Introduction
Multiple Hereditary Exostoses (MHE), also often referred to as Hereditary Multiple Exostoses (HME), is a bone
disorder that affects mainly the long bones. Recently the term Multiple Osteochondroma (MO) was suggested
by the World Health Organization (WHO) as the preferred term to refer to this disorder and throughout this
article both abbreviations MHE / MO / HME will be used. MHE / MO / is characterized by the presence of bony
protuberances, which are described as osteochondromas or exostoses. They are located mainly near the
joints and are often accompanied by skeletal deformities.
MHE / MO / HME was first described in the year 1786, while the name multiple exostoses was first proposed
in 1876. In the literature one can find many other names describing this disorder; such as diaphyseal aclasis,
chondral osteoma, osteochondromata, multiple cartilaginous exostoses, (multiple) exostosis, deforming
chondreodysplasia, osteogenic disease, etc.
Single osteochondromas or exostoses are very common in the general human population (1 to 2%)but the
incidence of multiple osteochondroma is estimated to be 1 in 50,000. However, isolated communities have
been described where a much larger fraction of the population is affected. MHE / MO / HME is not a unique
human disease, as osteochondromas have been found in many species including cats, dogs, sheep, horses,
lizards, lions, etc. A large osteochondroma was even found on the bones of a dinosaur.
Clinical aspects
MHE / MO/ HME is a condition a person is born with and osteochondromas can be present at birth but in
most patients they are noticed within the first six years of life. By the age of 12, almost all patients have been
diagnosed. Most affected bones are the femur, tibia and fibula, but this is very variable from patient to
patient. In theory every bone which is formed by endochondral bone formation (a process of bone formation
in which cartilage is formed first, which then is replaced by bone) can be affected. Facial bones remain
normally unaffected. MHE / MO / HME is characterized by great variation in number, size, location and shape
of the osteochondromas, even within a family. The osteochondromas continue to grow until closure of the
growth plates at the end of puberty. Development of new osteochondromas or further growth at later age is
not common but has been described. In addition to the presence of the bony outgrowths, skeletal
deformities such as bowing and shortening of the forearm, knee, hip and ankle deformities can be present.
Mild short stature is also observed in many patients.
Many complications have been observed in MHE / MO / HME patients, including compression of tendons,
nerves, muscles, ligaments and spinal cord. The pressure of the osteochondromas on neighboring tissues
and organs causes often almost permanent pain. The most serious complication is the development of a
malignant tumor (a chondrosarcoma) out of an osteochondroma, mostly occurring at adult age. This event
is observed in 1 to 5% of the cases and is often preceded by abnormal growth of the osteochondroma or
changes in the cartilage cap which covers the osteochondroma. The only known treatments for MHE / MO /
HME are surgical removal of the osteochondromas, (which often grow back at the original site) and surgical
procedures to correct bone deformities and limb length discrepancies. Surgery, physical therapy and pain
management are currently the only options available to MHE / MO / HME patients, and their success varies
from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives. At
present there is no definite cure for MHE / MO / HME.
In addition to MO/MHE, two syndromes have been described where multiple exostoses are one of the
symptoms: the Langer-Giedion syndrome (LGS) and the Proximal 11p deletion syndrome (P11pDS). Patients
suffering from LGS have multiple osteochondromas, but also show typical characteristic features such as a
bulbous nose, protruding ears, sparse hair, cone-shaped epiphyses and often mental retardation. Patients
with P11pDS syndrome (also called Potocki-Shaffer syndrome) have multiple osteochondromas, skull defects
and often mental retardation.
