OBJECTIVE: To explore the genetic basis for three Chinese patients with McCune-Albright syndrome (MAS). METHODS: Three children who had respectively presented at Shandong Provincial Hospital in April 2019 and Peking Union Medical College Hospital in August 2020 and May 2021 were selected as the research subjects. Peripheral blood samples of the probands and their family members were taken for the extraction of genomic DNA. Potential variants were screened by whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing of the patients and their family members. RESULTS: The proband from family 1 was found to harbor a heterozygous c.601C>T (p.R201C) missense variant in exon 8 of the GNAS gene, whilst the probands from families 2 and 3 were both found to harbor a heterozygous c.602G>A (p.R201H) missense variant in exon 8 of the GNAS gene. Both variants were known to be pathogenic, and all probands were found to be mosaics for the corresponding variants but with various degrees. CONSLUSION WES can effectively diagnose MAS and other somatic genetic disorders. In this study, the combined WES and Sanger sequencing have verified the degree of mosaicisms of pathogenic variants in the three MAS patients, albeit no apparent correlation was found between the degree of mosaicisms and the phenotype of patients. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the affected families.
Humans ; Mutation ; Fibrous Dysplasia, Polyostotic/genetics* ; East Asian People ; Exons ; Phenotype ; Pedigree

Humans ; Fibrous Dysplasia, Polyostotic/complications* ; Hemangioma

Peripheral precocious puberty(PPP),also known as puberty independent from hypothalamic-pituitary axis activation,is stimulated by hormones from other sources, with only partial sexual characteristics development but without mature sexual function. The secondary sexual characteristics development occurs before 7.5 years of age in girls and before 9 years of age in boys. Clinical manifestations are diverse, and PPP has varied etiology including congenital adrenal hyperplasia, McCune-Albright syndrome, ovarian cyst, adrenal tumor, ovarian tumor, testicular tumor, human chorionic gonadotropin producing tumor, familial male precocious puberty, aromatase excess syndrome, and environmental estrogen. Early identification of etiology, accurate differential diagnosis and prenatal gene screening play a significant role in the prevention, diagnosis and treatment of the disease.
Female ; Humans ; Male ; Child ; Puberty, Precocious/therapy* ; Fibrous Dysplasia, Polyostotic/complications* ; Aromatase

OBJECTIVE: To compare the clinicopathologic features and prognosis of the different types of fibrous dysplasia (FD) of cranio-maxillofacial region, so as to provide a new reference for clinicians to treat these patients and make prognostic judgement. METHODS: Clinical records, radiographic data and pathological information of 105 patients diagnosed with FD or McCune-Albright syndrome (MAS) at the Department of Oral Pathology, Peking University Hospital of Stomatology from January 2013 to December 2020 were collected. The patients were divided into 4 groups: monostotic FDs, polyostotic FDs, MAS and a specific type called craniofacial fibrous dysplasia (CFD) limited in the craniofacial region. The clinicopathological characteristics, treatment and follow-up data of each type were analyzed. RESULTS: Of all the 105 patients, 46 were males and 59 were females, with a male-to-female ratio of 1 ∶1.3. The onset age ranged from 0 to 56 years and the median age was 12 years. On the basis of different involvement conditions, 4 types were divided. The most common type was monostotic FDs (43 cases, 40.95%), including maxilla (29 cases), mandibular (12 cases) and zygoma (2 cases). 32 cases (30.48%) were diagnosed with polyostotic FDs, 7 cases (6.67%) were MAS, and 23 cases (21.90%) were CFDs confirmed by computed tomography (CT) analysis. CFD was clearly distinct from other types of FD, such as the patient gender and the serum alkaline phosphatase level in peripheral blood before operative surgery. The pathologic findings of various types FD were quite similar, whilst the predominant fibrous tissue hyperplasia could be observed in polyostotic FDs and MAS types. CONCLUSION The clinicopathologic features of FD in the cranio-maxillofacial region are different from the FD lesions in other parts of the body. The clinicopathological features of CFD are significantly different from those of monostotic and polyostotic FDs in the cranio-maxillofacial region. Therefore, the clinicians should pay attention to distinguish CFD in clinic, imaging and pathology aspects, so as to further clarify its features in clinic management and prognosis.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Fibrous Dysplasia, Polyostotic ; Humans ; Infant ; Infant, Newborn ; Male ; Mandible ; Middle Aged ; Prognosis ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVE: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. METHODS: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m ·d for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. RESULTS: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 ( < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment ( < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed. CONCLUSIONS Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.
Aromatase Inhibitors ; Child ; China ; Female ; Fibrous Dysplasia, Polyostotic ; Humans ; Letrozole ; Puberty, Precocious

Fibrous dysplasia (FD) is a non-malignant bone tumor that typically behaves as a slow and indolent growing mass lesion. We report the case of a female patient presenting with headache and facial deformity and later diagnosed with polyostotic fibrous dysplasia (PFD). A 29-year-old woman visited Mealhada Primary Health Care Unit complaining of headache, nasal congestion, and hyposmia for several weeks. She also presented with facial deformity and painful swelling of the upper left orbit. X-ray imaging revealed a suspicious opacity in the left frontal sinus and a right shift of the nasal septum. Computed tomography and bone scintigraphy later confirmed a tumor involving the ethmoid and frontal bone. The patient was referred to the neurosurgery and otorhinolaryngology departments of a central hospital and the suspected diagnosis of PFD was confirmed. A watchful waiting approach with regular imaging screenings was proposed and accepted by the patient, who is now free of symptoms and more acceptant of the benign condition of her tumor. With this case, we aim to make family physicians more aware of this rare but relevant condition that can be difficult to diagnose. FD is a rare but benign tumor that occurs mainly in adolescents and young adults. Symptoms depend on the location and type of the tumor and include facial deformity, vision changes, nasal congestion, and headache. No clear guidelines exist for its treatment, and options include monitoring the progression of the tumor, in addition to medical or surgical approaches.
Adolescent ; Adult ; Bone Neoplasms ; Congenital Abnormalities ; Diagnosis ; Estrogens, Conjugated (USP) ; Female ; Fibrous Dysplasia of Bone ; Fibrous Dysplasia, Polyostotic* ; Frontal Bone ; Frontal Sinus ; Headache ; Humans ; Mass Screening ; Nasal Septum ; Neurosurgery ; Orbit ; Otolaryngology ; Physicians, Family ; Primary Health Care* ; Radionuclide Imaging ; Watchful Waiting ; Young Adult

PURPOSE: This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). METHODS: The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. RESULTS: The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. CONCLUSION: The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.
Adrenal Hyperplasia, Congenital ; Androgens ; Aromatase Inhibitors ; Child* ; Chorionic Gonadotropin ; Dehydroepiandrosterone Sulfate ; Diagnosis ; Estradiol ; Female ; Fibrous Dysplasia, Polyostotic ; Follow-Up Studies ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Humans ; Luteinizing Hormone ; Male ; Ovarian Cysts ; Prognosis ; Puberty, Precocious* ; Retrospective Studies ; Treatment Outcome ; Uterine Hemorrhage

PURPOSE: This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). METHODS: The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. RESULTS: The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 µg/dL); and human chorionic gonadotropin (hCG)-producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. CONCLUSION: The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.
Adrenal Hyperplasia, Congenital ; Androgens ; Aromatase Inhibitors ; Child* ; Chorionic Gonadotropin ; Dehydroepiandrosterone Sulfate ; Diagnosis ; Estradiol ; Female ; Fibrous Dysplasia, Polyostotic ; Follow-Up Studies ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone ; Humans ; Luteinizing Hormone ; Male ; Ovarian Cysts ; Prognosis ; Puberty, Precocious* ; Retrospective Studies ; Treatment Outcome ; Uterine Hemorrhage

Fibrous dysplasia of the spine is very rarely observed. We reported a case of a 57-year-old woman, who presented with neck and bilateral shoulder pain with histologically confirmed fibrous dysplasia, involving the first and second thoracic vertebrae. Clinical and radiological findings were not specific for fibrous dysplasia. The histological biopsy was required for a confirmed diagnosis. Endocrine and metabolic evaluations are required to rule out diseases such as hyperthyroidism, Cushing syndrome and osteomalacia. Fibrous dyplasia can be managed by appropriate medical and surgical treatments based on the patient's neurological status and symptoms. Our patient was given intravenous pamidronate 60mg/day for 3 days. After 9 months, her initial symptoms were improved, but computed tomography scan of the thoracic spine showed no change of the lesions.
Biopsy ; Cushing Syndrome ; Diagnosis ; Female ; Fibrous Dysplasia of Bone ; Fibrous Dysplasia, Polyostotic* ; Follow-Up Studies* ; Humans ; Hyperthyroidism ; Middle Aged ; Neck ; Osteomalacia ; Shoulder Pain ; Spine* ; Thoracic Vertebrae

OBJECTIVETo investigate the quantitative analysis based on three-dimensional computed tomography (3D-CT) in contouring surgery of complex craniofacial fibrous dysplasia (FD).

METHODS14 patients with craniofacial FD underwent 3D-CT scan. Axial images of patients with craniofacial FD were reconstructed into 3D model by using Mimics 10.0. Anatomical landmarks were located and the coordinate of the landmarks obtained. The differences between the right landmarks and the left were calculated and analyzed. Quantitative contouring surgery was performed based on the quantitative analysis result.

RESULTSWith the detail data from the 3D-CT analysis, the surgery of contouring was more safe and accurate with less operation time, less bleeding and good results.

CONCLUSIONSThe method of 3D CT quantitative analysis can provide precise information in the diagnosis and treatment planning of craniofacial deformity. Based on the result of 3D-CT quantitative analysis, the operations can be performed more accurately and safely with good symmetric consequence.

Aged ; Craniofacial Abnormalities ; diagnostic imaging ; Facial Bones ; abnormalities ; diagnostic imaging ; Fibrous Dysplasia, Polyostotic ; diagnostic imaging ; Humans ; Imaging, Three-Dimensional ; methods ; Tomography, X-Ray Computed ; methods