ESPE Abstracts

Introduction: DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) plays an important role in developing the adrenal gland and testis during embryonic stage. On the other hand, overexpressed DAX1 causes 46,XY disorders of sex development (DSD), in which patients often have short stature, mental retardation, and telecanthus. Here we report a case of 46,Y,dup(X)(p21.2p22.2) DSD caused by overexpressed DAX1.

Case report: Patient was a 3-year-old girl, referred to our hospital for short stature (−2.2 S.D.). Physical examination was as follows; complete female genitalia, low set ears, telecanthus, and cleft palate. Motor and mental development was severely delayed. Chromosome was 46,Y,add(X)(p22.1) and sex-determining region Y (SRY) gene was positive. Diagnosis of DSD was made, and endocrine tests were performed. Serum cortisol level was 7.80 μg/dl (reference range: 5–23), ACTH level was 31.0 pg/ml (reference range: 25–100), 17-OH-progesterone level was 0.33 ng/ml (reference range: 0.3–8.2), LH level was 0.26 mIU/ml (reference range: 0.02–0.3), FSH was 13.26 mIU/ml (reference range: <3.0), serum estradiol level was 19 pg/ml (reference range: 5–11), testosterone level was <0.03 ng/ml (reference range: <0.1), TSH level was 11.8 μIU/ml (reference range: 0.7–6.4), and free T₄ level was 1.15 ng/dl (reference range: 0.8–2.2). In hCG stimulating test, testosterone level did not increase. In TSH stimulating test, TSH level was 315 μU/ml at 30 min, indicating that she had subclinical hypothyroidism. Pelvic MRI did not show ovary, testis, and uterus. Array CGH was performed (Agilent Technology, USA), and duplication was located from p21.1 to p22.2 on X chromosome including DAX1 region. No duplication or deletion existed in any other chromosomes.

Conclusion: This is the first report of overexpressed DAX1 with subclinical hypothyroidism. Although thyroid dysfunction may be coincidental, TSH stimulating test is recommended in such patients in the future.