U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Fibrous Dysplasia / McCune-Albright Syndrome

Synonym: FD/MAS

, MD, , MD, , PhD, and , MD.

Author Information and Affiliations

Initial Posting: ; Last Revision: June 27, 2019.

Estimated reading time: 38 minutes


Clinical characteristics.

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G-protein, Gsα), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gsα signaling is ubiquitous, additional tissues may be affected.

Café au lait skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include:

  • Gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys;
  • Testicular lesions with or without associated gonadotropin-independent precocious puberty;
  • Thyroid lesions with or without non-autoimmune hyperthyroidism;
  • Growth hormone excess;
  • FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and
  • Neonatal hypercortisolism.

The prognosis for individuals with FD/MAS is based on disease location and severity.


In most individuals, the diagnosis of FD/MAS is based on the finding of two or more typical clinical features. In individuals whose only clinical finding is monostotic fibrous dysplasia, identification of a somatic activating pathogenic variant in GNAS by molecular genetic testing is required to establish the diagnosis. Variant detection depends on the level of mosaicism in the tissue and the sensitivity of the technique.


Treatment of manifestations: Management is most effectively accomplished by a multidisciplinary team of specialists.

  • FD. Management focuses on optimizing function and minimizing morbidity related to fractures and deformity (including scoliosis).
  • Precocious puberty. Treatment prevents bone age advancement and compromise of adult height. For girls, the aromatase inhibitor letrozole is used; for boys, treatment options are less well established.
  • Thyroid disease. Methimazole effectively manages hyperthyroidism; however, because hyperthyroidism is persistent, thyroidectomy is common.
  • Growth hormone excess. Medical therapy is the preferred first-line treatment; options include (alone or in combination) octreotide and the growth hormone receptor antagonist pegvisomant.
  • Hypercortisolism. Treatment varies by the presentation of neonatal Cushing syndrome.


FD/MAS. Monitor for the following:

  • Infants: clinical signs of hypercortisolism
  • All children: growth acceleration and other clinical signs of precocious puberty and/or growth hormone excess
  • Children:
    • Age <5 years: thyroid function abnormalities
    • With thyroid abnormalities on ultrasound examination but normal thyroid function: periodic monitoring of thyroid function
  • Males: testicular lesions (physical examination and testicular ultrasound)
  • Individuals on:
    • Pegvisomant: hepatotoxicity
    • Somatostatin analogs: signs and symptoms of gallbladder disease
  • Females: breast cancer (earlier than is recommended for the general population)


  • Periodic radiographs to monitor existing FD and development of new lesions
  • Periodic serum phosphorus (for development of hypophosphatemia) and 25-hydroxyvitamin D levels
  • Craniofacial FD: yearly vision and hearing evaluations; periodic skull CT; routine serum IGF-1 levels through young adulthood
  • Spine FD: close monitoring for progressive scoliosis

Agents/circumstances to avoid: Contact sports and other high-risk activities (when skeletal involvement is significant); prophylactic optic nerve decompression (in individuals with craniofacial FD); surgical removal of ovarian cysts; radiation therapy for treatment of FD; risk factors for malignancy (e.g., radiation exposure).

Genetic counseling.

FD/MAS is not inherited. No parent of a child with FD/MAS has been demonstrated to have any significant, distinctive manifestations of the disorder. The risk to sibs is expected to be the same as in the general population. There are no verified instances of vertical transmission of FD/MAS.


Fibrous dysplasia / McCune-Albright syndrome (FD/MAS) is usually diagnosed on clinical grounds, although formal diagnostic criteria have not been published.

Suggestive Findings

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS) should be suspected in individuals with any of the following skin, skeletal, or endocrine features.

Skin. Individuals may have characteristic café au lait skin macules.

  • Borders are jagged and irregular, often referred to as resembling the "coast of Maine" (in contrast to the smooth-bordered "coast of California" lesions seen in neurofibromatosis type 1).
  • Distribution shows an association with ("respecting") the midline of the body and following the developmental lines of Blaschko, which reflect patterns of embryonic cell migration (see Figure 1).
Figure 1.

Figure 1.

Café au lait skin pigmentation A. Skin lesions in a newborn demonstrating the characteristic association with the midline of the body, and distribution reflecting patterns of embryonic cell migration (developmental lines of Blaschko)

Skeletal. Fibrous dysplasia (FD), a condition in which normal bone and bone marrow are replaced by fibroosseous tissue, results in an increased risk of fractures, deformity, functional impairment, and pain.

  • FD can be classified as monostotic (i.e., involvement of 1 bone) or polyostotic (i.e., involvement of >1 bone).
  • FD can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton (see Figure 2).
  • The initial radiologic evaluation for FD should include a 99Tc-MDP bone scan.
    • Areas of skeletal involvement identified on scintigraphy should be further evaluated with radiographs and head computerized tomography (CT), depending on the location and extent of the disease.
    • See Figure 3 for the suggested evaluations used to diagnose FD.
Figure 2.

Figure 2.

Fibrous dysplasia (FD) A. Proximal femur FD demonstrating the typical ground-glass appearance with a coxa vara ("shepherd's crook") deformity

Figure 3.

Figure 3.

Suggested evaluations to determine if fibrous dysplasia (FD) is present and the extent of disease if FD is present

Endocrine. Findings may include the following:

  • Gonadotropin-independent precocious puberty
  • Testicular lesions including Leydig and/or Sertoli cell hyperplasia with characteristic ultrasonographic features, with or without associated gonadotropin-independent precocious puberty (See Figure 4B.)
  • Thyroid lesions with characteristic ultrasonographic features, with or without non-autoimmune hyperthyroidism (See Figures 4C and 4D.)
  • Growth hormone excess
  • Fibroblast growth factor 23 (FGF23)-mediated phosphate wasting with or without hypophosphatemia
  • Neonatal hypercortisolism
Figure 4.

Figure 4.

Ultrasonography A. Pelvic ultrasound in a girl age seven years, showing a complex unilateral ovarian cyst (defined by cross-hatches). The uterus is prepubertal in size (arrow).

Establishing the Diagnosis

The diagnosis of FD/MAS is established in individuals who have two or more typical clinical features of FD/MAS. In individuals whose only clinical finding is monostotic fibrous dysplasia, identification of a somatic activating GNAS pathogenic variant is required to confirm the diagnosis (see Table 1).

Molecular genetic testing approaches include targeted analysis of codons p.Arg201 and p.Gln227. Testing a sample of the lesional tissue, if possible, has the highest clinical sensitivity in PCR-sequencing-based diagnostic methods:

  • ~80% in lesional tissue
  • ~20%-30% in peripheral blood lymphocytes

Note: (1) Variant detection depends on the level of mosaicism in the tissue and the sensitivity of the technique. Detection frequency of a variant at p.Arg201 using standard PCR was highest in endocrine organs and lowest in affected skin specimens [Lumbroso et al 2004]. The ability to detect mosaicism affects the detection rate of the assay (see Table 1 and Table 4). (2) Targeted analysis may be performed by sequencing of GNAS exons 8 and 9. GNAS variants other than those previously reported to be associated with FD/MAS would likely be interpreted as variants of unknown significance. (3) Gsα is expressed in nearly all tissues from both maternal and paternal GNAS alleles. However, GNAS is a complex locus where alternative transcripts and additional phenotypes may result from GNAS imprinting (see Genetically Related Disorders and Molecular Genetics).

Table 1.

Molecular Genetic Testing Used in Fibrous Dysplasia / McCune-Albright Syndrome

Gene 1MethodVariants DetectedProportion of Probands with a Pathogenic Variant 2 Detectable by Method
GNAS Targeted analysis of lesion biopsy of exons 8 and 9 3, 4p.Arg201His, p.Arg201Cys 5, 68%-90% 7
75%-100% 8
p.Gln227Leu 65% 5

See Table A. Genes and Databases for chromosome locus and protein.


See Molecular Genetics for information on allelic variants detected in this gene.


Targeted analysis may be performed by sequence analysis. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Testing tissue from a lesion biopsy has a higher clinical yield than testing a blood sample. The detection rate for a blood sample is ~20%-30% [Lumbroso et al 2004, Kalfa et al 2006].


Somatic GNAS missense variants in individuals with FD/MAS are known to occur at only one of two amino acid residues: p.Arg201 (>95% of pathogenic variants) [Lumbroso et al 2004] or p.Gln227 (<5%) [Idowu et al 2007].


