthood but has not been used earlier in childhood or included in the standard medical
care of KS children ages 4 to 12.

The purpose of this study is to examine the effects of androgen on learning and development
in boys with KS. Researchers also want to determine if low-dose androgen replacement at an
early age will improve some of the learning difficulties associated with the disorder. The
overall goal of this study is to address questions regarding the relationship of early
androgen deficiency to learning and motor function.

Participants in the study will be randomized to one of two treatment groups, receiving either
oxandrolone (low-dose androgen) or placebo, for two years. All participants will be evaluated
for safety at the beginning of the study and at 3, 6, 12, 18, and 24 months. Also at the
beginning of the study and every 3 to 6 months thereafter (for a total of 6 visits), the
researchers will perform a careful history and physical examination and a bone age X-ray, and
obtain a blood sample.

Participation in the trial will last two years and includes 6 clinic visits.

Inclusion Criteria:

- Karyotype diagnosis of Klinefelter syndrome

- Chronological age of 4-12 years

- No treatment with androgen in the past year

Exclusion Criteria:

- Major liver, kidney or other systemic disease

- Variant karyotypes including 47,XYY males

- Evidence of spontaneous onset of puberty, defined as testicular size > 4ml