McCune-Albright Syndrome is a rare genetic disorder characterized by triad of polyostotic fibrous dysplasia of bone, precocious puberty and café au lait skin pigmentation. It is resulted from an activating mutation in the GNAS gene encoding the alpha subunitof stimulatory G protein. Here we present two cases with McCune Albright syndrome presenting with different clinical findings.
Case 1: A 7-year and 6 month-old girl presented with breast development beginning 7 months ago. Her height was 129 cm (93p),on physical examination her breasts were consistent with Tanner stage 4, without axillary and pubic hair. She didnt have any caffe au lait spot. Her bone age was 10 years, basal LH<0.1 mIU/ml, estradiol<5 pg/ml, pelvic USG showed enlarged ovaries (right 29 ml, left over 22 ml) and numerous follicles. It was learnt that a large number of cysts were seen in both ovaries on the prenatal ultrasound, and ovary cysts were aspired on postnatal day 5 as she had an ovarian hyperstimulation syndrome. Numerous variants in the GNAS gene were detected by whole exome sequencing performed in the ovarian biopsy material, however no mutation was detected in the GNAS gene in peripheral blood cells. Her other hormone tests were normal. Fulvestrane treatment was started in order to control pubertal progression.Case 2: A 9-year and 11 month- old girl presented with vaginal bleeding. Her height was 149 cm (96p), development of breast was consistent with Tanner stage 4-5 and pubic hair was consistent with stage 4. There were a lot of nevus on her face and body but no caffe au lait spot. The bone age was 13 years, serum estradiol: 92 pg/ml, LH:0.18 mIU/ml, pelvic USG revealed enlarged ovaries (right:11.8 cc, left:37 cc) with many cysts. X-Ray revealed subcortical frosted glass densities in the left radius and right tibia, scintigraphy showed that these lesions were consistent with fibrous dysplasia. GNAS gene analysis of the case is pending. Tamoxifen treatment was started.
Conclusion: The absence of mutation in the GNAS gene in peripheral blood does not exclude the diagnosis of McCune Albright syndrome because of the mosaic/heterogeneous nature of this syndrome. The diagnosis is mainly based on clinical findings.The presence of multiple ovarian cysts and asymmetric enlargement of one ovary should suggest McCune Albright syndrome, even if there is no other feature such as caffe au lait spots and fibrous dysplasia.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology