ESPE Abstracts (2018) 89 P-P1-193

McCune-Albright-Syndrome: Clinical and Genetic Study in a Large Cohort of Pediatric Patients

Nadezhda Makazan, Elizaveta Orlova, Maria Kareva, Natalia Kalinchenko, Anna Kolodkina, Natalia Zubkova, Evgeniy Vasiliev, Anatoly Tiulpakov & Valentina Peterkova

Endocrinology National Medical Research Center, Moscow, Russian Federation

Background: McCune-Albright-Syndrome (MAS) is an extremely rare multisystem disorder that affects bones (fibrous dysplasia), skin (cafe-au-lait spots) and endocrine organs (hyperfunctioning endocrinopathies) and is caused by somatic mutations in GNAS gene.

Materials and methods: We have evaluated 55 pediatric patients (44 girls (G) and 11 boys (B)) diagnosed in the period of 20 years. Mutation analyses using competitive allele-specific TaqMan PCR (CAST-PCR) and next-generation sequencing (NGS) techniques were performed to search for GNAS mutations in DNA from peripheral leukocytes from 39 MAS patients.

Results: The first clinical manifestation was peripheral precocious puberty in 75% of patients (41/55, G), fibrous dysplasia (FD) – in 20% (11/55, 2G, 9 B) and Cushing’s syndrome (CS) in 3 patients (5%, 3/55, 1 G and 2 B). Peripheral precocious puberty, fibrous dysplasia and Cushing’s syndrome were seen in very young patients in the first months of life. GNAS mutations p.R201C and p.R201H were found in 41% (16/39) of patients with MAS. The prevalence and age of clinical manifestations are shown in Table 1.

Table 1
Clinical manifestations of MAS% of patients (n=55, 44 G+11 B)The age at the time of revealing a clinical finding, y.o.
Fibrous dysplasia78% (43/55)0.9–13
Cafe-au-lait spots84% (46/55)0–3
Girls: peripheral precocious puberty98% (43/44)0.2–4.2
Boys: macroorchidism64% (7/11)1.7–13
Boys: peripheral precocious puberty36% (4/11)3.7–6
Thyropathies (ultrasound)35% (19/55)1.5–13
Hyperthyroidism13% (7/55)1.5–13
Hypophosphatemia33% (18/55)2–13
Growth hormone (GH) excess26% (14/55)4–13
Growth hormone-secreting pituitary adenoma7% (4/55)11.7–13
Cushing’s syndrome9% (5/55)0.4–1
Tachycardia not associated with hyperthyroidism20% (11/55)2.5–13

Conclusion: MAS can manifest in children at the age less than 1 year with precocious puberty in girls, fibrous dysplasia and Cushing’s syndrome. CAST- PCR and NGS methods are not reliable for identifying patients with clinically uncertain MAS.