Diagnosis Of McCune-Albright Syndrome Research Articles

THU200 Three Cases Of Prepubertal Vaginal Bleeding

Abstract Disclosure: H. Doi: None. M. Igarashi: None. T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. Introduction: Children with prepubertal vaginal bleeding (PVB) are usually referred to pediatric endocrinologists, because precocious puberty is one of the important causes of PVB. However, the diagnosis remains challenging due to a wide variety of causative diseases beyond endocrinological disorders. We present three illustrative cases of children with PVB in our institution. Case presentations: Case 1. A 2-year-old girl had suppressed serum LH and FSH levels and elevated estradiol level. She had café-au-lait spots with jagged “coast of Maine” borders on her left chest and back. Her bone X ray showed multiple fibrous dysplasia. The diagnosis of McCune-Albright syndrome was made by a triad of skin, bone and hyperfunctioning endocrinopathy. Case 2. A 5-year-old girl had low serum LH, FSH, and estradiol levels. Her pelvic MRI showed a mass in her vagina and contrast enhancement of the vaginal membrane. Although some malignant tumor had been suspected, vaginal observation using cystoscopy revealed a foreign body of a sponge that seemed to be part of a toy. Her vaginal bleeding disappeared after removal. Our multidisciplinary team concluded that this case was not child abuse. Case 3. A 4-year-old girl had been misdiagnosed as central precocious puberty due to slightly elevated gonadotropin levels. She was referred to our hospital because gonadal suppression therapy with leuprorelin didn’t stop her PVB. Although the observation of her urethra, bladder, vagina, and uterus using cystoscopy revealed no abnormal findings, a small fistula on the membrane of her vaginal opening was noted. Finally, the diagnosis of von Willebrand’s disease type I was made by low level of von Willebrand factor. We speculated that her repeated bleeding was triggered by minor trauma with the background of bleeding tendency. When severe bleeding occurs or is expected to occur, factor VIII containing von Willebrand factor should be administered. Discussion: There are various etiologies of PVB. Detailed history taking and physical examination are quite important, but might be difficult for young pediatric patients. Neoplasms and sexual abuse must be ruled out. In case of suspicion of abuse, the patient’s safety should be guaranteed. Inspection using cystoscopy under general anesthesia is a useful option in recurrent PVB cases. It is critical to make the correct diagnosis because the treatments can be totally different. Conclusion: In PVB cases we need to perform detailed assessments including careful history taking, physical examination and necessary testing considering a broad range of possible diseases. Presentation: Thursday, June 15, 2023

Mccune Albright Syndrome/Craniofacial Fibrous Dysplasia and Postcraniectomy Syndrome: Case Report and Literature Review

Introduction: McCune Albright syndrome (MAS) is a rare pathology caused by a genetic mutation of the GNAS1 gene that causes fibrous dysplasia (FD) among other endocrinological and metabolic manifestations (1). Here is presented a case report, in which craniofacial dysplasia (CFFD) produces functional alteration, its treatment, and the management of underlying complications. Case report: A 10-year-old female patient who presented with CFD with progressive involvement of the orbital cavity, compression of the optic nerve and right oculomotor cranial nerves, associated with precocious puberty and the appearance of ‘’café-au-lait’’ spots on the skin and finally, the diagnosis of MAS is made. Right front-parieto-temporal craniectomy and intracanalicular decompression of the optic nerve was performed getting partial improvement of functional alteration. Subsequently, cranioplasty is performed to manage postcraniectomy/trephined syndrome. Discussion: MAS is a genetic postzygotic disease that occurs in early stages of embryonic development, which explains its mosaicism. Among its manifestation is FD, which is explained by the hyperfunctioning nature of the mutation. In the case of DCF, continuous surveillance is required by a multidisciplinary team that includes a neurosurgeon, whose intervention is reserved for cases in which functional alterations occur, following the recommendations given by medical literature regarding the approach and type of surgery. Decompressive craniectomy can be associated with complications such as postcraniectomy/trephined syndrome, which shows improvement or resolution with cranioplasty. Conclusion: The diagnosis of MAS is clinical, and its mosaicism is explained by its early presentation in embryonic development. In the case of FCD with functional compromise, neurosurgical intervention is required, seeking the recovery and preservation of the compromised cranial nerves, avoiding prophylactic decompressions. In case of complications such as postcraniectomy/trephination syndrome, timely cranioplasty should be performed as it turns out to be highly effective as a treatment, however, the need for studies aimed at its characterization and diagnosis arises.

