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Extent of Extraskeletal Manifestations of Fibrous Dysplasia/McCune-Albright Syndrome in Patients with Mazabraud’s Syndrome

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Abstract

Mazabraud’s syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the GNAS-mutation. Recent studies have shown that extraskeletal, GNAS-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hôpital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or café-au-lait patches (CAL) were retrieved from patient’s medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16–19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0–60), p < 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (n = 7), CAL (n = 7), GH-excess (n = 3) and hyperthyroidism (n = 3) were present. Other extraskeletal features were (multinodular) goiter (n = 2) and thyroid cysts (n = 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal GNAS-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal GNAS features of FD/MAS.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to privacy legislation but are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This research was funded in part by the Intramural Research Program of the NIH, NIDCR. M. Hagelstein-Rotman and B.C.J. Majoor were supported by a grant from the Bontius Foundation, ‘Beter Bot’.

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Authors and Affiliations

  1. Department of Medicine: Division of Endocrinology, Centre for Bone Quality, Leiden University Medical Center, Leiden, the Netherlands

    M. Hagelstein-Rotman & N. M. Appelman-Dijkstra

  2. Department of Orthopaedic Surgery, Centre for Bone Quality, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, the Netherlands

    M. Hagelstein-Rotman, N. B. J. Dur, B. C. J. Majoor, M. A. J. van de Sande & P. D. S. Dijkstra

  3. Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    A. M. Boyce

  4. UMR 1033, INSERM, University of Lyon, Hôpital Edouard Herriot, Lyon, France

    R. Chapurlat & D. Gensburger

Authors
  1. M. Hagelstein-Rotman
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  2. N. M. Appelman-Dijkstra
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  3. A. M. Boyce
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  4. R. Chapurlat
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  5. N. B. J. Dur
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  6. D. Gensburger
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  7. B. C. J. Majoor
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  8. M. A. J. van de Sande
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  9. P. D. S. Dijkstra
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Contributions

MHR was involved in acquisition, analysis and interpretation of the data and in drafting the manuscript. NMA-D was involved in acquisition, analysis and interpretation of the data and in drafting the manuscript. AMB was involved in analysis and interpretation of the data and in drafting the manuscript. RC was involved in analysis and interpretation of the data and in drafting the manuscript. NBJD was involved in acquisition, analysis and interpretation of the data and in drafting the manuscript. DG was involved in analysis and interpretation of the data and in drafting the manuscript. BCJM was involved in interpretation of the data and in drafting the manuscript. MAJS was involved in interpretation of the data and in drafting the manuscript. PDSD was involved in interpretation of the data and in drafting the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to M. Hagelstein-Rotman.

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The authors declare that they have no competing interests.

Ethical Approval

The protocol was approved by the Medical Ethics Committee of the LUMC.

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Consent for publication was obtained from patiens whose individual details and images were used in this manuscript.

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Hagelstein-Rotman, M., Appelman-Dijkstra, N.M., Boyce, A.M. et al. Extent of Extraskeletal Manifestations of Fibrous Dysplasia/McCune-Albright Syndrome in Patients with Mazabraud’s Syndrome. Calcif Tissue Int 110, 334–340 (2022). https://doi.org/10.1007/s00223-021-00918-0

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  • DOI: https://doi.org/10.1007/s00223-021-00918-0

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