Rarely, other amino acid substitutions at p.Arg201 and at p.Gln227 have been detected (see Molecular Genetics).


Variant detection depends on the level of mosaicism in the tissue and the sensitivity of the technique. Variant detected at p.Arg201 using standard PCR was highest in endocrine organs and lowest in affected skin specimens [Lumbroso et al 2004].


When modified primers (peptide nucleic acid) [Bianco et al 2000] and next-generation sequencing [Narumi et al 2013] technologies are combined [Narumi et al 2013], a p.Arg201 variant can be detected in virtually all affected tissues and in leukocytes of up to 75% of individuals.

Clinical Characteristics

Clinical Description

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS) results from mosaic somatic activating pathogenic variants in GNAS, which encodes the cAMP pathway-associated G-protein, Gsα. Affected tissues can include those derived from ectoderm, mesoderm, and endoderm, and commonly include skin, skeleton, and certain endocrine organs. However, because Gsα signaling is present in virtually every tissue, additional sites may be affected.

The phenotypic spectrum of FD/MAS ranges from asymptomatic incidental findings to neonatal lethality. There is a high degree of variability between individuals, both in the number of affected tissues and the degree to which they are affected. Disease manifestations depend on the time during embryogenesis that the somatic pathogenic variant occurred, the tissue involved, and the role of Gsα in the affected tissue. Pathogenic variants occurring early in development lead to widespread disease, while those occurring later in development lead to limited disease.

Pigmented macules. Café au lait skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. There is no correlation between the size of the skin lesions and the extent of disease, nor between the distribution of skin lesions and the location of fibrous dysplasia.

Fibrous dysplasia of bone. As with skin, fibrous dysplasia demonstrates a mosaic pattern: it can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton. The bones most commonly involved are the skull base and proximal femurs [Kelly et al 2008]. While there is generally a central-to-peripheral gradient, any combination of involved bones is possible.

Fibrous dysplasia can manifest along a wide spectrum: from an isolated, asymptomatic monostotic lesion discovered incidentally to severe, disabling polyostotic disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.

Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age ten years, with few new and almost no clinically significant bone lesions appearing after age 15 years [Hart et al 2007]. In adulthood, fibrous dysplasia lesions typically become less active, likely related to apoptosis of pathogenic variant-bearing cells [Kuznetsov et al 2008].

The clinical presentation and course of fibrous dysplasia (FD) depends on the location and extent of the affected skeleton:

  • Appendicular skeleton
    • Children with fibrous dysplasia in the appendicular skeleton typically present with a limp, pain, and/or pathologic fractures.
    • Recurrent fractures and progressive deformity may lead to difficulties with ambulation and loss of mobility.
  • Craniofacial region
    • FD may present as a painless "lump" or facial asymmetry.
    • Expansion of craniofacial lesions may lead to progressive facial deformity (see Figure 2B), and in rare cases (usually in association with growth hormone excess) loss of vision and/or hearing due to compromise of the optic nerves and/or external auditory canals [Cutler et al 2006, Boyce et al 2018].
  • Vertebrae
    • FD involving the vertebrae is common, and may lead to scoliosis, which in rare instances may be severe, progressive, and even lethal [Leet et al 2004b].
    • Untreated, progressive scoliosis is one of the few features of FD that can lead to early morbidity.

Bone pain is a common complication of fibrous dysplasia. Although bone pain may present at any age, it is common for bone pain to be absent in childhood, occur in adolescence, and progress into adulthood [Kelly et al 2008].

Aneurysmal bone cysts are rapidly expanding fluid-filled lesions that form within preexisting areas of FD. Such lesions are best detected by MRI. Affected individuals experience acute onset of severe pain, rapidly expanding localized deformity, and rarely – when cysts compress the optic nerve – rapid loss of vision. Aneurysmal bone cysts thus carry a high risk of morbidity (see Management).

Malignant transformation of FD lesions is a rare complication. Many instances of malignant transformation were reported in association with previous radiation treatment [Ruggieri et al 1994]. Growth hormone excess may be a predisposing factor [Salenave et al 2014].

Radiographic appearance of fibrous dysplasia varies according to location:

  • Radiographs of the appendicular skeleton show expansive lesions with endosteal scalloping, thinning of the cortex, and a "ground glass" appearance (Figure 2A).
  • Fibrous dysplasia in the craniofacial skeleton is typically expansile and appears sclerotic on x-ray, but demonstrates a typical "ground glass" appearance on computed tomography (CT) (Figure 2C).
  • With aging, fibrous dysplasia lesions in the appendicular skeleton tend to become sclerotic on radiographs and craniofacial fibrous dysplasia lesions develop a "cystic" appearance (Figure 2D).

Endocrinopathies can include any of the following:

  • Precocious puberty. Precocious puberty is common in girls with FD/MAS (~85%), and is often the presenting feature. Recurrent ovarian cysts (Figure 4A) lead to intermittent estrogen production resulting in breast development, growth acceleration, and vaginal bleeding; during the intervals between cyst formation, breast tissue typically regresses and estrogen levels fall to prepubertal levels. Ovarian cysts typically continue into adulthood, leading to irregular menses. This has the potential to interrupt ovulatory cycles, which may increase the time to conception in adult women. Ovarian torsion has been seen rarely in girls and women with large and persistent cysts [Clark et al 2000].
    Precocious puberty is less common in boys with FD/MAS (~10%-15%), and is due to autonomous testosterone production [Boyce et al 2012a], which leads to progressive pubertal development including growth acceleration, pubic and axillary hair, acne, and aggressive and/or inappropriately sexual behavior.
    In both girls and boys, prolonged autonomous sex steroid production typically leads to activation of the hypothalamic-pituitary axis and the development of central precocious puberty.
  • Fertility. The effects of autonomous sex steroid production on pituitary-gonadal function and fertility in adults are not well characterized. Women with FD/MAS may have recurrent cysts leading to irregular menses in adulthood [Lala et al 2007]. While many women in the NIH cohort have achieved successful pregnancies, it is possible that interruption of ovulatory cycles could decrease fertility and increase the time to conception [Authors, personal observation].
  • Testicular abnormalities. Testicular abnormalities are seen in the majority of boys and men with MAS (~85%), and typically manifest as unilateral or bilateral macroorchidism [Boyce et al 2012a]. Ultrasound examination demonstrates discrete hyper- and hypoechoic lesions and microlithiasis, corresponding to areas of Leydig and/or Sertoli cell hyperplasia (Figure 4B).
    The potential for malignant transformation of testicular lesions is unknown, but appears to be low [Boyce et al 2012a].
  • Thyroid disease. Thyroid involvement in FD/MAS is common. Approximately half of individuals with FD/MAS have ultrasound findings consistent with thyroid involvement, including mixed cystic and solid lesions interspersed with areas of normal-appearing tissue (Figure 4C and 4D) [Celi et al 2008, Tessaris et al 2012].
    Hyperthyroidism is present in 10% to 30% of individuals with FD/MAS, and results from both increased hormone production and increased conversion of thyroxine (T4) to triiodothyronine (T3) [Celi et al 2008].
    Hyperthyroidism is typically mild to moderate, but may be severe, and if undetected can lead to thyroid storm during anesthetic induction for surgery [Lawless et al 1992].
    Uncontrolled hyperthyroidism may lead to bone age advancement, elevated bone turnover, and fractures.
    Malignant transformation of affected thyroid tissue has rarely been reported [Collins et al 2003].
  • Growth hormone excess. Approximately 15%-20% of individuals with FD/MAS harbor GNAS pathogenic variants in the anterior pituitary that can lead to autonomous growth hormone production; approximately 80% of affected individuals with autonomous growth hormone production also have hyperprolactinemia [Salenave et al 2014].
    Affected individuals typically present with linear growth acceleration, and may develop features of acromegaly. Clinically, growth hormone excess must be distinguished from precocious puberty and hyperthyroidism, which also present with growth acceleration.
    Untreated growth hormone excess is associated with expansion of craniofacial fibrous dysplasia, leading to macrocephaly and increased risk of vision loss [Boyce et al 2013] (see Figure 2B).
  • FGF23-mediated phosphate wasting. In the majority of individuals with FD, increased production of the phosphaturic hormone FGF23 in FD tissue results in a renal tubulopathy with some degree of phosphate wasting [Collins et al 2001]. However, frank hypophosphatemia in persons with FD is infrequent, in part due to alterations in FGF23 processing that takes place in FD tissue and results in increased cleavage of FGF23 to its inactive fragments [Bhattacharyya et al 2012]. The degree of FGF23 overproduction in FD correlates with disease severity and skeletal burden; thus, frank hypophosphatemia is only seen in individuals with a substantial FD burden [Riminucci et al 2003].
    In contrast to most other features of FD/MAS, hypophosphatemia may wax and wane over the course of a person's lifetime and become more severe during periods of rapid skeletal growth. Hypophosphatemia may resolve as persons with FD become older, likely reflecting the intrinsic changes in FD that occur with age [Kuznetsov et al 2008].
    Affected individuals with frank hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain [Leet et al 2004a].
  • Hypercortisolism. Infants with FD/MAS may rarely present with Cushing syndrome due to excess cortisol production from the fetal adrenal gland [Brown et al 2010, Carney et al 2011]. Clinical symptoms typically develop in the neonatal period, and may be severe, leading to critical illness and death. Spontaneous regression has been reported in approximately half of survivors, presumably related to fetal adrenal involution.