Detection of Gene Mutation for Patients with McCune- Albright Syndrome and Diagnosis Experience: A Report of Two Cases and Literature Review

Background: McCune-Albright Syndrome (MAS) is a rare disease characterized by a broad spectrum of syndromes, including hyperfunctioning endocrinopathies, café-au-lait leisions, and multiple bone fibrous dysplasias. The diagnosis of MAS is usually based on clinical symptoms. However, most of MAS patients may not display typical symptoms, which make the early diagnosis and treatment of MAS difficult. Cases: Patient 1, a 7-year and 4-month-old girl, developed vaginal bleeding with no apparent cause. A Café-au-lait macule patch could be seen on the right trunk. E2 was 914pmol/L. FSH <0.1IU/L, Luteinizing Hormone (LH) <0.1IU/L. Performing ultrasound, there was a cystic mass in the left accessory area with ovarian echo. There were bone abnormalities in the long bones of the extremities. Patient 2, a girl aged 4 years and 9 months, has abnormal enlarged breasts with no obvious cause. There was a cystic mass in the left accessory area with ovarian echo No apparent Café-au-lait macule hyperpigmented skin macule was seen. E2 is 800pg/ml, FSH <0.1IU/L, LH is 0.2IU/L. GNAS mutation were both positive in the cyst tissue but was negative in the peripheral blood. Conclusion: Gene sequencing is the confirmable proof in diagnosis of MAS. Negative GNAS gene mutation results in the peripheral blood and skin cannot completely rule out the possibility of MAS. Biopsy of the lesion tissues, such as ovarian tissue, may present more efficient results. New detection techniques have higher sensitivity and make molecular diagnosis more accurate.

Craniofacial Fibrous Dysplasia Involvements of Mccune-Albright Syndrome: A Review with an Additional Case.

McCune-Albright Syndrome (MAS) is a genetic disorder with a triad of endocrine diseases, café-au-lait macules and fibrous dysplasias. Craniofacial fibrous dysplasia is a term that is used to describe the fibrous dysplasia, which was localized at the craniofacial skeleton and is common in MAS patients. The objective of this review is to determine the involvement frequency of cranial and facial bones in patients with MAS and CFD. Articles in PubMed was searched with the following details "(mccune[Title/Abstract] OR albright[Title/Abstract]) OR ("craniofacial fibrous dysplasia"[MeSH Terms] OR ("craniofacial"[ All Fields] AND "fibrous"[All Fields] AND "dysplasia"[All Fields]) OR "craniofacial fibrous dysplasia"[All Fields])". The articles in which the authors did not state the involved bones or did not add any radiographic images were excluded from the study. 26 cases in 25 articles met the inclusion criteria. Among the 26 cases and our case, sphenoid and frontal bones were involved in 17 cases, parietal and occipital bones were involved in 15 cases, mandible and ethmoid bone were involved in 14 cases, maxilla-zygoma-temporal and palate was involved in 13, 11, 6 and 3 cases, respectively. Palate was involved in cases where maxilla was also involved. Our case was the only case that was evaluated with CBCT. Routine follow-ups are important since new CFDs can occur in different cranial or facial bones. 2D imaging techniques may not be able to demonstrate early CFDs; thus, an advanced imaging technique should be used after MAS diagnosis.

A case of McCune Albright syndrome in the context of an ovarian mass and late development of café-au-lait macules

McCune-Albright syndrome (MAS) is a genetic disorder characterized by polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots. In this case, a patient presented with precocious puberty in the setting of an ovarian mass and late development of café-au-lait macules, confounding the final diagnosis of MAS. A 3-year-old girl presented with vaginal bleeding. She had a previous episode of vaginal bleeding, breast budding, and a right ovarian cyst at 5 months of age. Work-up at that time showed no abnormal findings, though past medical history was notable for two fractures. Physical exam was significant for increased height (89th percentile), increased weight (99th percentile), bilaterally elevated breast mounds with palpable breast tissue and darkened areolae (Tanner stage 3), and residual blood in the vaginal introitus. Notable labs included low FSH and high ultrasensitive estradiol. Pelvic MRI showed a right ovarian cyst, which, in the context of precocious puberty, raised the suspicion for a juvenile granulosa cell tumor. Follow-up pelvic MRI demonstrated features that instead suggested an ovarian response to hormonal stimulation. On a subsequent visit several months later, the patient had small café-au-lait macules on the chest and right buttock, which were not present on the initial evaluation. Further workup revealed advanced bone age on an x-ray at 6 years 10 months, and multifocal polyostotic fibrous dysplasia involving bilateral femurs and right tibia. Failure to include MAS in the differential had led to unnecessary oophorectomy. It is crucial to identify MAS as a cause of peripheral precocious puberty to guide proper management.

