Hagelstein-Rotman M, Appelman-Dijkstra N M, Boyce A M, Chapurlat R, Dur N B J, Gensburger D, Majoor B C J, van de Sande M A J, Dijkstra P D S
Department of Medicine: Division of Endocrinology, Centre for Bone Quality, Leiden University Medical Center, Leiden, the Netherlands.
Department of Orthopaedic Surgery, Centre for Bone Quality, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, the Netherlands.
Calcif Tissue Int. 2022 Mar;110(3):334-340. doi: 10.1007/s00223-021-00918-0. Epub 2021 Dec 2.
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.
马扎布罗德综合征（MZB）是一种罕见病症，其中骨纤维发育不良/麦库恩-奥尔布赖特综合征（FD/MAS）与肌内黏液瘤并存。FD和黏液瘤均存在GNAS突变。最近的研究表明，骨骼外的、与GNAS相关的特征与FD/MAS更严重的表型相关。然而，MZB患者通常仅由骨科医生诊治。因此，我们评估了来自荷兰（鹿特丹大学医学中心）、美国（国立卫生研究院）和法国（国家科研中心UMR 1033（利奥斯）、爱德华·赫里奥特医院）的三级转诊中心诊治的MZB患者。纳入了这些中心所有已知患有FD/MAS且额外诊断出黏液瘤的患者。从患者病历中获取人口统计学信息以及关于FD/MAS疾病范围和骨骼外表现的数据，如性早熟（PP）或咖啡牛奶斑（CAL）。共纳入30例MZB患者：20例女性（67%）和10例男性（33%）。MZB患者确诊时（中位年龄42岁，范围16 - 19岁）明显晚于FD/MAS确诊时（中位年龄30岁，范围0 - 60岁），p < 0.01。26例患者被诊断为多骨型疾病（87%）。97%的黏液瘤位于骨骼FD病变附近。13例患者同时患有MZB和MAS，其中存在PP（n = 7）、CAL（n = 7）、生长激素过多（n = 3）和甲状腺功能亢进（n = 3）。其他骨骼外特征包括（多结节性）甲状腺肿（n = 2）和甲状腺囊肿（n = 1）。此外，在这组MZB患者中观察到了几种（前）恶性肿瘤；3例患者（10%）患有乳腺导管原位癌，1例患者（3.3%）患有乳腺癌，3例患者（10%）患有胰腺内黏液性肿瘤，2例患者（6.6%）患有肝腺瘤。共有47%的MZB患者有额外的骨骼外特征，如内分泌病。在MZB中，87%的患者患有多骨型FD，43%的患者有骨骼外GNAS特征，如内分泌功能亢进，30%的患者患有（前）恶性肿瘤。因此，我们主张MZB患者应接受全面筛查，并对骨病范围以及FD/MAS的骨骼外GNAS特征进行长期随访。
