McCune-Albright综合征

McCune-Albright综合征是一种少见的G蛋白病,临床以性早熟、多发性骨纤维异常增殖症及皮肤斑片状色素沉着为最常见的症状,病因是在胚胎形成过程中的鸟嘌呤核苷酸结合蛋白(G蛋白)α亚基(Gsα)基因的突变,导致刺激cAMP产生可激活许多内分泌激素的受体。治疗主要是对症治疗,尚无有效根治方法。该文报道3例该病病例,并复习了相关文献。这3例病例均出现多发性骨纤维异常增殖症、性早熟及咖啡色色素斑典型的三联征而确诊。     

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.     

Pamidronate treatment of polyostotic fibrous dysplasia: failure to prevent expansion of dysplastic lesions during childhood

AIMS: To examine outcomes of pamidronate treatment on fibrous dysplasia of bone in three children with McCune-Albright syndrome (MAS). METHODS: Radiological evidence of fibrous dysplasia progress was reviewed for three children with MAS who were treated with pamidronate from age 2.5-5 years, for 8-10.5 years. RESULTS: Despite minimal pain and a low fracture rate in long bones, except where gross deformity exists, all dysplastic lesions present in long bones continued to undergo uncontrolled expansion. In contrast, there were no major new changes in facial configuration, no clinically obvious expansion of sphenoid wing lesions and no encroachment on optic foramina or visual field restriction in any patient. CONCLUSIONS: Despite previous reports of limitation or reduction in size of fibrous dysplasia lesions in adults and children, it is our experience that bisphosphonate treatment of polyostotic fibrous dysplasia in children with MAS does not arrest the expanding nature of these lesions.     

Imaging of McCune-Albright syndrome using bone single photon emission computed tomography

McCune-Albright syndrome is a rare disorder caused by a somatic, constitutively activating mutation in the gene (GNAS1) encoding the subunit of the signal transducing guanine nucleotide binding protein (G protein). The condition is characterized by polyostotic fibrous dysplasia, cafe-au-lait pigmentation and multiple endocrine hyperfunction, most commonly gonadotropin-independent precocious puberty in girls. Our patient, a 16-year-old male, with radiologically confirmed polyostotic fibrous dysplasia in cranium, thoracic and pelvic girdles, spine and extremities was studied using planar ^99mTc-hydroxymethyldiphosphonate bone scintigraphy and single photon emission computed tomography. Using bone scintigraphy, an unusually extensive and asymmetric fibrous dysplasia was observed in the cranium, face, ribs, femur, humerus, ulna, tibia and the vertebral column, all on the left side. The whole body scan revealed only a few foci on the right side. Single photon emission computed tomography demonstrated extensive unilateral involvement in the base of the skull, facial bones, maxilla and mandible. All the lesions reached only the midline. These findings formed the basis of further treatment, eg. reconstructive surgery of facial asymmetry. Conclusion McCune-Albright syndrome should be considered in the differential diagnosis when interpreting extensive unilateral predominance in paediatric bone scans. Received: 3 March 1998 / Accepted in revised form: 19 May 1998     

Epidermal naevus syndrome associated with polyostotic fibrous dysplasia and central precocious puberty

We report a boy with the epidermal naevus syndrome, hemimegalencephaly and central precocious puberty who also had polyostotic fibrous dysplasia and skin pigmentation similar to that seen in the McCune-Albright Syndrome.     

The McCune-Albright syndrome without typical skin pigmentation

This paper describes three girls with an incomplete form of the McCune-Albright syndrome. Polyostotic fibrous dysplasia and precocious puberty were present but the typical abnormal skin pigmentation was absent.     

Acrogigantism and facial asymmetry: McCune-Albright syndrome

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery.     

THE McCUNE-ALBRIGHT SYNDROME WITHOUT TYPICAL SKIN PIGMENTATION

ABSTRACT. This paper describes three girls with an incomplete form of the McCune-Albright syndrome. Polyostotic fibrous dysplasia and precocious puberty were present but the typical abnormal skin pigmentation was absent.     

