McCune-Albright Syndrome: A Detailed Pathological and Genetic Analysis of Disease Effects in an Adult Patient

Васильев, В. Н.; Daly, Adrian; Thiry, Albert; Pétrossians, Patrick; Fina, Frédéric; Rostomyan, Liliya; Silvy, Monique; Enjalbert, A; Barlier, Anne; Beckers, Albert

doi:10.1210/jc.2014-1291

Cited by 56 publications

(50 citation statements)

References 45 publications

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“…FD may either occur as an isolated condition or as part of the McCune-Albright syndrome (MAS), which is characterized by the following triad: FD, hyperfunctioning endocrinopathies and/or café-au-lait spots. The most common endocrinopathies are precocious puberty, hyperthyroidism, and growth hormone excess (7,8). A sizeable proportion of patients have renal phosphate wasting (9).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Factors From an Epidemiologic Evaluation of Fibrous Dysplasia of Bone in a Modern Cohort: The FRANCEDYS Study

Benhamou

Gensburger

Messiaen

et al. 2016

Journal of Bone and Mineral Research

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Fibrous dysplasia of bone (FD) is a rare genetic but sporadic bone disease that can be responsible for bone pain, fracture, and bone deformity. The prognosis may be difficult to establish because of the wide spectrum of disease severity. We have analyzed the data from the French National Reference center for FD. We have established a database from standardized medical records. We have made descriptive statistics of the various forms of FD and examined the prognostic factors by multivariable logistic regression analysis, with a parsimonious stepwise method. The primary outcome was a clinically relevant composite index combining bone pain (visual analogic scale >3) and/or incident fracture. In our modern cohort of 372 patients, the median age at diagnosis was 23 years. The revealing symptom (at a median age of 18 years) was bone pain in 44% of patients and a fracture in 9%, but the diagnosis was fortuitous in 25% of cases. Monostotic forms represented 58% of patients and polyostotic forms 42%. The femur was the most commonly affected bone (44% of patients), followed by the skull (38%). Twelve percent of patients had McCune-Albright syndrome (MAS). With a median duration of follow-up of 7 years among 211 patients, we observed an incidence of fracture of 17% and 51% of patients had no bone pain at the end of follow-up (with or without bisphosphonate therapy). In univariate analysis, younger age at diagnosis, renal phosphate wasting, a polyostotic form, prevalent fracture, and bisphosphonate use were significant predictors. In the multivariate model, the polyostotic form and bisphosphonate use remained significant predictors. In conclusion, in a national referral center for FD, one patient on follow-up out of six had incident fracture. A polyostotic form was the main risk factor of a poorer outcome. © 2016 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Prognostic Factors From an Epidemiologic Evaluation of Fibrous Dysplasia of Bone in a Modern Cohort: The FRANCEDYS Study

Benhamou

Gensburger

Messiaen

et al. 2016

Journal of Bone and Mineral Research

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“…Examples include verification of point mutations in GCM2 ( glial cells missing homolog 2 ; GCM2(T370M) and GCM2(R367Tfs*) ) associated with hypoparathyroidism [24], in MAP3K3 ( mitogen-activated protein kinase kinase kinase 3 ; MAP3K3(I441M) ) with verrucous venus malformation [25], in PIK3CA (α catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase ; PIK3CA(C420R) , PIK3CA(E542K) , PIK3CA(E545K) , PIK3CA(H1047R) and PIK3CA(H1047L) ) with lympathic malformation and Klippel-Trenaunay syndrome [26], in SMN1 ( SMN1(Y272C) ) with SMA [21] and in GNAS ( stimulatory α subunit of G protein , G s α; GNAS(R201C) ) with McCune-Albright syndrome [27]. In many cases, the disease-associated intragenic mutations were initially identified using next generation sequencing [24], [25], [26].…”

Section: Applications Of Digital Pcr To Pediatric Geneticsmentioning

confidence: 99%

“…In many cases, the disease-associated intragenic mutations were initially identified using next generation sequencing [24], [25], [26]. The disease-associated GNAS mutation associated with McCune-Albright syndrome could not be detected in the patient until after death and only in certain tissues, suggesting somatic mosaicism [27]. With the assistance of a peptide nucleic acid (PNA) oligomer to lower the detection limit, Uchiyama et al [28] can detect low frequency somatic mutations of GNAQ ( G protein α subunit q , G q α; GNAQ(R183Q) ) in patients with Sturge-Weber syndrome, a rare congenital neurocutaneous multisystem disorder, using droplet dPCR.…”

Section: Applications Of Digital Pcr To Pediatric Geneticsmentioning

confidence: 99%

Applicability of digital PCR to the investigation of pediatric-onset genetic disorders

Butchbach

2016

Biomolecular Detection and Quantification

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Early-onset rare diseases have a strong impact on child healthcare even though the incidence of each of these diseases is relatively low. In order to better manage the care of these children, it is imperative to quickly diagnose the molecular bases for these disorders as well as to develop technologies with prognostic potential. Digital PCR (dPCR) is well suited for this role by providing an absolute quantification of the target DNA within a sample. This review illustrates how dPCR can be used to identify genes associated with pediatric-onset disorders, to identify copy number status of important disease-causing genes and variants and to quantify modifier genes. It is also a powerful technology to track changes in genomic biomarkers with disease progression. Based on its capability to accurately and reliably detect genomic alterations with high sensitivity and a large dynamic detection range, dPCR has the potential to become the tool of choice for the verification of pediatric disease-associated mutations identified by next generation sequencing, copy number determination and noninvasive prenatal screening.

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“…The disorder is classically characterized by polyostotic fibrous dysplasia, oral and skin pigmentation (café-au-lait), and peripheral precocious puberty [80 & ]. Additional tissues can be affected including endocrine organs (pituitary, thyroid, and adrenals) and the gastrointestinal tract [81]. Endocrine abnormalities include thyrotoxicosis, pituitary gigantism, and Cushing syndrome.…”

Section: Mosaicsmentioning

confidence: 99%

Proliferation and arrest

Allen¹

2015

Current Opinion in Ophthalmology

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McCune-Albright Syndrome: A Detailed Pathological and Genetic Analysis of Disease Effects in an Adult Patient

Abstract: This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1-related pathology across a wide range of affected organs.

Cited by 56 publications

References 45 publications

Prognostic Factors From an Epidemiologic Evaluation of Fibrous Dysplasia of Bone in a Modern Cohort: The FRANCEDYS Study

Prognostic Factors From an Epidemiologic Evaluation of Fibrous Dysplasia of Bone in a Modern Cohort: The FRANCEDYS Study

Applicability of digital PCR to the investigation of pediatric-onset genetic disorders

Proliferation and arrest

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