ESPE Abstracts

Introduction: McCune Albright Syndrome (MAS) is a rare disorder caused by somatic activating mutations of the GNAS gene, characterized by monostotic/polyostotic fibrous dysplasia, café au lait skin pigmentation and hyperfunctioning endocrinopathies. We report a case of MAS presenting with mild phenotypic characteristics and central precocious puberty (CPP).

Case: Indian female was referred to our clinic for premature thelarche. Second child, born at term by caesarean section due to foetal abnormal presentation. Pregnancy was physiological, parents were non consanguineous. Neonatal weight was 2678 g (-0.85 SDS). At birth a congenital vascular abnormality on the nose was treated with propranolol for 9 months. At first evaluation at the age of 1 year and 10 months length was 80.3 cm (-1.45 SDS), within the family range (target height 155 cm, -1.3 SDS), weight was 9.9 kg (-0.96 SDS), head circumference was 45.5 cm (-1.03 SDS). Puberal stages showed bilateral thelarche (B2), no pubarche. Bone age was correspondent to chronological age according with Greulich &Pyle atlas. Initial blood exams and pelvic ultrasound were compatible with prepuberty. Due to persistent thelarche and increased height velocity, the girl underwent a gonadotropin-releasing hormone (GnRH) stimulation test that confirmed CPP. Brain MRI was normal. Therapy with a GnRH agonist was started. Due to the discovery of a widespread café-au-lait spot on the left side of the abdomen and two other millimetric spots on the right side of the abdomen and left arm, with indented edges (not compatible with neurofibromatosis 1), genetic evaluation was requested. In the suspicion of a somatic mosaicism of the GNAS gene, digital PCR analysis was performed, both on DNA extracted from peripheral blood leukocytes and on circulating DNA extracted from plasma, revealing the variant c.605G>A in the GNAS gene. This variant, compatible with MAS, is present only in some cells (mosaicism) and appeared in the post-zygotic phase. Parents were not carriers of this variant. Other investigations were precociously performed according to guidelines; currently no other endocrinopathies have been found and no radiological bone abnormalities have been detected.

Discussion: MAS is characterised by a variable spectrum of phenotypes. Our patient presented a mild phenotype, probably due to mosaicism and early timing of diagnosis. Interestingly, the girl presented gonadotropin-dependent and not gonadotropin-independent PP, that is most frequently associated with the syndrome. Precocious diagnosis was essential to start specific follow-up of the patient, allowing clinicians to promptly identify and eventually treat any other manifestations or complications.