Genetic aspects
MHE / MO / HME is an autosomal dominant hereditary disorder.This means that a patient with MHE / MO /
HME has a 50% chance of transmitting the disorder to his/her children, so he/she has a 50% chance that
his/her child will also have MHE / MO / HME and 50% that this is not the case. This is equal for both male
and female patients. Normally the disorder does not skip a generation. So if one of the parents does have
MHE / MO / HME and the child does not, this child will normally only have unaffected children. However, some
patients have very mild symptoms so it may only look like they are unaffected. In this case, their children are
still at 50% risk of developing MHE / MO / HME. This may create a situation where it seems that the disorder
skips a generation. In such cases, genetic analysis may reveal the true status. In a large number of patients
there is no previous family history of MHE / MO / HME and both parents are unaffected. In these patients a
new mutation has occurred. These patients have then again a 50% risk of transmitting the disorder to their
children.
To understand why MHE / MO / HME is an autosomal dominant disorder one has to understand the basic
principles of heredity. All our genetic information, which determines a great deal of the development of our
body, lies within our DNA. This DNA is organized in chromosomes, which are numbered from 1 to 22 while
the sex determining chromosomes are named X and Y. At the moment of conception, the egg cell which
comes from the mother fuses with the sperm cell, which is provided by the father. The egg cell contains 23
chromosomes (chromosome 1 to 22 and an X chromosome) and the sperm cell contains 23 chromosomes(1
to 22 and an X or Y chromosome). After fertilization, a fertilized egg with 46 chromosomes is formed from
which an embryo and eventually a human being will develop.
During this process the cells will divide with duplication of the DNA. Therefore, in the human body (almost)
every cell (with the exception of the egg and sperm cells) contains the 46 chromosomes containing the entire
DNA content. Males have one X and one Y chromosome, females have two X chromosomes. Certain parts of
our DNA, the so-called genes, contain all the information necessary to make proteins. Every gene is located
on a certain chromosome. If such gene contains an error, which is called a mutation, this can affect the
formation and/ or function of this gene and thus the function of the corresponding protein. Loss of altered
function of this protein can then result in a visible defect or disorder.
At present we know that there are two such genes, the EXT1 gene on chromosome 8 and the EXT2 gene
located on chromosome 11, which are important with respect to MHE / MO / HME. If a mutation in one of
these two genes occurs, this inactivates this gene and/or the corresponding EXT1 or EXT2 protein.
Therefore, MHE / MO / HME patients have only one functional EXT1 or EXT2 gene, so have only half of the
functional EXT1 or EXT2 proteins compared to people without a mutation in EXT1 or EXT2. Both EXT1 and
EXT2 have a function in cartilage and bone development and it appears that the remaining EXT proteins are
not enough for normal bone development. The fact that MHE / MO / HME patients still have one functional
EXT gene (and EXT protein) is not enough and therefore the effect of the mutation is dominant. This is in
contrast with the so-called recessive diseases, such as, for example, cystic fibrosis (CF) where you only
develop the disease if you have a mutation in both genes. People with a mutation in only one of their CF
genes do not get CF but are only carriers of the disease. The chance for two parents who are both carriers
of having an affected child is in this case 25%.
Approximately 60 to 70 % of MHE / MO / HME patients have a mutation in the EXT1 gene and 20 to 30%
have an EXT2 mutation. In 10 to 20% of the patients, no mutation is found. This can be explained by the
presence of a yet unknown, additional EXT-causing gene or by the fact that not all mutations can be
detected by the techniques commonly used in DNA diagnostics for MHE / MO / HME. The fact that most of the
families have a different mutation makes genetic analysis for MHE / MO / HME very laborious and expensive,
and it is therefore only performed in a few laboratories worldwide. At present, the outcome of genetic testing
has no effect on determining orthopeadic care but genetic testing may give more options in making choices
in reproduction. Once the mutation is identified in one patient, testing of family members is relatively easy
and it can confirm their affected/non-affected status. Moreover, presymptomatic and prenatal diagnostics
through chorionic villus sampling (CVS) at 10-12 weeks gestation or amniocentesis at 16-18 weeks
gestation is available and also preimplantation diagnostics (PGD) can be offered to those families for
whom the disease-causing mutation has been identified.