  • Hepatitis and neonatal cholestasis may be pronounced in infants, and generally wane with age to a mild persistent form [Silva et al 2000, Ikawa et al 2016].
  • Hepatic adenomas with an identifiable GNAS activating pathogenic variant have also been reported [Gaujoux et al 2014].
  • Liver failure in adults with FD/MAS has not been described.


  • Gastroesophageal reflux manifests in childhood and may be severe.
  • Upper gastrointestinal polyps have been recently described as a common finding in individuals with FD/MAS [Wood et al 2017].

Pancreas. Approximately 15% of individuals with FD/MAS have pancreatic complications:

  • Pancreatitis
  • Intraductal papillary mucinous neoplasms (IPMN), which may present with variable grades of dysplasia [Gaujoux et al 2014, Wood et al 2017]
    An individual with pancreatic carcinoma derived from an intestinal subtype of IPMN has been described [Parvanescu et al 2014].

Myxomas. Intramuscular myxomas are benign, usually asymptomatic, and often found incidentally.


  • Bone and bone marrow are, to varying degrees, replaced by fibroosseous tissue typically devoid of hematopoietic marrow.
  • There have been reports of bone marrow failure with pancytopenia and extramedullary hematopoiesis requiring splenectomy in individuals with FD/MAS [Mahdi et al 2017, Robinson et al 2018].

Breast cancer. The risk for breast cancer in women with FD/MAS may be increased and it can occur at a younger age compared to the general population. However, pathogenic activating GNAS variants were identified in only half of the breast tumors from women with FD/MAS studied [Majoor et al 2018a].

Health-related quality of life. Several series have shown impaired physical functioning in individuals with FD/MAS, strongly correlated with disease severity. Nevertheless, individuals with this condition show preserved social and emotional functioning. This finding is important for prognosis and parental reassurance [Kelly et al 2005, Majoor et al 2018b].

Genotype-Phenotype Correlations

There are no known genotype-phenotype correlations.

To date, only activating GNAS somatic pathogenic variants at residues p.Arg201 and p.Gln227 have been identified in individuals with FD/MAS.

Disease severity is likely correlated with the degree of mosaicism and the tissues that are affected.


The association of intramuscular myxomas with FD/MAS has been termed "Mazabraud syndrome" [Cox et al 2017].


FD/MAS is rare. While reliable data of prevalence are not available, estimates range between 1:100,000 and 1:1,000,000.

In contrast, fibrous dysplasia (particularly the monostotic form) is not rare, and has been estimated to account for as much as 7% of all benign bone tumors.

FD/MAS affects both sexes and shows no predilection for any particular populations.

Differential Diagnosis

Neurofibromatosis type 1 (NF1) and FD/MAS have several overlapping features, including café au lait macules and skeletal abnormalities. Skin findings in NF1 include six or more café au lait macules, which are generally smooth bordered ("coast of California," as opposed to the irregularly bordered "coast of Maine" lesions seen in FD/MAS). Skeletal features of NF1 include kyphoscoliosis, sphenoid dysplasia, cortical thinning of long bones, and bowing and dysplasia, particularly of the tibia, which may result in pseudarthroses. Distinct features of NF1 include tumors of the nervous system such as neurofibromas and optic gliomas, pigmented iris hamartomas, and axillary freckling. NF1 is caused by heterozygous pathogenic variants in NF1 and is inherited in an autosomal dominant manner.

Cutaneous-skeletal hypophosphatemia syndrome is a mosaic disorder resulting from somatic activating pathogenic variants in HRAS and NRAS [Lim et al 2014]. Affected individuals develop cutaneous lesions (epidermal and large congenital melanocytic nevi) following a mosaic distribution, a mosaic skeletal dysplasia, overproduction of FGF23 resulting in rickets/osteomalacia, and variable other associated anomalies of the eye, brain, and vasculature [Ovejero et al 2016].

Fibroosseous skeletal lesions may have radiologic and/or histologic features similar to fibrous dysplasia. These lesions are typically solitary, are not associated with extraskeletal features, and do not harbor pathogenic variants in GNAS.

  • Giant cell tumors of bone are acquired lesions with histopathologic features similar to fibrous dysplasia, including proliferation of bone marrow stromal cells and the presence of multiple multinucleated giant cells. Giant cell tumors are typically benign, but may result in localized bone destruction and (rarely) metastases.
  • Ossifying fibromas are benign lesions typically affecting the mandible and maxillae and presenting with local expansion of a firm, painless mass. Ossifying fibromas are generally more aggressive than craniofacial fibrous dysplasia lesions, and are treated with surgical excision.
  • Osteofibrous dysplasia lesions typically occur in children younger than age ten years, and most commonly affect the anterior tibia. Affected children present with painless localized swelling and, in rare cases, with fracture or progressive deformity. Radiographs show a well-circumscribed radiolucent lesion with a characteristic sclerotic rim along the intra-cortical surface.
  • Cherubism is characterized by progressive fibroosseous lesions of the mandible and maxilla primarily. It typically presents in early childhood with bilateral symmetric enlargement of the lower face leading to a characteristic "cherubic" appearance in which the eyes appear to gaze upward because of maxillary involvement. Facial deformity progresses during childhood and early puberty, after which it sometimes spontaneously regresses. In most cases, cherubism arises from heterozygous pathogenic variants in SH3BP2. Inheritance is autosomal dominant.


Evaluations Following Initial Diagnosis

After the initial diagnosis, all individuals with fibrous dysplasia / McCune-Albright syndrome (FD/MAS) should be evaluated to determine the extent of disease. The presence of any features of FD/MAS should prompt more detailed clinical evaluation for additional manifestations. The authors recommend the following studies, if they have not already been completed.


  • Total body bone scintigraphy to identify and determine the extent of FD [Collins et al 2005]. The majority of clinically significant skeletal lesions are apparent on bone scan by age five years.
  • Imaging of areas of identified areas of FD with radiographs (axial and appendicular FD) and/or computed tomography (craniofacial FD) to more clearly evaluate the extent and anatomy of the lesions
  • Baseline ophthalmologic, otolaryngologic, and audiologic evaluations in persons with craniofacial FD
  • Skeletal evaluation (See Figure 3.)

Endocrine. A thorough history and physical examination and review of a growth chart (if available) are recommended to evaluate for clinical signs of endocrinopathies:

  • Biochemical screening for hyperthyroidism, growth hormone excess (IGF-1 level), and FGF23-mediated hypophosphatemia (See Figure 3, Figure 6, and Figure 7.)
  • In individuals with clinical signs or a previous history of precocious puberty: biochemical screening, pelvic ultrasound examination (females), and bone age examination (See Figure 5 and Figure 6.)
  • Ultrasound examination of the thyroid gland and testes (in all males) to evaluate for subclinical disease (See Figure 7 and Figure 8.)
  • Testing for hypercortisolism in infants with clinical evidence of Cushing syndrome (hypertension, facial plethora, abdominal obesity, developmental delay, failure to thrive, small for gestational age) (See Figure 9.)

Less common manifestations. Consideration should be given to the less common manifestations cited in Clinical Description with appropriate clinical evaluations and imaging/biochemical studies performed as indicated (see Figure 10 for gastrointestinal evaluation).

Figure 5.

Figure 5.

