McCune-Albright syndrome
Encyclopedia
McCune–Albright syndrome, described in 1937 by Donovan James McCune and Fuller Albright, is a genetic disorder
of bones, skin pigmentation and hormonal problems along with premature puberty
.
there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth.
Polyostotic fibrous dysplasia has different levels of severity. For example one child may be entirely healthy with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age and have no unusual skin pigmentation. The complete opposite of that would be children who are diagnosed in early infancy with the obvious bone disease and obvious increased endocrine secretions from several glands.
Approximately 20-30% of fibrous dysplasias are polyostotic and two thirds of patients are polyostotic before the age of ten.
Polyostotic fibrous dysplasia is usually caused by mosaicism
for a mutation in a gene called GNAS1 (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide 1).
The syndrome shows a broad spectrum of severity. The disease frequently involves the skull
and facial bones, pelvis
, spine and shoulder girdle. The sites of involvement are the femur
(91%), tibia
(81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle
, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia.
mutation
of the gene
GNAS1
, which is involved in G-protein signalling. This mutation, often a mosaicism, prevents downregulation of cAMP
signalling.
an teen afflicted with the disease, Marlie Casseus
, underwent a 17-hour emergency surgical procedure to remove a 7 kg (16 pound) tumour-like growth of bone from her face. A series of operations at Holtz Children's Hospital in Miami, Florida
restored the child's face to a more normal proportion.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of bones, skin pigmentation and hormonal problems along with premature puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
.
Symptoms
It is suspected when two of the three following features are present:- (autonomous) endocrine hyperfunction such as precocious pubertyPrecocious pubertyAs a medical term, precocious puberty describes puberty occurring at an unusually early age. In most of these children, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is...
- Polyostotic fibrous dysplasiaPolyostotic fibrous dysplasiaPolyostotic fibrous dysplasia is a form of fibrous dysplasia affecting more than one bone.The McCune-Albright syndrome includes polyostotic fibrous dysplasia as part of its presentation....
- Unilateral Café-au-lait spots
Presentation
Within the syndromeSyndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth.
Polyostotic fibrous dysplasia has different levels of severity. For example one child may be entirely healthy with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age and have no unusual skin pigmentation. The complete opposite of that would be children who are diagnosed in early infancy with the obvious bone disease and obvious increased endocrine secretions from several glands.
Approximately 20-30% of fibrous dysplasias are polyostotic and two thirds of patients are polyostotic before the age of ten.
Polyostotic fibrous dysplasia is usually caused by mosaicism
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
for a mutation in a gene called GNAS1 (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide 1).
The syndrome shows a broad spectrum of severity. The disease frequently involves the skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...
and facial bones, pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
, spine and shoulder girdle. The sites of involvement are the femur
Femur
The femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...
(91%), tibia
Tibia
The tibia , shinbone, or shankbone is the larger and stronger of the two bones in the leg below the knee in vertebrates , and connects the knee with the ankle bones....
(81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle
Clavicle
In human anatomy, the clavicle or collar bone is a long bone of short length that serves as a strut between the scapula and the sternum. It is the only long bone in body that lies horizontally...
, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia.
Genetics
Genetically, there is a post-zygoticZygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...
mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
GNAS1
GNAS1
GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit , a key component of many signal transduction pathways.- Gene :...
, which is involved in G-protein signalling. This mutation, often a mosaicism, prevents downregulation of cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
signalling.
Notable cases
The disease made headlines in December, 2005 when a HaitiHaiti
Haiti , officially the Republic of Haiti , is a Caribbean country. It occupies the western, smaller portion of the island of Hispaniola, in the Greater Antillean archipelago, which it shares with the Dominican Republic. Ayiti was the indigenous Taíno or Amerindian name for the island...
an teen afflicted with the disease, Marlie Casseus
Marlie Casseus
Marlie Casseus is a Haitian teenager who attracted national and international media attention when she received surgery to remove a 16-pound growth from her face that threatened her ability to eat, breathe, and see.-Background:...
, underwent a 17-hour emergency surgical procedure to remove a 7 kg (16 pound) tumour-like growth of bone from her face. A series of operations at Holtz Children's Hospital in Miami, Florida
Miami, Florida
Miami is a city located on the Atlantic coast in southeastern Florida and the county seat of Miami-Dade County, the most populous county in Florida and the eighth-most populous county in the United States with a population of 2,500,625...
restored the child's face to a more normal proportion.
External links
- Medterms.com
- GNAS gene
- NORD
- GFMER
- Fibrous Dysplasia Radiology Image Database