Patient case (clinical description): A 3-year-old girl is brought to the clinic by her parents for assessment of her short stature. Physical examination reveals short limbs and a relatively large head. She has a flat nasal bridge and a small midface. The girl's father exhibits similar physical features; however, her mother looks normal. The genetic testing reveals an autosomal dominant point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene consistent with achondroplasia in both father and the child. The girl has not received any treatment yet, and it is her first visit after immigration to the US. The other mental and developmental examinations are unremarkable.

Patient's own account: I just brought my little 3-year-old girl to the clinic to have her checked up by the doctor. I was worried sick because she was smaller than her classmates. The lovely doctor performed a physical exam and she told me that she has short limbs and a larger head. My girl also has a flat nasal bridge and a small midface. My baby just has the face of her father, unlike me! They performed some genetic testing on my child and my husband and found out that both my husband and her have a mutation of the FGFR3 gene, which led the doctor to diagnose them with dwarfism. My baby never received any treatment and it was our first visit to the doctor since we arrived in the US. The other tests regarding her mental and physical development were perfectly fine.

Clinical trial: Ovarian Contribution to Androgen Production in Adolescent Girls

Eligibility criteria:
Inclusion Criteria:

          -  Girls age 7-18 years

          -  Normal weight (BMI 5-85%-ile for age) or overweight (>85%-ile)

          -  With or without signs of excess androgen

          -  Screening labs within age-appropriate normal range, with the exception of a mildly low
             hematocrit (see below) and the hormonal abnormalities inherent in obesity which could
             include mildly elevated luteinizing hormone (LH), lipids, testosterone, prolactin,
             DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH)
             and/or sex hormone-binding globulin (SHBG)

        Exclusion Criteria:

          -  Patients currently enrolled in another research protocol will be excluded, except for
             those enrolled in IRB-HSR #12702/JCM022. This protocol is designed to allow subjects
             enrolling in IRB-HSR #12702/JCM022 to simultaneously participate in this companion
             protocol.

          -  Inability to comprehend what will be done during the study or why it will be done

          -  BMI-for-age < 5th percentile

          -  Weight < 27 kg if simultaneously participating in IRB-HSR #12702/JCM022 due to blood
             volume limits

          -  Obesity associated with a diagnosed genetic syndrome (e.g. Prader-Willi syndrome)

          -  Since the study involves looking at ovarian function, boys will be excluded.

          -  Positive pregnancy test or lactation. Subjects with a positive pregnancy test will be
             informed of the result by the screening physician. Under Virginia law, parental
             notification is not required for minors. However, the screening physician will
             encourage them to tell their parent(s) and counsel them about the importance of
             appropriate prenatal care and counseling. We will arrange follow-up for them at the
             Teen Health Clinic at the University of Virginia or their primary care physician's
             office in a timely manner.

          -  Abnormal laboratory studies will be confirmed by repeat testing to exclude laboratory
             error.

          -  Morning cortisol < 3 microgram/dL or history of Cushing syndrome or adrenal
             insufficiency

          -  History of congenital adrenal hyperplasia or 17-hydroxyprogesterone > 300 ng/dL, which
             suggests the possibility of congenital adrenal hyperplasia (if postmenarchal, the
             17-hydroxyprogesterone will be collected during the follicular phase, or ≥ 40 days
             since last menses if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone >300 mg/dL is
             confirmed on repeat testing, an adrenocorticotropic hormone-stimulated
             17-hydroxyprogesterone <1000 ng/dL will be required for study participation.

          -  Total testosterone > 150 ng/dL

          -  Previous diagnosis of diabetes, fasting glucose ≥126 mg/dL, or a hemoglobin A1c >6.5%

          -  Abnormal thyroid stimulating hormone (TSH) for age. Subjects with adequately treated
             hypothyroidism, reflected by normal TSH values, will not be excluded.

          -  Abnormal prolactin. Mild elevations may be seen in overweight girls, and elevations
             <1.5 times the upper limit of normal will be accepted in this group.

          -  Persistent hematocrit <36% and hemoglobin <12 g/dL. Subjects with a mildly low
             hematocrit (33-36%) will be asked to take iron in the form of ferrous gluconate for up
             to 60 days. Subjects weighing ≤ 36 kg will take one 300-325 mg tablet oral ferrous
             gluconate daily (containing 36 mg elemental iron); subjects weighing >36 kg will take
             two 300-325 mg tablets oral ferrous gluconate daily (containing 36 mg elemental iron
             each). They will return to the Clinical Research Unit (CRU) or alternate UVA clinical
             unit after 30-60 days of iron therapy to have their hemoglobin or hematocrit rechecked
             and will proceed with the remainder of the study if it is ≥12 g/dL or ≥36%,
             respectively.

          -  Persistent liver test abnormalities, with the exception that mild bilirubin elevations
             will be accepted in the setting of known Gilbert's syndrome. Mild elevations may be
             seen in overweight girls, so elevations <1.5 times the upper limit of normal will be
             accepted in this group.
Female
Accepts Healthy Volunteers
Subject must be at least 7 Years old.
Subject must be at most 18 Years

Eligibility (NLI label): Contradiction