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 Cushings syndrome (CS) in 3 patients (5%, 3/55, 1 G and 2 B). Peripheral precocious puberty, fibrous dysplasia and Cushings 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.
|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 dysplasia||78% (43/55)||0.913|
|Cafe-au-lait spots||84% (46/55)||03|
|Girls: peripheral precocious puberty||98% (43/44)||0.24.2|
|Boys: macroorchidism||64% (7/11)||1.713|
|Boys: peripheral precocious puberty||36% (4/11)||3.76|
|Thyropathies (ultrasound)||35% (19/55)||1.513|
|Growth hormone (GH) excess||26% (14/55)||413|
|Growth hormone-secreting pituitary adenoma||7% (4/55)||11.713|
|Cushings syndrome||9% (5/55)||0.41|
|Tachycardia not associated with hyperthyroidism||20% (11/55)||2.513|
Conclusion: MAS can manifest in children at the age less than 1 year with precocious puberty in girls, fibrous dysplasia and Cushings syndrome. CAST- PCR and NGS methods are not reliable for identifying patients with clinically uncertain MAS.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology