Clinical and endocrine characteristics and genetic analysis of Korean children with McCune–Albright syndrome: a retrospective cohort study

Abstract

BackgroundMcCune–Albright syndrome (MAS) is a rare disease defined by the triad of fibrous dysplasia (FD), café au lait spots, and peripheral precocious puberty (PP). Because of the rarity of this disease, only a few individuals with MAS have been reported in Korea. We describe the various clinical and endocrine manifestations and genetic analysis of 14 patients with MAS in Korea.MethodsPatients’ clinical data—including peripheral PP, FD, and other endocrine problems—were reviewed retrospectively. In addition, treatment experiences of letrozole in five patients with peripheral PP were described. Mutant enrichment with 3′-modified oligonucleotides - polymerase chain reaction (MEMO-PCR) was performed on eight patients to detect mutation in GNAS using blood. MEMO-PCR is a simple and practical method that enables the nondestructive selection and enrichment of minor mutant alleles in blood.ResultsThe median age at diagnosis was 5 years 2 months (range: 18 months to 16 years). Eleven patients were female, and three were male. Thirteen patients showed FD. All female patients showed peripheral PP at onset, and three patients subsequently developed central PP. There was a significant decrease in estradiol levels after two years of letrozole treatment. However, bone age was advanced in four patients. Two patients had clinical hyperthyroidism, and two patients had growth hormone (GH) excess with pituitary microadenoma. c.602G > A (p.Arg201His) in GNAS was detected in two patients in blood, and c.601C > T (p.Arg201Cys) in GNAS was detected in one patient in pituitary adenoma.ConclusionsThis study described the various clinical manifestations of 14 patients with MAS in a single center in Korea. This study first applied MEMO-PCR on MAS patients to detect GNAS mutation. Because a broad spectrum of endocrine manifestations could be found in MAS, multiple endocrinopathies should be monitored in MAS patients. Better treatment options for peripheral PP with MAS are needed.

Auxological and Endocrinological Features in Children With McCune Albright Syndrome: A Review

“…FD is the most frequent feature in MAS and it is often accompanied by extraskeletal manifestations ( 3 , 6 ). Only a small percentage of cases manifests in the absence of any FD ( 6 , 7 ). Diagnosis of MAS is most often established in early childhood, but it may occur at birth due to the presence of CALMs ( 6 ).…”

Using Digital Droplet Polymerase Chain Reaction to Detect the Mosaic GNAS Mutations in Whole Blood DNA or Circulating Cell-Free DNA in Fibrous Dysplasia and McCune-Albright Syndrome

“…The patients included 16 females and 1 male, comprising 12 children (average age 6.5 We compared the performance of the 2 strategies, one using ddPCR™ on whole blood DNA alone and the other using ddPCR™ on whole blood DNA plus ccfDNA, with the performance of the four published methods ( Table 4; 11,[18][19][20][21][22]. Despite the small number of patients in our series, the number of ddPCR™ diagnoses, was higher than those using nested-PCR (p<0.05; Table 4).…”

“…For several years, teams have been developing molecular methods more sensitive than Sanger sequencing to detect rare molecular events in peripheral blood leukocytes DNA, such as the R201H and R201C GNAS mutant alleles in FD/MAS. These methods, nested-PCR, PNA clamping, PCR and MEMO-PCR are based on the enrichment of the mutant allele vs. the WT by enzymatic digestion or by masking the WT allele (11,20,21,26 Table 4). The ddPCR TM performance in patients with only 1 or 2 signs of DF/MAS is particularly promising in comparison to the other methods.…”

“…MAS diagnosis is based on clinical features, but the time lag between the first sign (often PPP at an average of 3 to 4 years old) and the others leads to an important delay of clinical diagnosis (10,11). A molecular diagnosis could allow an earlier diagnosis and consequently a follow-up and a therapeutic choice more adapted to the FD/MAS context, reducing the complications and optimizing the quality of life.…”

Treatment of precocious puberty in a McCune–Albright syndrome patient using Chinese medicinal herbs combined with megestrol acetate: A case report

“…13,19 In our case, the GNAS was not detected maybe because the mutation abundance is generally low in unaffected tissues, as some researches have found. 20 In this case, we chose the therapy of Chinese medicinal herbs combined with megestrol acetate. The prescription of Chinese medicinal herbs was composed of Fructus Hordei Germinatus, Radix Rehmanniae, Radix Scrophulariae, Rhizoma Alismatis, Rhizoma Anemarrhenae, Cortex Phellodendri, Carapax et Plastrumtestudinis, and Cortex Moutan (Table 1).…”