Natural History and Progression of Craniofacial Fibrous Dysplasia: A Retrospective Evaluation of 114 Patients From Massachusetts General Hospital

The natural history of fibrous dysplasia (FD) is poorly understood. The purpose of this study was to identify differences in demographic, clinical, and radiographic characteristics among patients with craniofacial FD, including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD). We hypothesized that patients with MAS would show higher disease severity, have more complications, and undergo more operations than those with PFD or MFD. A retrospective cohort study of patients with MAS or FD, evaluated at Massachusetts General Hospital from 2000 to 2018, was implemented. Patients of all ages and genders were identified through Massachusetts General Hospital Data Registries using International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes.Those with adequate clinical and radiographic data were included. Predictor variables were diagnosis of MAS, PFD, or MFD; age; and gender. Outcome variables included severity of disease at initial presentation (aggressive, nonaggressive and slow growing, or quiescent), number of operations, and complications: pain, sensory disturbances, pathologic fracture, airway obstruction, osteomyelitis, and dental findings. Data were analyzed with descriptive statistics and assessed for significance using χ2 tests and analysis of variance (P<.05). A total of 229 patients were identified: 114 had craniofacial FD, and 70 of these 114 (61.4%) met the inclusion criteria (48 of whom were female patients). The average age at diagnosis was 23.5years; mean length of follow-up, 5.8years. Diagnoses included MAS in 9 patients, PFD in 24, and MFD in 37. Signs and symptoms at initial presentation were pain (n=29), sensory abnormalities (n=13), facial deformity or swelling (n=54), and dental findings (n=25). At presentation, the biological behavior of disease was 77.8% aggressive, 11.1% nonaggressive, and 11.1% quiescent in the MAS group; 41.7%, 41.7%, and 16.7%, respectively, in the PFD group; and 29.7%, 29.7%, and 40.5%, respectively, in the MFD group. Patients with MAS were younger and were more likely to have pain, pathologic fractures, more bones involved, bilateral disease, and visual symptoms than those with PFD or MFD. MAS patients underwent more operations (mean, 4.2±4.18) than those with PFD (mean, 2.6±2.31; P=not significant) or MFD (mean, 1.7±1.28; P=.010). The results of this study indicate that patients with MAS, presumably with the same mutation, are more likely to have aggressive disease, complications, and more operations than those with PFD or MFD.

Pathological Proximal Femoral Fracture in Mc-Cune Albright Syndrome: A Case Report

A 25-year-old female present to us in the emergency department with atraumatic fracture of the proximal femur. She had a cafe-au-lait spot on the face and gave history of precocious puberty. A skeletal survey showed polyostotic fibrous dysplasia.A clinico-radiological diagnosis of McCune-Albright syndrome was made which was further confirmed on biopsy. An extra-medullary fixation was done and at 6 months follow-up, the fracture had united and the patient could walk without support.

A case report of Proteus syndrome (PS)

BackgroundProteus syndrome (PS) is an extremely rare disease characterized by excessive chimeric growth of cells, and progressive and irregular asymmetrical hyperplasia.Case presentationHerein, a PS case with atypical clinical features and syndromes was reported, to improve the understanding of the diagnosis and treatment of the disease. The case was a 3-year-and-11-month-old male child. He was admitted due to a primary diagnosis of McCune-Albright syndrome. After admission, the lesion samples from the milk coffee spots, and nodular thickening skin at hands and feet were subjected to genetic screening. Genetic testing results confirmed the diagnosis of PS.ConclusionsBased on the clinical manifestations, laboratory tests, imaging data, and literature reviewing, the etiology, diagnosis, treatment and prognosis of PS have been analyzed and discussed.