At present, it is still not very clear whether the differences in severity of the disease are related to whether
the patient has an EXT1 or EXT2 mutation. There seems to be a tendency that EXT1 mutations cause a
more severe type of MHE / MO / HME, but this needs to be confirmed in larger studies. In addition, there is no
explanation for the variation in severity that is observed between patients within one family, thus with the
same mutation. It is therefore at present impossible to make predictions with regard to severity of the
condition based upon mutation type.
Concluding remarks
Although still many questions remain unanswered, many aspects of MHE / MO / HME have been elucidated in
the past years. The increasing understanding of the genetic and biological aspects of this disorder will
increase the quality of the (genetic) counseling of MHE / MO / HME patients, which should always be offered
when a diagnosis of MHE / MO / HME is made.
Selected literature
1. Ahn J, Lüdecke H, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE: Cloning of the
putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genet. 1995, 11:137-143
2. Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK,
Powell CM, Shaffer LG, Willems PJ: Delineation of a contiguous gene syndrome with multiple exostoses,
enlarged parietal foramina, craniofacial dysostosis and mental retardation, caused by deletions on the short
arm of chromosome 11. Am J Hum Genet 1996, 58:734-742
3. Francannet C, Cohen-Tanugi A, Le MM, Munnich A, Bonaventure J, Legeai-Mallet L:
Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet 2001, 38:430-434
4. Hennekam RCM: Hereditary multiple exostoses. J Med Genet 1991, 28:262-266
5. Hunter J. The works of John Hunter, F.R.S. London: Longman, 1835.
6. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K: The putative tumor suppressors EXT1 and EXT2
are glycosyltranserases required for the biosynthesis of heparan sulfate. J Biol Chem. 1998,
273:26265-26268
7. Luckert Wicklund C, Pauli RM, Johnston D, Hecht JT: Natural history study of hereditary multiple
exostoses. Am J Med Genet 1995, 55:43-46
8. Lüdecke HJ, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ, Haan EA, Frydman M, Hamers
GJH, Wells DE, Horsthemke B: Molecular dissection of a ontiguous gene syndrome: localization of the genes
involved in the Langer-Giedion syndrome. Hum Mol Genet 1995, 4:31-36
9. McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F: The putative tumour
suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nature Genet. 1998, 19:158-161
10. McCormick C, Duncan G, Goutsos KT, Tufaro F: The putative tumor suppressors EXT1 and EXT2 form a
stable complex that accumulates in the golgi apparatus and catalyzes the synthesis of heparan sulfate. PNAS
2000, 97:668-673
11. Porter DE, Lonie L, Fraser M, Dobson-Stone C, Porter JR, Monaco AP, Simpson AH: Severity of disease
and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint
Surg Br 2004, 86:1041-6
12. Potocki L, Shaffer LG: Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion
syndrome involving the gene for hereditary multiple exostoses (EXT2). Am J Med Genet 1996, 62:319-325
13. Schmale GA, Conrad EU, Raskind WH: The natural history of hereditary multiple exostoses. 1994,
76:986-992
14. Solomon L: Hereditary multiple exostosis. J Bone Joint Surg (Br) 1963, 45:292-304
15. Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA: The
EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet 1996,
14:25-32
16. Vanhoenacker FM, Van HW, Wuyts W, Willems PJ, De SA: Hereditary multiple exostoses: from genetics
to clinical syndrome and complications. Eur J Radiol 2001, 40:208-217
17. Virchow R: Ueber the Entstehung des Enchondroms und seine Beziehungen zur Enchondrosis und
Exostosis cartilaginea. Monatsberichte der Koniglichen Preussischen Akademie der Wissenschaften 1876,
760
18. Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul E, De Boulle K, de Vries BBA,
Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet
L, van den Ouweland AMW, McGaughran J, Halley DJJ, Willems PJ: Positional cloning of a gene involved in