Recommended evaluations for growth hormone excess in individuals with fibrous dysplasia / McCune-Albright syndrome

Figure 6.

Figure 6.

Recommended evaluations for gonadal abnormalities in females with fibrous dysplasia / McCune-Albright syndrome

Figure 7.

Figure 7.

Recommended evaluations for gonadal abnormalities in males with fibrous dysplasia / McCune-Albright syndrome

Figure 8.

Figure 8.

Recommended evaluations for thyroid abnormalities in individuals with fibrous dysplasia / McCune-Albright syndrome

Figure 9.

Figure 9.

Recommended evaluations for adrenal gland dysfunction in individuals with fibrous dysplasia / McCune-Albright syndrome

Figure 10.

Figure 10.

Recommended evaluations for gastrointestinal issues in individuals with fibrous dysplasia / McCune-Albright syndrome

Treatment of Manifestations

Management is most effectively accomplished through the input of a multidisciplinary team of specialists including an endocrinologist, orthopedic surgeon, physiatrist, ophthalmologist, audiologist, endocrine surgeon, craniofacial surgeon, and clinical geneticist. No consensus management guidelines have been published.

Fibrous Dysplasia

There are no available medical therapies capable of altering the disease course in fibrous dysplasia. Current management is focused on optimizing function and minimizing morbidity related to fractures and deformity. The primary elements of management include the following (see also Figure 11):

  • Orthopedic surgery to repair fractures and to prevent and correct deformities. A surgeon experienced in FD should be consulted, as approaches previously considered standard (e.g., curettage, grafting, external fixation) are frequently ineffective [Stanton et al 2012, Leet et al 2016].
  • Diagnosis and treatment of scoliosis is of particular importance, as it may be rapidly progressive and in rare cases may lead to fatal respiratory compromise. For this reason, all individuals with spinal FD should be monitored closely by an orthopedic surgeon or physiatrist for possible progression. Surgical fusion has been shown to be effective at stabilizing the spine [Leet et al 2004b, Mancini et al 2009].
  • Aneurysmal bone cysts, best detected by MRI, are rapidly expanding fluid-filled lesions that form within preexisting areas of FD. Affected individuals experience acute onset of severe pain, rapidly expanding localized deformity, and rarely – when cysts compress the optic nerve – rapid loss of vision. Aneurysmal bone cysts thus carry a high risk of morbidity and should be evaluated urgently by a surgeon [Lee et al 2012, Manjila et al 2013].
  • Prophylactic optic nerve decompression to reduce the risk of vision loss can in fact increase the risk of vision loss and is thus contraindicated [Lee et al 2002, Cutler et al 2006, Amit et al 2011].
  • Physical therapy to optimize function and attenuate loss of mobility is appropriate. Affected individuals with lower-extremity FD in particular may benefit from therapies to address hip girdle weakness, range of motion, and leg length discrepancies [Paul et al 2014].
  • Intravenous bisphosphonates such as zoledronic acid and pamidronate are usually effective at relieving bone pain. Dosing should be based on symptoms, not on a fixed interval or bone turnover markers. The oral bisphosphonate alendronate has been shown to be ineffective for treatment of bone pain [Boyce et al 2014].
  • Denosumab, a human monoclonal antibody to RANKL, has been used in several cases of FD, with an apparent significant reduction in pain, bone turnover markers, and tumor growth rate. However, it has also been associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation [Boyce et al 2012b, Benhamou et al 2014, Ganda & Seibel 2014]. For this reason, we only recommend the use of denosumab in centers with large experience in the treatment of individuals with FD, ideally in the context of a clinical study.
  • Malignancy should remain a consideration for individuals with acute or rapidly expanding FD lesions, or with atypical radiographic features such as compromise of the bony cortex with an associated soft tissue mass.
Figure 11.

Figure 11.

Recommended management for fibrous dysplasia in individuals with fibrous dysplasia / McCune-Albright syndrome


Precocious puberty. Treatment of precocious puberty is important to prevent bone age advancement and compromise of adult height.

  • Females (see Figure 12). The aromatase inhibitor letrozole is an effective treatment for females [Feuillan et al 2007]. In a recently published study with the longest follow up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity, and predicted adult height [Estrada et al 2016]. Most females also have a decrease in the number of menstrual bleeding episodes while on treatment. Prophylactic surgical intervention for large and persistent ovarian cysts should be undertaken with extreme caution due to the known risk for cyst recurrence and the potential for decreased ovarian reserve in affected women.
  • Males (see Figure 13). Given the rarity of precocious puberty in males, treatment options are less well established. One strategy includes the combination of an androgen receptor blocker (e.g., spironolactone or bicalutamide) and an inhibitor of sex steroid synthesis (e.g., letrozole) [Boyce et al 2012a].

Children of both sexes frequently enter central precocious puberty due to premature sex steroid exposure (see Clinical Description). This typically presents with reappearance of the signs of puberty in a child with previously well-controlled peripheral precocious puberty. Leuprolide therapy in combination with the above medications is an effective therapeutic strategy in most.

Figure 12.

Figure 12.

Recommended management for precocious puberty in girls with fibrous dysplasia / McCune-Albright syndrome

Figure 13.

Figure 13.

Recommended management for gonadal involvement in boys with fibrous dysplasia / McCune-Albright syndrome

Thyroid disease. Methimazole is effective for medical management of hyperthyroidism [Tessaris et al 2012] and is the first line of treatment. Propilthiouracil has been associated with an unacceptable risk of hepatotoxicity in children and therefore is no longer recommended [Ross et al 2016]. Because FD/MAS-associated hyperthyroidism is persistent, most affected individuals ultimately elect for definitive treatment. Thyroidectomy is the preferred definitive treatment in most affected individuals. Total gland resection is generally recommended due to the potential for thyroid tissue regrowth. Selection of an experienced high-volume endocrine surgeon is critical to minimize complications and optimize outcomes. Affected individuals should be monitored post-surgically with yearly ultrasound examination to evaluate for tissue regrowth. See Figure 14.

Radioablation is typically avoided due to potential preferential uptake by tissues bearing a somatic activating GNAS pathogenic variant, which may lead to increased risk of malignancy in the remaining unaffected gland. Additionally, GNAS pathogenic variants are associated with a slight increased risk of malignant transformation in both thyroid and non-thyroidal tissues; the risk is potentially enhanced by radiation exposure.

Figure 14.

Figure 14.

Recommended management for hyperthyroidism in individuals with fibrous dysplasia / McCune-Albright syndrome

Growth hormone (GH) excess. Medical therapy is the preferred first-line treatment. Options include (alone or in combination) somatostatin analogs and the growth hormone receptor antagonist pegvisomant [Boyce et al 2013, Salenave et al 2014] (see Figure 15).

  • In growing children, the therapeutic goal is to maintain the IGF-1 level in the middle of the normal range with an IGF-1 Z-score below 0.
  • In skeletally mature individuals, the goal is to decrease the IGF-1 level to as low as possible.

Medical therapy is typically continued indefinitely, as options for definitive treatment are associated with significant morbidity. Surgery may be technically difficult or precluded due to craniofacial FD. Additionally, given the diffuse pituitary infiltration of GH-producing cells, affected individuals treated surgically require total hypophysectomy with resulting total hypopituitarism [Vortmeyer et al 2012]. Radiation treatment may be effective in refractory cases, but has been associated with fatal malignant transformation of craniofacial FD [Hansen & Moffat 2003, Liu et al 2011].

The hyperprolactinemia that frequently accompanies growth hormone excess is generally responsive to treatment with dopamine agonists, including cabergoline and bromocriptine. This class of drugs could also have an effect on growth hormone excess treatment in those with modest elevations of GH and IGF-1 levels, with or without concomitant hyperprolactinemia [Katznelson et al 2014].

Figure 15.

Figure 15.

Recommended management for growth hormone excess in individuals with fibrous dysplasia / McCune-Albright syndrome

FGF23-mediated phosphate wasting. Treatment of frank hypophosphatemia is the same as in other disorders of FGF23 excess, and includes oral phosphorus and calcitriol. Important therapeutic endpoints include growth velocity and radiographic evidence of epiphyseal healing. Unlike other disorders of FGF23 excess, bone turnover markers in FD/MAS (e.g., alkaline phosphatase) may be constitutively elevated and are not a useful indicator of skeletal response to treatment.

