Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center

IntroductionMcCune-Albright syndrome (MAS) is a rare disease caused by somatic gain-of-function variants in the GNAS gene that lead to constitutive activation of the G protein alpha subunit (Gsα). Pathologic consequences can involve several tissues. Fibrous dysplasia (FD), café-au-lait skin macules...

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Main Authors: Solène Bergignat, Roland Chapurlat, Marc Nicolino, Kevin Perge
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1531765/full
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author Solène Bergignat
Roland Chapurlat
Roland Chapurlat
Roland Chapurlat
Marc Nicolino
Marc Nicolino
Kevin Perge
Kevin Perge
author_facet Solène Bergignat
Roland Chapurlat
Roland Chapurlat
Roland Chapurlat
Marc Nicolino
Marc Nicolino
Kevin Perge
Kevin Perge
author_sort Solène Bergignat
collection DOAJ
description IntroductionMcCune-Albright syndrome (MAS) is a rare disease caused by somatic gain-of-function variants in the GNAS gene that lead to constitutive activation of the G protein alpha subunit (Gsα). Pathologic consequences can involve several tissues. Fibrous dysplasia (FD), café-au-lait skin macules and hyperfunctioning endocrinopathies are classic manifestations. However, the phenotypic spectrum of MAS is considerably wider and more complex.MethodsWe performed a pediatric retrospective study from our National Referral Center between 2007 and 2021 to describe the clinical spectrum of MAS in children, with a focus on unusual or severe manifestations.Results and discussionA total of 33 children were included. Peripheral precocious puberty was the most frequent endocrinopathy, affecting 84,6% of girls and was the presenting feature for 57,6% of them. Thyroid involvement was also common, consisting in morphological abnormalities with or without slight hyperthyroidism. Thyroid nodules were typically benign, but one patient presented a follicular thyroid carcinoma. Cushing syndrome typically occurs in the neonatal period, but we observed an unusual case of hypercortisolism revealed in early infancy. FD was very common and manifested along a wide range of severity, from monostotic and asymptomatic lesion to polyostotic FD with pain, fractures, and compressive optic neuropathy. We described a locally aggressive FD involving sphenoid and maxillary bones which leaded a young female patient to death. Finally, we reported hepatic disorders, including a case of hepatocellular adenoma. In conclusion, MAS is a multisystemic disorder, with a variable combination of symptoms, and a broad range of severity. These uncommon abnormalities mostly occurred in patients with significant involvement of multiple other tissues.
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spelling doaj-art-63391d0ff54448efa90410f459d1065e2025-08-20T02:04:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-02-011610.3389/fendo.2025.15317651531765Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral CenterSolène Bergignat0Roland Chapurlat1Roland Chapurlat2Roland Chapurlat3Marc Nicolino4Marc Nicolino5Kevin Perge6Kevin Perge7Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d’Endocrinologie Pédiatrique et Pédiatrie Générale, Bron, FranceFaculté de Médecine Lyon-Est, Université Claude Bernard, Lyon, Lyon, FranceHospices Civils de Lyon, Hôpital Edouard-Herriot, Service de rhumatologie, Lyon, FranceCentre National de Référence de la Dysplasie Fibreuse des Os, Hôpital E Herriot, Lyon, FranceHospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d’Endocrinologie Pédiatrique et Pédiatrie Générale, Bron, FranceFaculté de Médecine Lyon-Est, Université Claude Bernard, Lyon, Lyon, FranceHospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d’Endocrinologie Pédiatrique et Pédiatrie Générale, Bron, FranceFaculté de Médecine Lyon-Est, Université Claude Bernard, Lyon, Lyon, FranceIntroductionMcCune-Albright syndrome (MAS) is a rare disease caused by somatic gain-of-function variants in the GNAS gene that lead to constitutive activation of the G protein alpha subunit (Gsα). Pathologic consequences can involve several tissues. Fibrous dysplasia (FD), café-au-lait skin macules and hyperfunctioning endocrinopathies are classic manifestations. However, the phenotypic spectrum of MAS is considerably wider and more complex.MethodsWe performed a pediatric retrospective study from our National Referral Center between 2007 and 2021 to describe the clinical spectrum of MAS in children, with a focus on unusual or severe manifestations.Results and discussionA total of 33 children were included. Peripheral precocious puberty was the most frequent endocrinopathy, affecting 84,6% of girls and was the presenting feature for 57,6% of them. Thyroid involvement was also common, consisting in morphological abnormalities with or without slight hyperthyroidism. Thyroid nodules were typically benign, but one patient presented a follicular thyroid carcinoma. Cushing syndrome typically occurs in the neonatal period, but we observed an unusual case of hypercortisolism revealed in early infancy. FD was very common and manifested along a wide range of severity, from monostotic and asymptomatic lesion to polyostotic FD with pain, fractures, and compressive optic neuropathy. We described a locally aggressive FD involving sphenoid and maxillary bones which leaded a young female patient to death. Finally, we reported hepatic disorders, including a case of hepatocellular adenoma. In conclusion, MAS is a multisystemic disorder, with a variable combination of symptoms, and a broad range of severity. These uncommon abnormalities mostly occurred in patients with significant involvement of multiple other tissues.https://www.frontiersin.org/articles/10.3389/fendo.2025.1531765/fullMcCune-Albright syndromeGNASprecocious pubertyacromegalythyroid carcinomaCushing syndrome
spellingShingle Solène Bergignat
Roland Chapurlat
Roland Chapurlat
Roland Chapurlat
Marc Nicolino
Marc Nicolino
Kevin Perge
Kevin Perge
Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
Frontiers in Endocrinology
McCune-Albright syndrome
GNAS
precocious puberty
acromegaly
thyroid carcinoma
Cushing syndrome
title Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
title_full Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
title_fullStr Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
title_full_unstemmed Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
title_short Clinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center
title_sort clinical spectrum and uncommon features of mccune albright syndrome in children a cohort study from a national referral center
topic McCune-Albright syndrome
GNAS
precocious puberty
acromegaly
thyroid carcinoma
Cushing syndrome
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1531765/full
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