hereditary multiple exostoses. Human Molecular Genetics 1996, 5:1547-1557
19. Wuyts W, Van Hul W: Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.
Hum Mut 2000, 15:220-227
20. Wuyts W, Waeber G, Meinecke P, Schuler H, Goecke TO, Van Hul W, Bartsch O: Proximal 11p deletion
syndrome (P11pDS): additional evaluation of the clinical and molecular aspects. Eur J Hum Genet 2004,
12:400-6
21. Zak B, Crawford BE, Esko JD: Hereditary multiple exostoses and heparan sulfate polymerization.
Biochimica et Biophysica Acta 2002, 1573:346-355
Multiple Hereditary Exostoses (MHE), also often referred to as Hereditary Multiple Exostoses (HME), is a bone
disorder that affects mainly the long bones. Recently the term Multiple Osteochondroma (MO) was suggested
by the World Health Organization (WHO) as the preferred term to refer to this disorder and throughout this
article both abbreviations MHE / MO / HME will be used. MHE / MO / is characterized by the presence of bony
protuberances, which are described as osteochondromas or exostoses. They are located mainly near the
joints and are often accompanied by skeletal deformities.
MHE / MO / HME was first described in the year 1786, while the name multiple exostoses was first proposed
in 1876. In the literature one can find many other names describing this disorder; such as diaphyseal aclasis,
chondral osteoma, osteochondromata, multiple cartilaginous exostoses, (multiple) exostosis, deforming
chondreodysplasia, osteogenic disease, etc.
Single osteochondromas or exostoses are very common in the general human population (1 to 2%)but the
incidence of multiple osteochondroma is estimated to be 1 in 50,000. However, isolated communities have
been described where a much larger fraction of the population is affected. MHE / MO / HME is not a unique
human disease, as osteochondromas have been found in many species including cats, dogs, sheep, horses,
lizards, lions, etc. A large osteochondroma was even found on the bones of a dinosaur.
Clinical aspects
MHE / MO/ HME is a condition a person is born with and osteochondromas can be present at birth but in
most patients they are noticed within the first six years of life. By the age of 12, almost all patients have been
diagnosed. Most affected bones are the femur, tibia and fibula, but this is very variable from patient to
patient. In theory every bone which is formed by endochondral bone formation (a process of bone formation
in which cartilage is formed first, which then is replaced by bone) can be affected. Facial bones remain
normally unaffected. MHE / MO / HME is characterized by great variation in number, size, location and shape
of the osteochondromas, even within a family. The osteochondromas continue to grow until closure of the
growth plates at the end of puberty. Development of new osteochondromas or further growth at later age is
not common but has been described. In addition to the presence of the bony outgrowths, skeletal
deformities such as bowing and shortening of the forearm, knee, hip and ankle deformities can be present.
Mild short stature is also observed in many patients.
Many complications have been observed in MHE / MO / HME patients, including compression of tendons,
nerves, muscles, ligaments and spinal cord. The pressure of the osteochondromas on neighboring tissues
and organs causes often almost permanent pain. The most serious complication is the development of a
malignant tumor (a chondrosarcoma) out of an osteochondroma, mostly occurring at adult age. This event
is observed in 1 to 5% of the cases and is often preceded by abnormal growth of the osteochondroma or
changes in the cartilage cap which covers the osteochondroma. The only known treatments for MHE / MO /
HME are surgical removal of the osteochondromas, (which often grow back at the original site) and surgical
procedures to correct bone deformities and limb length discrepancies. Surgery, physical therapy and pain
management are currently the only options available to MHE / MO / HME patients, and their success varies
from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives. At
present there is no definite cure for MHE / MO / HME.