Hypercortisolism. Treatment guidelines for hypercortisolism are difficult to establish given the rarity of neonatal Cushing syndrome. Additionally, affected individuals may be critically ill at presentation, which significantly affects treatment options.

  • Definitive treatment includes surgical removal of the diseased adrenal glands.
  • For medical treatment metyrapone is frequently effective, and is preferred over ketoconazole in children with liver abnormalities.

Spontaneous remission has been clearly documented in some affected individuals [Brown et al 2010]; however, it is not possible to identify prospectively which individuals will undergo remission. The decision to pursue or delay adrenalectomy must be made on an individual basis, taking into account the severity of illness, the ability of medications to control cortisol levels, and the potential effect of continued hypercortisolism on neurodevelopment. See Figure 16.

Figure 16.

Figure 16.

Recommended management for hypercortisolism in individuals with fibrous dysplasia / McCune-Albright syndrome

Pancreatic involvement. Natural history and specific risk of malignancy in FD/MAS-associated intraductal papillary mucinous neoplasms (IPMNs) have not been defined. Until that information becomes available, the authors recommend following guidelines for the evaluation of IPMNs in the general population [Tanaka et al 2012] (see Figure 17).

Figure 17.

Figure 17.

Recommended management for pancreatic involvement in individuals with fibrous dysplasia / McCune-Albright syndrome


Due to the mosaic nature of this condition, the clinical findings in any given affected individual can vary significantly, with some individuals having involvement of only one organ system and others having more widespread involvement. Additionally, some features are age dependent and are either not likely to develop after a certain age or are more likely to affect an older individual as opposed to a child. The following information on surveillance applies to individuals who have already been evaluated for signs and symptoms of the condition and in whom the extent of disease has been assessed; surveillance will need to be tailored to the individual's age and known affected organ systems (see Table 3).

Fibrous Dysplasia

See Figure 3.

  • Individuals with craniofacial FD should have yearly vision and hearing evaluations, and periodic computed tomography of the skull.
  • Individuals with spine FD should be monitored closely for progressive scoliosis.
  • Radiographs should be performed periodically to evaluate new or worsening symptoms and to provide additional information about FD anatomy and bone quality.
  • Phosphorus levels should be checked periodically to monitor for the development of FGF23-mediated hypophosphatemia.
  • 25-hydroxyvitamin D levels should be monitored periodically as part of routine bone health surveillance.


Precocious puberty. All children should be monitored for growth acceleration and other clinical signs of precocious puberty (see Figure 5).

Testicular lesions. It is prudent to monitor all males with regular physical examinations and testicular ultrasound examinations (see Figure 7).

Thyroid. Thyroid function tests (TSH, free T4, and T3) should be performed routinely in all children younger than age five years.

  • Individuals with abnormalities on thyroid ultrasound examination but normal thyroid function tests should continue to have laboratory testing periodically throughout childhood, as the development of frank hyperthyroidism may occur later (see Figure 8).
  • Affected individuals who retain abnormal thyroid tissue following thyroid surgery should be monitored with regular physical examination and periodic thyroid ultrasound examination because of the potential for thyroid tissue regrowth (see Figure 14).

Growth hormone excess. All children should be monitored for growth acceleration.

  • Affected individuals with significant craniofacial FD should have IGF-1 levels monitored routinely through early adulthood.
  • Affected individuals treated medically with somatostatin analogs should be monitored for gallbladder disease, and those treated with pegvisomant should be monitored for hepatotoxicity (see Figure 15).

FGF23-mediated phosphate wasting. Serum phosphorus levels should be monitored routinely in all affected individuals (see Figure 3).

Hypercortisolism. Routine biochemical surveillance is not indicated; however, all infants should be monitored for clinical signs of hypercortisolism.

Affected individuals with a history of Cushing syndrome that has spontaneously resolved should be monitored for late-appearing adrenal insufficiency (see Figure 9).


While a strong association between certain pathogenic variants (i.e., activating GNAS variants at residues p.Arg201 and p.Gln227) and malignancies in FD/MAS is lacking, it is prudent to minimize additional risk factors (e.g., radiation exposure) and encourage vigilance and monitoring.

Given the higher risk of breast cancer in women with FD/MAS, screening should be considered at a younger age than what is recommended for the general population [Majoor et al 2018a].

Table 3.

Surveillance to Consider for Individuals with Fibrous Dysplasia / McCune Albright Syndrome

Musculoskeletal 1 Monitoring for progression of scoliosis & other skeletal findings by orthopedic surgeon or physiatristRoutinely
Computed tomography of the skullEvery 5 yrs or potentially sooner in younger individuals, those w/severe disease, or if vision or hearing deficits develop
Radiographs to evaluate new or worsening symptoms & to provide additional information about FD anatomy & bone qualityPeriodically
Endocrine Puberty (females) Evaluation for growth acceleration & other clinical signs of precocious puberty 2, 3At each visit
Bone age assessmentEvery 6 mos in those w/bone age advancement of ≥2 yrs
Puberty (males) Evaluation for growth acceleration & other clinical signs of precocious puberty 2, 3At each visit
Bone age assessmentEvery 6 mos in those w/bone age advancement of ≥2 yrs
Testicular physical examinationAt each visit
Testicular ultrasoundPeriodically
Thyroid Thyroid function tests (TSH, free T4, T3)Routinely in all children age <5 yrs; every 4-6 mos in children <3 yrs & annually in children >3 yrs throughout childhood if ultrasound abnormalities are present 4
Physical examination of the thyroidPeriodically in those w/retained abnormal thyroid tissue following thyroidectomy 5
Thyroid ultrasoundPeriodically in those w/abnormalities on thyroid ultrasound or who have undergone thyroidectomy 5, 6
Adrenal 7 Clinical signs of hypercortisolism 8In infants at each visit
Signs & symptoms of late-appearing adrenal insufficiency in those w/history of Cushing syndrome that has spontaneously resolved 7At each visit
Serum IGF-1 levelsRoutinely through young adulthood in those w/craniofacial FD
For signs & symptoms of gallbladder disease in those treated w/somatostatin analogsPeriodically
Renal Serum phosphorus & 25-hydroxyvitamin D levels 1, 9Periodically
Eyes Evaluation by ophthalmologist (or neuroophthamologist)Annually in those w/craniofacial FD
ENT Evaluation by audiologistAnnually in those w/craniofacial FD
Gastrointestinal Evidence of hepatotoxicity for those on pegvisomantPeriodically
Oncology Consider initiating breast cancer screening earlier than recommended for general population. 10Periodically

Growth acceleration can also be a sign of growth hormone excess.


Individuals with abnormalities on thyroid ultrasound examination but normal thyroid function tests are at risk for the development of frank hyperthyroidism.


Thyroid tissue can regrow after thyroidectomy.


Routine biochemical surveillance for hypercortisolism is not indicated.


To monitor for the development of FGF23-mediated hypophosphatemia and as part of routine bone health


Agents/Circumstances to Avoid

Contact sports and other high-risk activities should be avoided in those with significant skeletal involvement.

Avoid prophylactic optic nerve decompression (see Treatment of Manifestations).

Surgical removal of ovarian cysts should be performed with caution and only in limited circumstances.

Radiation therapy is not indicated for treatment of FD, and radiation exposure to FD lesions should be limited due to potential risk for malignant transformation [Ruggieri et al 1994].

Radioablation for hyperthyroidism is also typically avoided due to potential preferential uptake by tissues bearing a somatic activating GNAS pathogenic variant, which may lead to increased risk of malignancy in the remaining unaffected gland.

Evaluation of Relatives at Risk

Because FD/MAS is not inherited, relatives are not at increased risk and do not require evaluation.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

While the effects of pregnancy on bone and endocrine disease in women with FD/MAS are not well studied, in the authors' experience most affected women do not experience a worsening of disease during pregnancy.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS) is not inherited.

  • Verified vertical transmission has never been observed.
  • Molecular data indicates that all affected individuals are mosaic for an activating GNAS pathogenic variant that arises sporadically early in embryonic development.

Risk to Family Members

Parents of a proband. No parent of a child with FD/MAS has been demonstrated to have any significant, distinctive manifestations of the disorder, nor would such a finding be expected given the somatic nature of the disease.

Sibs of a proband. Given the somatic mutational mechanism of FD/MAS, the risk for an affected sib would be expected to be the same as in the general population.