Cushing's syndrome caused by nodular adrenal hyperplasia in children with McCune-Albright syndrome.

McCune-Albright syndrome consists of fibrous dysplasia of bone, café-au-lait skin pigmentation, and endocrine dysfunction (usually precocious puberty). Other endocrine abnormalities occur in a minority of patients, and of these, Cushing's syndrome is the least often recognized. We present 5 children (4 girls) with features of McCune-Albright syndrome who had Cushing's syndrome in the infantile period (<6 months). In 2 children spontaneous resolution occurred, but the remaining 3 required bilateral adrenalectomy. In addition, all 4 girls have experienced precocious puberty, and 3 children demonstrated radiologic evidence of nephrocalcinosis. Understanding of the underlying defect causing McCune-Albright syndrome emphasizes the importance of searching for other endocrine dysfunction in these children.     

Bisphosphonate therapy for fibrous dysplasia

Bony fibrous dysplasia is one of the hallmark features of McCune-Albright syndrome. Fibrous dysplasia can result in pain, fracture and deformity in affected areas. A number of observational, uncontrolled reports have been published outlining results of bisphosphonate therapy for fibrous dysplasia. Bisphosphonates are well tolerated and appear to be useful for reducing bone pain. Although their use is also associated with decreases in bone turnover, increases in bone density and radiological changes, their impact on the overall course of the disease, particularly the incidence of fractures and deformity, is less clear. Many questions remain about optimizing their use for fibrous dysplasia therapy.     

An extensive type of polyostotic fibrous dysplasia

The case describes an 11-year-old girl affected by an unusually extensive type of polyostotic fibrous dysplasia. The cranium and face and both femurs, tibias, and fibulas were extensively and almost symmetrically involved. Tubulation deformities were noted in the metacarpals and middle phalanges of both hands. These findings appear to represent a very severe manifestation of the disease, as polyostotic fibrous dysplasia is known to be predominantly unilateral. The patient had endocrine dysfunction consistent with McCune-Albright syndrome. Radiological work-up included plain radiography of the skeleton and CT, MR imaging, and MR angiography of the cranium. Accepted: 12 January 1996     

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.     

Clinical, endocrinological and radiography features in a child with McCune-Albright syndrome and pituitary adenoma

McCune-Albright syndrome is a rare syndrome presenting with polyostotic dysplasia, cafe-au-lait spots and multiple endocrinopathies that is very often combined with precocious puberty. We examined the clinical, endocrinological and radiological features in a boy with McCune-Albright syndrome and pituitary adenoma. X-rays, magnetic resonance (MRI) scan, whole body scintigraphy, single photon emission computer tomography (SPECT) and 3D-reconstruction from bone SPECT was performed to evaluate clinical improvement after treatment with sandostatin and pamidronic acid. After a six-month period of treatment with sandostatin and pamidronate, bone scintigraphy revealed significantly reduced activity. Treatment with bromocriptine and methimazole led to normalization of prolactin and thyroid hormone levels. Mobility of the patient improved. A significant improvement as a result of treatment with sandostatin and pamidronic acid was found in this patient with generalized fibrous dysplasia. So far, this condition has been treated with pamidronate only in adults, but severely affected children also benefit from this treatment regimen.     

Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?

OBJECTIVE: McCune-Albright syndrome (MAS) is characterized by a clinical triad of endocrinopathies, café au lait pigmentation, and polyostotic fibrous dysplasia of bone. We hypothesized that children diagnosed with fibrous dysplasia are not routinely being evaluated for coexisting endocrine dysfunction or MAS. Our objective was to prospectively screen subjects with fibrous dysplasia for endocrine disease and G(s)alpha gene (GNAS1 )-activating mutations. STUDY DESIGN: Nine subjects who presented with fibrous dysplasia and were followed in orthopedic clinics were evaluated for other manifestations of MAS. Genomic DNA was isolated from blood, and mutation analysis of GNAS1 was performed. RESULTS: On physical examination, 5 of 9 subjects were found to have café au lait pigmentation. Three of 9 subjects had TSH levels below the normal range. One of these subjects was found to have hyperthyroidism and was treated by total thyroidectomy. GNAS1 mutations were identified in 5 of 9 subjects with either monostotic or polyostotic fibrous dysplasia of bone. CONCLUSIONS: We conclude that a substantial proportion of children being followed for fibrous dysplasia of bone have unrecognized clinical and laboratory features of MAS. These children are at risk for endocrinopathy and should be screened accordingly.     

Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome

Thirteen patients with McCune-Albright syndrome (MAS) and bone fibrous dysplasia (BFD) have been treated for 2-6 years with pamidronate, an aminobisphosphonate which inhibits osteoclastic function. MAS is a rare genetic condition caused by constitutive activating mutations of the Gs protein and manifests with skin dysplasia, bone fibrous dysplasia, and multiple endocrinopathies. Raised serum alkaline phosphatase and urinary hydroxyproline have been reported in these patients, indicating bone metabolic hyperactivity. Encouraging therapeutic results have been achieved with pamidronate, mainly in adults. In our study, treatment reduced bone pain, fracture rate and metabolic indices of bone turnover, in particular significantly decreased bone alkaline phosphatase and cross-links (Wilcoxon test; p <0.06), and increased bone mineral density (DEXA). Signs of healing, such as thickening of the cortical bone, were found in some patients. Three patterns of MRI were found: homogeneous hypointense fibrous tissue, 'dotted' hypointense fibrous tissue, and hyperintense cystic images. Pamidronate treatment can be considered a favorable therapeutic option for patients with MAS.     

Stickler's syndrome or hereditary progressive arthro-ophthalmopathy

A case of Stickler's syndrome is reported. This syndrome associates eye defects, craniofacial and musculo-skeletal abnormalities, sensori-neural hearing loss and mitral-valve prolapse. It is an autosomal dominant disorder probably resulting from a connective tissue dysplasia. There is a major risk for the occurrence of serious ocular problems (blindness), and ophthalmologic follow-up has to be performed on affected persons and relatives in order to improve the long term prognosis.     

McCune-Albright syndrome associated with pituitary microadenoma: patient report

McCune-Albright syndrome (MAS) is a rare disorder characterized by the classic triad of precocious puberty, polyostotic fibrous dysplasia and café-au-lait spots. Additional endocrine abnormalities may also be present, including hyperthyroidism, growth hormone excess and hyperprolactinemia. The most commonly encountered endocrine dysfunction is gonadal hyperfunction. Gonadotropin-independent precocious puberty is typically the initial manifestation of MAS in girls. Ovarian cysts may be detected on pelvic ultrasound. Our patient was also found to have pituitary microadenoma, evidenced by dynamic magnetic resonance imaging.     

Visual manifestations of craniofrontonasal dysplasia

In this sample of craniofrontonasal dysplasia, a 44.4% prevalence of visual impairment was observed, with more than half being due to potentially correctable causes of visual loss, including amblyopia and anisometropia. High prevalences of strabismus (88.9%) and V-pattern (55.5%) in craniofrontonasal dysplasia were also demonstrated. All three patients who underwent strabismus surgery showed improvement in ocular alignment postoperatively. This group needs regular eye examinations to assess for visual impairment and provide timely intervention for modifiable causes of visual loss.     

McCune-Albright syndrome: growth hormone and prolactin hypersecretion

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.     

The role of stem cells in fibrous dysplasia of bone and the Mccune-Albright syndrome

Stem cells have become a major area of interest in the treatment of human disease, but more recently, stem cells have come to be appreciated as the cause of disease. Fibrous dysplasia of bone and the McCune-Albright Syndrome evolve from activating missense mutations in Gsalpha in pluripotent embryonic stem cells. The legacy of these mutations remains in a population of mutated multipotent post-natal skeletal stem cells ("mesenchymal" stem cells), which direct the formation of abnormal bone and a fibrotic marrow in fibrous dysplasia. Future therapeutic approaches for the treatment of fibrous dysplasia, the most significant component of the McCune-Albright Syndrome, will depend on a greater understanding of post-natal skeletal stem cell biology and how skeletal stem cells can be manipulated for efficient bone regeneration.