In addition to MO/MHE, two syndromes have been described where multiple exostoses are one of the
symptoms: the Langer-Giedion syndrome (LGS) and the Proximal 11p deletion syndrome (P11pDS). Patients
suffering from LGS have multiple osteochondromas, but also show typical characteristic features such as a
bulbous nose, protruding ears, sparse hair, cone-shaped epiphyses and often mental retardation. Patients
with P11pDS syndrome (also called Potocki-Shaffer syndrome) have multiple osteochondromas, skull defects
and often mental retardation.
Genetic aspects
MHE / MO / HME is an autosomal dominant hereditary disorder.This means that a patient with MHE / MO /
HME has a 50% chance of transmitting the disorder to his/her children, so he/she has a 50% chance that
his/her child will also have MHE / MO / HME and 50% that this is not the case. This is equal for both male
and female patients. Normally the disorder does not skip a generation. So if one of the parents does have
MHE / MO / HME and the child does not, this child will normally only have unaffected children. However, some
patients have very mild symptoms so it may only look like they are unaffected. In this case, their children are
still at 50% risk of developing MHE / MO / HME. This may create a situation where it seems that the disorder
skips a generation. In such cases, genetic analysis may reveal the true status. In a large number of patients
there is no previous family history of MHE / MO / HME and both parents are unaffected. In these patients a
new mutation has occurred. These patients have then again a 50% risk of transmitting the disorder to their
children.
To understand why MHE / MO / HME is an autosomal dominant disorder one has to understand the basic
principles of heredity. All our genetic information, which determines a great deal of the development of our
body, lies within our DNA. This DNA is organized in chromosomes, which are numbered from 1 to 22 while
the sex determining chromosomes are named X and Y. At the moment of conception, the egg cell which
comes from the mother fuses with the sperm cell, which is provided by the father. The egg cell contains 23
chromosomes (chromosome 1 to 22 and an X chromosome) and the sperm cell contains 23 chromosomes(1
to 22 and an X or Y chromosome). After fertilization, a fertilized egg with 46 chromosomes is formed from
which an embryo and eventually a human being will develop.
During this process the cells will divide with duplication of the DNA. Therefore, in the human body (almost)
every cell (with the exception of the egg and sperm cells) contains the 46 chromosomes containing the entire
DNA content. Males have one X and one Y chromosome, females have two X chromosomes. Certain parts of
our DNA, the so-called genes, contain all the information necessary to make proteins. Every gene is located
on a certain chromosome. If such gene contains an error, which is called a mutation, this can affect the
formation and/ or function of this gene and thus the function of the corresponding protein. Loss of altered
function of this protein can then result in a visible defect or disorder.
At present we know that there are two such genes, the EXT1 gene on chromosome 8 and the EXT2 gene
located on chromosome 11, which are important with respect to MHE / MO / HME. If a mutation in one of
these two genes occurs, this inactivates this gene and/or the corresponding EXT1 or EXT2 protein.
Therefore, MHE / MO / HME patients have only one functional EXT1 or EXT2 gene, so have only half of the
functional EXT1 or EXT2 proteins compared to people without a mutation in EXT1 or EXT2. Both EXT1 and
EXT2 have a function in cartilage and bone development and it appears that the remaining EXT proteins are
not enough for normal bone development. The fact that MHE / MO / HME patients still have one functional
EXT gene (and EXT protein) is not enough and therefore the effect of the mutation is dominant. This is in
contrast with the so-called recessive diseases, such as, for example, cystic fibrosis (CF) where you only
develop the disease if you have a mutation in both genes. People with a mutation in only one of their CF
genes do not get CF but are only carriers of the disease. The chance for two parents who are both carriers
of having an affected child is in this case 25%.