Offspring of a proband. There are no verified instances of vertical transmission of FD/MAS, potentially the result of embryonic lethality.

Other family members. The risk to other family members is the same as that in the general population.

Related Genetic Counseling Issues

Considerations in families with an apparent de novo mosaic pathogenic variant. Counseling for recurrence risks in FD/MAS should emphasize that, while no pregnancy is at zero risk, evidence suggests that the risk of recurrence for this disorder is not increased over that of the general population.

Family planning. It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Prenatal Testing

As FD/MAS is the result of postzygotic somatic mutation of GNAS and is not inherited, prenatal testing for FD/MAS is not indicated.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Fibrous Dysplasia / McCune-Albright Syndrome: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Fibrous Dysplasia / McCune-Albright Syndrome (View All in OMIM)


Gene structure. GNAS is a complex locus with an imprinted expression pattern. Multiple gene products, including maternally, paternally, and biallelically expressed transcripts, are derived from the use of four promoters and 5' exons that splice onto a common set of downstream exons [Weinstein et al 2004] (summarized in OMIM 139320). The major GNAS product is the ubiquitously expressed Gsα, which is generated by the most downstream promoter (exon 1). For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. Somatic mosaicism for pathogenic missense variants at p.Arg201 has been identified in more than 95% of all published reports of FD/MAS. The most frequent missense pathogenic variants are p.Arg201His and p.Arg201Cys [Lumbroso et al 2004]. Very infrequently, arginine is replaced by serine, glycine, or leucine. Rarely, missense variants at p.Gln227 have been reported [Idowu et al 2007].

There are ongoing experimental approaches to develop methods with increased sensitivity [Bianco et al 2000, Narumi et al 2013, de Sanctis et al 2017] that in the future may enable the use of peripheral blood lymphocytes (PBL) for pathogenic variant detection and also allow the quantification of the mutated to wild type cell ratio within the sample (as opposed to presence-absence in PCR-RFLP techniques):

Table 4.

Techniques to Detect GNAS Somatic Variants

MethodDetection Rate
BloodLesional tissue
Variant-specific amplification by polymerase chain reaction (PCR) &/or restriction enzyme digestion (RFLP) followed by directed sequencing of the variant loci 1~20%-30%~80%
PCR with peptide-nucleic acid probes 2 combined w/next-generation sequencing (PNA-NGS) 3~75%~100%
Co-amplification at lower denaturation temperature and allele-specific PCR-based TaqMan genotyping (real-time COLD-MAMA-PCR) 4~75%~100%

Recent studies implicate alternate transcripts of GNAS in the pathogenesis of FD/MAS. A p.Arg543His variant, corresponding to position p.Arg201His in Gαs, on the large XLαs transcript of Gαs, was detected in individuals with a paternal pathogenic variant, whereas mutated neuroendocrine secretory protein 55 (NESP55) variant transcript was detected in those with a maternal pathogenic variant in the affected tissues. Functional in vitro assays of wild type XLαs showed strong induction of adenyl cyclase activity in transfected cells, suggesting that this GNAS variant could be playing a role in the pathogenesis of FD [Mariot et al 2011].

Table 5.

GNAS Somatic Variants Discussed in This GeneReview

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
c.601C>Tp.Arg201Cys NM_000516​.4

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Normal gene product. GNAS encodes the cAMP pathway-associated G-protein, Gsα. Gsα is a key component of many hormonal and other signal transduction pathways. Its primary role is to couple G-coupled protein receptors to adenylyl cyclase, promoting receptor-stimulated production of intracellular cAMP. Gsα in its inactive state forms a heterotrimer with the Gsβ and Gsγ subunits, with GDP bound to its binding site. Ligand binding to the G-coupled protein receptor promotes release of GDP from the α-subunit and binding of GTP. The GTP-bound Gsα dissociates from the β-γ heterotrimer and translocates to interact with adenylyl cyclase to promote cAMP production. Intrinsic GTPase hydrolyzes the bound GTP to GDP, leading to cessation of cAMP generation and reassembly of the α-β-γ heterotrimer. Downstream, cAMP is metabolized to AMP by one of many tissue-dependent phosphodiesterases.

Abnormal gene product. The FD/MAS-associated GNAS variants at residues p.Arg201 and p.Gln227 disrupt the activity of intrinsic GTPase, causing constitutive activity and inappropriately increased cAMP signaling [Landis et al 1989].

The spectrum of FD/MAS ranges from asymptomatic incidental findings to neonatal lethality. The phenotype of FD/MAS is a reflection of the role of Gsα in that tissue and whether or not a given tissue harbors a pathogenic variant in GNAS. The distribution of affected tissues is a reflection of the timing of the occurrence of the sporadic pathogenic variant during development and the fate of the specific clone in which the pathogenic variant occurs. It is likely that the stem cells of certain tissues will not tolerate mutated Gsα and are eliminated during development. Therefore, some tissues in which there is significant Gsα signaling will not be affected. For example, Gsα signaling is important in growth plate development, yet the growth plate is virtually never affected.

Activating or gain-of-function GNAS pathogenic variants in individuals with FD/MAS are present in the mosaic state, resulting from postzygotic somatic pathogenic variants appearing early in the course of development, which yields a monoclonal population of mutated cells within variously affected tissues. The non-mosaic state for most activating pathogenic variants is presumably lethal to the embryo (modified from OMIM 174800).

Cancer and Benign Tumors

The FD/MAS-associated activating GNAS pathogenic variants at residues p.Arg201 and p.Gln227 (collectively referred to as the gsp oncogene) have been reported in nonsyndromic benign [Landis et al 1989] and malignant [Wood et al 2007] tumors. However, the presence of the GNAS pathogenic variant alone is insufficient for malignant transformation of the affected tissues, but more likely predisposes for additional genetic or epigenetic events.

Chapter Notes

Author Notes

Alison M Boyce, MD is a pediatric endocrinologist who specializes in the evaluation and treatment of bone disorders in children and adolescents. She performs clinical research in FD/MAS and other pediatric skeletal diseases at the National Institutes of Health.

Pablo Florenzano, MD is an endocrinologist who specializes in the evaluation and treatment of bone disorders in adults. He performs clinical research at Pontificia Universidad Catolica de Chile, primarily in disorders of bone and mineral homeostasis.

Luis Fernandez de Castro Diaz, PhD is a staff scientist in the Skeletal Disorders and Mineral Homeostasis Section. He performs basic and translational research primarily in disorders of bone and mineral homeostasis.

Michael T Collins, MD is an endocrinologist who conducts translation research at the National Institutes of Health. He studies and treats primarily patients with rare disorders of bone and mineral homeostasis, including FD/MAS.


This research was supported by the Intramural Research Program of the NIH, NIDCR (AMB, MTC) and the Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Health System (AMB). The authors are grateful to the patients and their families for participation in the research and the efforts of the trainees of the NIH Interinstitute Endocrine Training Program for the excellent care they provide to our research subjects at the NIH Mark O Hatfield Clinical Research Center.

Revision History

  • 27 June 2019 (ma) Revision: Management section
  • 16 August 2018 (ma) Comprehensive update posted live
  • 26 February 2015 (me) Review posted live
  • 17 October 2014 (amb) Original submission