MDP Bone Scintigraphy in Diagnosis of Polyostotic Fibrous Dysplasia- A Case Report on McCuneAlbright Syndrome

&lt;p&gt;&lt;span&gt;McCune-Albright syndrome (MAS) is an extremely rare disorder that classically affects the bones, skin and endocrine system. Classical features are fibrous dysplasia of bone, skin pigmentation and dysfunction of certain endocrine glands. Diagnosis of MAS is usually established on clinical grounds. Different imaging modalities help to confirm the fibrous dysplasia, among those radio iso-tope bone scan is an excellent tool for early diagnosis and evaluation of bony extension.&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;Bangladesh J. Nuclear Med. 19(1): 61-63, January 2016&lt;/span&gt;&lt;/p&gt;

Acromegaly with hypophosphataemia: McCune-Albright syndrome

A 38-year-old man presented with excessive height gain and progressive enlargement of the extremities since childhood. This was compounded by lower limb deformities over the past 5 years. On examination,...

The Use of Real Time PCR Genotyping to Detect Activating GNAS Mutations in McCune-Albright Syndrome

Introduction: The McCune-Albright syndrome (MAS) is a genetic disease clinically characterized by the triad: bone fibrous dysplasia cafe-au-lait skin spots and endocrine hyperfunction, such as precocious puberty. MAS is due to activating mutations of GNAS, the gene encoding Gs alpha and mutations analysis of this gene could increase the definitive diagnosis of MAS and atypical and partial. Objectives: To identify the p.R201H and p. R201C GNAS activating mutations in multiple tissues derived from patients with MAS using real time PCR genotyping. Material and methods: Genomic DNA was isolated from blood from 31 patients (28 females) with typical and atypical forms of MAS. Skin, adrenal gland or bone tissue samples were also available from six different patients. Genotyping based on PCR real time assay using TaqMan probes was performed for identification of p.R201H and p. R201C GNAS mutations. Cloning and sequencing were used as assenting techniques. Results: Using real time PCR genotyping, no mutations in GNAS were identified in blood samples of MAS patients, only in bone sample of a patient with a previously identified p.R201H. Cloning and sequencing from blood of this same patient revealed that 5/150 clones harboring the p. R201H. Conclusion: The real time PCR genotyping proved to be efficient for the molecular diagnosis of MAS in affected patient's tissues. Advantages of this technique are rapidity, accuracy, it is generally easy to perform and could be used routinely. Nevertheless, optimization of GNAS detection mutation is still necessary to considerer this technique to earlier diagnosis of non-classical forms of MAS using peripheral blood.

McCune-Albright syndrome revealed by hyperthyroidism at advanced age

We report a case of a 38-year-old woman admitted to our service for diagnosis of osteolytic lesions. She suffered from back, lumbar and costal pain at the time a hyperthyroidism, related to multinodular goiter, was diagnosed. The pain remained despite the cure of hyperthyroidism. Cutaneous examination revealed café au lait skin spots. Analysis of the phosphocalcic metabolism allowed the diagnosis of phosphate diabetes. X-ray showed lytic lesions involving the ribs with thinning of the cortex and vertebral fractures of the dorsal spine. The computed tomography revealed lytic lesions with a typical “ground glass” appearance involving the spine, ribs, sternum, iliac bones and sacrum. The presence of this clinical triad allowed the diagnosis of McCune-Albright syndrome (MAS). The treatment consisted in vitamin D supplementation, and high doses of both oral phosphate and calcitriol to treat the phosphate diabetes as well as cycles of intravenous pamidronate administration to relieve bone pain. We report an uncommon case of the diagnosis of MAS at an advanced age following hyperthyroidism. We believe that the disease was revealed by an increase in bone turnover due to hyperthyroidism.

McCune-Albright syndrome

McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS.

Oophorectomy in McCune-Albright syndrome: a case of mistaken identity

Objective The objective of the study was to determine the incidence of oophorectomy in girls presenting with precocious puberty and vaginal bleeding who are subsequently diagnosed with McCune-Albright syndrome (MAS). Study Design Medical records of girls diagnosed with MAS between 1988 and 2005 were reviewed. Variables analyzed included presenting features, presence of café au lait macules, presence of fibrous dysplasia, radiographic studies, estradiol levels, tumor markers, surgery, and pathology reports. Results Nine girls with MAS were identified. Average age at initial presentation was 3.2 ± 2.1 years (range, 0.6-7 years). All patients presented with sudden onset of vaginal bleeding. Eight (88%) also had breast development and 2 (22%) had associated pubic hair. Four (44%) girls underwent salpingo-oophorectomy before the diagnosis of MAS was made. Of these, 3 had café au lait macules on initial presentation, and 3 were later diagnosed with fibrous dysplasia. Surgical pathology revealed benign ovarian cysts in all 4 patients. Conclusion Unnecessary oophorectomy is common in girls with MAS who are taken to the operating room for a presumed ovarian tumor. This highlights the need for increased awareness of MAS among pediatricians, pediatric surgeons, and emergency room physicians. Distinguishing features, which can be helpful in differentiating these 2 conditions, are often present.