Literature Cited

  • Amit M, Collins MT, FitzGibbon EJ, Butman JA, Fliss DM, Gil Z. Surgery versus watchful waiting in patients with craniofacial fibrous dysplasia--a meta-analysis. PLoS One. 2011;6:e25179. [PMC free article: PMC3179490] [PubMed: 21966448]
  • Benhamou J, Gensburger D, Chapurlat R. Transient improvement of severe pain from fibrous dysplasia of bone with denosumab treatment. Joint Bone Spine. 2014;81:549–50. [PubMed: 24962974]
  • Bhattacharyya N, Wiench M, Dumitrescu C, Connolly BM, Bugge TH, Patel HV, Gafni RI, Cherman N, Cho M, Hager GL, Collins MT. Mechanism of FGF23 processing in fibrous dysplasia. J Bone Miner Res. 2012;27:1132–41. [PMC free article: PMC7448291] [PubMed: 22247037]
  • Bianco P, Riminucci M, Majolagbe A, Kuznetsov SA, Collins MT, Mankani MH, Corsi A, Bone HG, Wientroub S, Spiegel AM, Fisher LW, Robey PG. Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone. J Bone Miner Res. 2000;15:120–8. [PubMed: 10646121]
  • Boyce AM, Brewer C, DeKlotz TR, Zalewski CK, King KA, Collins MT, Kim HJ. Association of hearing loss and otologic outcomes with fibrous dysplasia. JAMA Otolaryngol Head Neck Surg. 2018;144:102–7. [PMC free article: PMC5839293] [PubMed: 29192304]
  • Boyce AM, Chong WH, Shawker TH, Pinto PA, Linehan WM, Bhattacharryya N, Merino MJ, Singer FR, Collins MT. Characterization and management of testicular pathology in McCune-Albright syndrome. J Clin Endocrinol Metab. 2012a;97:E1782–90. [PMC free article: PMC3431566] [PubMed: 22745241]
  • Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, Bassim C, Cherman N, Ellsworth M, Kasa-Vubu JZ, Farley FA, Molinolo AA, Bhattacharyya N, Collins MT. Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012b;27:1462–70. [PMC free article: PMC3377825] [PubMed: 22431375]
  • Boyce AM, Glover M, Kelly MH, Brillante BA, Butman JA, Fitzgibbon EJ, Brewer CC, Zalewski CK, Cutler Peck CM, Kim HJ, Collins MT. Optic neuropathy in McCune-Albright syndrome: effects of early diagnosis and treatment of growth hormone excess. J Clin Endocrinol Metab. 2013;98:E126–34. [PMC free article: PMC3537097] [PubMed: 23093488]
  • Boyce AM, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, Bianco P, Robey PG, Collins MT. A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. J Clin Endocrinol Metab. 2014;99:4133–40. [PMC free article: PMC4223439] [PubMed: 25033066]
  • Brown RJ, Kelly MH, Collins MT. Cushing syndrome in the McCune-Albright syndrome. J Clin Endocrinol Metab. 2010;95:1508–15. [PMC free article: PMC2853983] [PubMed: 20157193]
  • Carney JA, Young WF, Stratakis CA. Primary bimorphic adrenocortical disease: cause of hypercortisolism in McCune-Albright syndrome. Am J Surg Pathol. 2011;35:1311–26. [PMC free article: PMC4140081] [PubMed: 21836496]
  • Celi FS, Coppotelli G, Chidakel A, Kelly M, Brillante BA, Shawker T, Cherman N, Feuillan PP, Collins MT. The role of type 1 and type 2 5'-deiodinase in the pathophysiology of the 3,5,3'-triiodothyronine toxicosis of McCune-Albright syndrome. J Clin Endocrinol Metab. 2008;93:2383–9. [PMC free article: PMC2435649] [PubMed: 18349068]
  • Clark TJ, Tan BK, Kennedy CR. Asynchronous ovarian torsion in a patient with McCune-Albright syndrome. J Obstet Gynaecol. 2000;20:204. [PubMed: 15512529]
  • Collins MT, Chebli C, Jones J, Kushner H, Consugar M, Rinaldo P, Wientroub S, Bianco P, Robey PG. Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia. J Bone Miner Res. 2001;16:806–13. [PubMed: 11341325]
  • Collins MT, Kushner H, Reynolds JC, Chebli C, Kelly MH, Gupta A, Brillante B, Leet AI, Riminucci M, Robey PG, Bianco P, Wientroub S, Chen CC. An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone. J Bone Miner Res. 2005;20:219–26. [PubMed: 15647815]
  • Collins MT, Sarlis NJ, Merino MJ, Monroe J, Crawford SE, Krakoff JA, Guthrie LC, Bonat S, Robey PG, Shenker A. Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations. J Clin Endocrinol Metab. 2003;88:4413–7. [PubMed: 12970318]
  • Cox JL, Cushman-Vokoun AM, McGarry SV, Kozel JA. Two cases of Mazabraud syndrome and identification of a GNAS R201H mutation by next-generation sequencing. Virchows Arch. 2017;470:589–93. [PubMed: 28258512]
  • Cutler CM, Lee JS, Butman JA, FitzGibbon EJ, Kelly MH, Brillante BA, Feuillan P, Robey PG, DuFresne CR, Collins MT. Long-term outcome of optic nerve encasement and optic nerve decompression in patients with fibrous dysplasia: risk factors for blindness and safety of observation. Neurosurgery. 2006;59:1011–7. [PubMed: 17143235]
  • de Sanctis L, Galliano I, Montanari P, Matarazzo P, Tessaris D, Bergallo M. Combining real-time COLD- and MAMA-PCR TaqMan techniques to detect and quantify R201 GNAS mutations in the McCune-Albright syndrome. Horm Res Paediatr. 2017;87:342–9. [PubMed: 28334704]
  • Estrada A, Boyce AM, Brillante BA, Guthrie LC, Gafni RI, Collins MT. Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome. Eur J Endocrinol. 2016;175:477–83. [PMC free article: PMC5066167] [PubMed: 27562402]
  • Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with the McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. 2007;92:2100–6. [PubMed: 17405850]
  • Ganda K, Seibel MJ. Rapid biochemical response to denosumab in fibrous dysplasia of bone: report of two cases. Osteoporos Int. 2014;25:777–82. [PubMed: 24311113]
  • Gaujoux S, Salenave S, Ronot M, Rangheard AS, Cros J, Belghiti J, Sauvanet A, Ruszniewski P, Chanson P. Hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome. J Clin Endocrinol Metab. 2014;99:E97–101. [PubMed: 24170100]
  • Hansen MR, Moffat JC. Osteosarcoma of the skull base after radiation therapy in a patient with McCune-Albright syndrome: case report. Skull Base. 2003;13:79–83. [PMC free article: PMC1131834] [PubMed: 15912163]
  • Hart ES, Kelly MH, Brillante B, Chen CC, Ziran N, Lee JS, Feuillan P, Leet AI, Kushner H, Robey PG, Collins MT. Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome. J Bone Miner Res. 2007;22:1468–74. [PubMed: 17501668]
  • Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. J Community Genet. 2022;13:389–97. [PMC free article: PMC9314484] [PubMed: 35834113]
  • Idowu BD, Al-Adnani M, O'Donnell P, Yu L, Odell E, Diss T, Gale RE, Flanagan AM. A sensitive mutation-specific screening technique for GNAS1 mutations in cases of fibrous dysplasia: the first report of a codon 227 mutation in bone. Histopathology. 2007;50:691–704. [PubMed: 17493233]
  • Ikawa Y, Yachi Y, Inoue N, Kato A, Okajima M, Yachie A. Neonatal McCune-Albright syndrome with giant cell hepatitis. J Pediatr. 2016;178:298. [PubMed: 27592093]
  • Kalfa N, Philibert P, Audran F, Ecochard A, Hannon T, Lumbroso S, Sultan C. Searching for somatic mutations in McCune-Albright syndrome: a comparative study of the peptidic nucleic acid versus the nested PCR method based on 148 DNA samples. Eur J Endocrinol. 2006;155:839–43. [PubMed: 17132753]
  • Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:3933–51. [PubMed: 25356808]
  • Kelly MH, Brillante B, Collins MT. Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions. Osteoporos Int. 2008;19:57–63. [PubMed: 17622477]
  • Kelly MH, Brillante B, Kushner H, Gehron Robey P, Collins MT. Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone. Bone. 2005;37:388–94. [PubMed: 15963775]
  • Kuznetsov SA, Cherman N, Riminucci M, Collins MT, Robey PG, Bianco P. Age-dependent demise of GNAS-mutated skeletal stem cells and "normalization" of fibrous dysplasia of bone. J Bone Miner Res. 2008;23:1731–40. [PMC free article: PMC2585500] [PubMed: 18597624]
  • Lala R, Andreo M, Pucci A, Matarazzo P. Persistent hyperestrogenism after precocious puberty in young females with McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007;4 Suppl 4:423–8. [PubMed: 17982390]
  • Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989;340:692–6. [PubMed: 2549426]
  • Lawless ST, Reeves G, Bowen JR. The development of thyroid storm in a child with McCune-Albright syndrome after orthopedic surgery. Am J Dis Child. 1992;146:1099–102. [PubMed: 1514560]
  • Lee JS, FitzGibbon EJ, Chen YR, Kim HJ, Lustig LR, Akintoye SO, Collins MT, Kaban LB. Clinical guidelines for the management of craniofacial fibrous dysplasia. Orphanet J Rare Dis. 2012;7 Suppl 1:S2. [PMC free article: PMC3359960] [PubMed: 22640797]
  • Lee JS, FitzGibbon E, Butman JA, Dufresne CR, Kushner H, Wientroub S, Robey PG, Collins MT. Normal vision despite narrowing of the optic canal in fibrous dysplasia. N Engl J Med. 2002;347:1670–6. [PubMed: 12444181]
  • Leet AI, Boyce AM, Ibrahim KA, Wientroub S, Kushner H, Collins MT. Bone-grafting in polyostotic fibrous dysplasia. J Bone Joint Surg Am. 2016;98:211–9. [PMC free article: PMC4732545] [PubMed: 26842411]
  • Leet AI, Chebli C, Kushner H, Chen CC, Kelly MH, Brillante BA, Robey PG, Bianco P, Wientroub S, Collins MT. Fracture incidence in polyostotic fibrous dysplasia and the McCune-Albright syndrome. J Bone Miner Res. 2004a;19:571–7. [PubMed: 15005844]
  • Leet AI, Magur E, Lee JS, Wientroub S, Robey PG, Collins MT. Fibrous dysplasia in the spine: prevalence of lesions and association with scoliosis. J Bone Joint Surg Am. 2004b;86:531–7. [PubMed: 14996879]
  • Lim YH, Ovejero D, Sugarman JS, Deklotz CM, Maruri A, Eichenfield LF, Kelley PK, Jüppner H, Gottschalk M, Tifft CJ, Gafni RI, Boyce AM, Cowen EW, Bhattacharyya N, Guthrie LC, Gahl WA, Golas G, Loring EC, Overton JD, Mane SM, Lifton RP, Levy ML, Collins MT, Choate KA. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia. Hum Mol Genet. 2014;23:397–407. [PMC free article: PMC3869357] [PubMed: 24006476]
  • Liu F, Li W, Yao Y, Li G, Yang Y, Dou W, Zhong D, Wang L, Zhu X, Hu H, Zhang J, Wang R, Chen G. A case of McCune-Albright syndrome associated with pituitary GH adenoma: therapeutic process and autopsy. J Pediatr Endocrinol Metab. 2011;24:283–7. [PubMed: 21823524]
  • Lumbroso S, Paris F, Sultan C., European Collaborative Study. Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome--a European Collaborative Study. J Clin Endocrinol Metab. 2004;89:2107–13. [PubMed: 15126527]
  • Mahdi AJ, Connor P, Thakur I. McCune-Albright syndrome-associated bone marrow failure and extramedullary haematopoeisis secondary to fibrous dysplasia. Br J Haematol. 2017;178:179. [PubMed: 28612379]
  • Majoor BC, Boyce AM, Bovée JV, Smit VT, Collins MT, Cleton-Jansen AM, Dekkers OM, Hamdy NA, Dijkstra PS, Appelman-Dijkstra NM. Increased risk of breast cancer at a young age in women with fibrous dysplasia. J Bone Miner Res. 2018a;33:84–90. [PubMed: 28856726]
  • Majoor BCJ, Andela CD, Quispel CR. Rotman M2, Dijkstra PDS, Hamdy NAT, Kaptein AA, Appelman-Dijkstra NM. Illness perceptions are associated with quality of life in patients with fibrous dysplasia. Calcif Tissue Int. 2018b;102:23–31. [PMC free article: PMC5760610] [PubMed: 29022055]
  • Mancini F, Corsi A, De Maio F, Riminucci M, Ippolito E. Scoliosis and spine involvement in fibrous dysplasia of bone. Eur Spine J. 2009;18:196–202.
  • Manjila S, Zender CA, Weaver J, Rodgers M, Cohen AR. Aneurysmal bone cyst within fibrous dysplasia of the anterior skull base: continued intracranial extension after endoscopic resections requiring craniofacial approach with free tissue transfer reconstruction. Childs Nerv Syst. 2013;29:1183–92. [PubMed: 23435492]
  • Mariot V, Wu JY, Aydin C, Mantovani G, Mahon MJ, Linglart A, Bastepe M. Potent constitutive cyclic AMP-generating activity of XLαs implicates this imprinted GNAS product in the pathogenesis of McCune-Albright syndrome and fibrous dysplasia of bone. Bone​. 2011;48:312-20.
  • Narumi S, Matsuo K, Ishii T, Tanahashi Y, Hasegawa T. Quantitative and sensitive detection of GNAS mutations causing McCune-Albright syndrome with next generation sequencing. PLoS One. 2013;8:e60525. [PMC free article: PMC3607597] [PubMed: 23536913]
  • Ovejero D, Lim YH, Boyce AM, Gafni RI, McCarthy E, Nguyen TA, Eichenfield LF, DeKlotz CM, Guthrie LC, Tosi LL, Thornton PS, Choate KA, Collins MT. Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment. Osteoporos Int. 2016;27:3615–26. [PMC free article: PMC6908308] [PubMed: 27497815]
  • Parvanescu A, Cros J, Ronot M, Hentic O, Grybek V, Couvelard A, Levy P, Chanson P, Ruszniewski P, Sauvanet A, Gaujoux S. Optic neuropathy in McCune-Albright syndrome: effects of early diagnosis and treatment of growth hormone excess. JAMA Surg. 2014;149:858–62. [PubMed: 24898823]
  • Paul SM, Gabor LR, Rudzinski S, Giovanni D, Boyce AM, Kelly MR, Collins MT. Disease severity and functional factors associated with walking performance in polyostotic fibrous dysplasia. Bone. 2014;60:41–7. [PMC free article: PMC3985279] [PubMed: 24316419]
  • Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest. 2003;112:683–92. [PMC free article: PMC182207] [PubMed: 12952917]
  • Robinson C, Boyce AM, Estrada A, Kleiner DE, Mathew R, Stanton R, Frangoul H, Collins MT. Bone marrow failure and extramedullary hematopoiesis in McCune-Albright syndrome. Osteoporos Int. 2018;29:237–41. [PMC free article: PMC6983319] [PubMed: 29071359]
  • Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26:1343–1421. [PubMed: 27521067]
  • Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer. 1994;73:1411–24. [PubMed: 8111708]
  • Salenave S, Boyce AM, Collins MT, Chanson P. Acromegaly and McCune-Albright syndrome. J Clin Endocrinol Metab. 2014;99:1955–69. [PMC free article: PMC4037730] [PubMed: 24517150]
  • Silva ES, Lumbroso S, Medina M, Gillerot Y, Sultan C, Sokal EM. Demonstration of McCune-Albright mutations in the liver of children with high gammaGT progressive cholestasis. J Hepatol. 2000;32:154–8. [PubMed: 10673080]
  • Stanton RP, Ippolito E, Springfield D, Lindaman L, Wientroub S, Leet A. The surgical management of fibrous dysplasia of bone. Orphanet J Rare Dis. 2012;7 Suppl 1:S1. [PMC free article: PMC3359959] [PubMed: 22640754]
  • Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K., et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183–97. [PubMed: 22687371]
  • Tessaris D, Corrias A, Matarazzo P, De Sanctis L, Wasniewska M, Messina MF, Vigone MC, Lala R. Thyroid abnormalities in children and adolescents with McCune-Albright syndrome. Horm Res Paediatr. 2012;78:151–7. [PubMed: 23006743]
  • Vortmeyer AO, Gläsker S, Mehta GU, Abu-Asab MS, Smith JH, Zhuang Z, Collins MT, Oldfield EH. Somatic GNAS mutation causes widespread and diffuse pituitary disease in acromegalic patients with McCune-Albright syndrome. J Clin Endocrinol Metab. 2012;97:2404–13. [PMC free article: PMC3791436] [PubMed: 22564667]
  • Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: normal and abnormal functions. Endocrinology. 2004;145:5459–64. [PubMed: 15331575]
  • Wood LD, Noë M, Hackeng W, Brosens LA, Bhaijee F, Debeljak M, Yu J, Suenaga M, Singhi AD, Zaheer A, Boyce A, Robinson C, Eshleman JR, Goggins MG, Hruban RH, Collins MT, Lennon AM, Montgomery EA. Patientes with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas. Virchows Arch. 2017;470:391–400. [PMC free article: PMC5376511] [PubMed: 28188442]
  • Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318:1108–13. [PubMed: 17932254]
Copyright © 1993-2023, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2023 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK274564PMID: 25719192


  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this page (1.8M)

Tests in GTR by Gene

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed
  • Gene
    Locus Links

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...