Clinical Presentation of McCune-Albright Syndrome in Males

The aims of this study were: (a) to survey gender prevalence and clinical findings at diagnosis in a series of patients who manifested at the time of this study the classical triad of McCune-Albright syndrome (MAS); (b) to investigate whether clinical presentation of MAS in boys may be different from that in girls; (c) to confirm whether boys with MAS may show a peculiar picture of testicular microlithiasis (TM) by testicular ultrasonography (US). Twenty-six patients (10 boys) with the classical clinical manifestations of MAS were recruited for the present study from the database of the Italian Multicenter Study Group on MAS. Age at diagnosis of MAS was significantly lower in girls than in boys (p < 0.025). Whilst there was no difference in the prevalence of skin and bone fibrous dysplasia for the two groups, a significantly higher prevalence of peripheral precocious puberty (PPP) was found in girls (chi2 = 6.5, p < 0.025). Moreover, PPP onset was earlier in females than in males (2.8 +/- 2.3 vs. 6.9 +/- 2.7 years, p < 0.005). In one boy, aged 2.9 years, the first clinical manifestation of MAS was monolateral testicular enlargement in the context of a picture of classical PPP. US scanning of the testes, at the time of the present study, showed bilateral hyperechogeneic multiple spots, compatible with diagnosis of TM, in 6/10 boys. (a) MAS is slightly more frequent in females. (b) PPP in MAS is significantly more frequent and earlier in girls. (c) PPP in boys with MAS is generally associated with bilateral testicular enlargement, but monolateral macroorchidism may also be seen. (d) TM may be another marker for MAS in males.

Laparoscopic Management of Ovarian Cystsin Peripheral Precocious Puberty of McCune-Albright Syndrome

Ovarian cysts are common in peripheral precocious puberty in McCune-Albright syndrome (MAS). The clinical course of these cysts is unpredictable due to episodes of hyperestrogenism typical of MAS ovarian hyperfunction. In persistent and recurrent large ovarian cysts with sustained estrogen hypersecretion and relevant clinical disturbances (increased linear growth and bone age maturation, vaginal bleeding and psychological disturbances) treatment is mandatory. Experimental courses of estrogen-blocking drugs may have insufficient or nil therapeutic effects. In these cases and when molecular analysis is required to obtain MAS diagnosis as in isolated peripheral precocious puberty, surgery is the option. Laparoscopy minimizes surgical aggression and facilitates obtaining tissue samples for molecular analysis, and sometimes relieves hyperestrogenism with the excision of hyperactive ovarian areas. It can be conducted with trans-umbilical laparoscopic ovarian cystectomy (TULOC) before 3 years of age and with traditional techniques afterwards.

Recurrent Ovarian Cysts in Childhood: Diagnosis of McCune-Albright Syndrome by Bone Scan

During the past decade, it has become clear that precocious puberty is a complex disorder with multiple pathophysiologic causes. Although gonadotropin-releasing hormone (GnRH)-dependent mechanisms account for the vast majority of precocious puberty in girls, GnRH-independent processes play an important role in a minority of patients. The recent availability of specific therapies for both GnRH-dependent and GnRH-independent precocious puberty has made it increasingly important for pediatricians to distinguish between these two subsets.1,2 Although most patients with precocious puberty neatly fall into one or the other subset, a significant minority of patients may present a diagnostic challenge even after an extensive evaluation is undertaken.

McCune‐Albright Syndrome with Multiple Bilateral Cafe au Lait Spots

A 7-week-old infant developed hyperpigmented lesions at 5 days of age that gradually progressed to sharply demarcated, medium-brown macules of unusual configuration involving the neck, trunk, buttocks, upper arms, and right upper thigh. A biopsy specimen of a representative lesion showed changes of epidermal melanosis consistent with café au lait spot. At age 15 months the patient developed a limp. Roentgenographic evaluation showed widespread, bilateral changes of fibrous dysplasia, most severe in the right pelvis, femur, and tibia. At the present time he has no evidence of precocious puberty or other endocrinopathies. Despite the absence of endocrine abnormalities, these findings are consistent with a diagnosis of McCune-Albright syndrome with extensive bony and cutaneous lesions.