Approximately 60 to 70 % of MHE / MO / HME patients have a mutation in the EXT1 gene and 20 to 30%
have an EXT2 mutation. In 10 to 20% of the patients, no mutation is found. This can be explained by the
presence of a yet unknown, additional EXT-causing gene or by the fact that not all mutations can be
detected by the techniques commonly used in DNA diagnostics for MHE / MO / HME. The fact that most of the
families have a different mutation makes genetic analysis for MHE / MO / HME very laborious and expensive,
and it is therefore only performed in a few laboratories worldwide. At present, the outcome of genetic testing
has no effect on determining orthopeadic care but genetic testing may give more options in making choices
in reproduction. Once the mutation is identified in one patient, testing of family members is relatively easy
and it can confirm their affected/non-affected status. Moreover, presymptomatic and prenatal diagnostics
through chorionic villus sampling (CVS) at 10-12 weeks gestation or amniocentesis at 16-18 weeks
gestation is available and also preimplantation diagnostics (PGD) can be offered to those families for
whom the disease-causing mutation has been identified.
At present, it is still not very clear whether the differences in severity of the disease are related to whether
the patient has an EXT1 or EXT2 mutation. There seems to be a tendency that EXT1 mutations cause a
more severe type of MHE / MO / HME, but this needs to be confirmed in larger studies. In addition, there is no
explanation for the variation in severity that is observed between patients within one family, thus with the
same mutation. It is therefore at present impossible to make predictions with regard to severity of the
condition based upon mutation type.
Concluding remarks
Although still many questions remain unanswered, many aspects of MHE / MO / HME have been elucidated in
the past years. The increasing understanding of the genetic and biological aspects of this disorder will
increase the quality of the (genetic) counseling of MHE / MO / HME patients, which should always be offered
when a diagnosis of MHE / MO / HME is made.
Selected literature
1. Ahn J, Lüdecke H, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE: Cloning of the
putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genet. 1995, 11:137-143
2. Bartsch O, Wuyts W, Van Hul W, Hecht JT, Meinecke P, Hogue D, Werner W, Zabel B, Hinkel GK,
Powell CM, Shaffer LG, Willems PJ: Delineation of a contiguous gene syndrome with multiple exostoses,
enlarged parietal foramina, craniofacial dysostosis and mental retardation, caused by deletions on the short
arm of chromosome 11. Am J Hum Genet 1996, 58:734-742
3. Francannet C, Cohen-Tanugi A, Le MM, Munnich A, Bonaventure J, Legeai-Mallet L:
Genotype-phenotype correlation in hereditary multiple exostoses. J Med Genet 2001, 38:430-434
4. Hennekam RCM: Hereditary multiple exostoses. J Med Genet 1991, 28:262-266
5. Hunter J. The works of John Hunter, F.R.S. London: Longman, 1835.
6. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K: The putative tumor suppressors EXT1 and EXT2
are glycosyltranserases required for the biosynthesis of heparan sulfate. J Biol Chem. 1998,
273:26265-26268
7. Luckert Wicklund C, Pauli RM, Johnston D, Hecht JT: Natural history study of hereditary multiple
exostoses. Am J Med Genet 1995, 55:43-46
8. Lüdecke HJ, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ, Haan EA, Frydman M, Hamers
GJH, Wells DE, Horsthemke B: Molecular dissection of a ontiguous gene syndrome: localization of the genes
involved in the Langer-Giedion syndrome. Hum Mol Genet 1995, 4:31-36
9. McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F: The putative tumour
suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nature Genet. 1998, 19:158-161
10. McCormick C, Duncan G, Goutsos KT, Tufaro F: The putative tumor suppressors EXT1 and EXT2 form a
stable complex that accumulates in the golgi apparatus and catalyzes the synthesis of heparan sulfate. PNAS
2000, 97:668-673
11. Porter DE, Lonie L, Fraser M, Dobson-Stone C, Porter JR, Monaco AP, Simpson AH: Severity of disease
and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. J Bone Joint
Surg Br 2004, 86:1041-6
12. Potocki L, Shaffer LG: Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion
syndrome involving the gene for hereditary multiple exostoses (EXT2). Am J Med Genet 1996, 62:319-325
13. Schmale GA, Conrad EU, Raskind WH: The natural history of hereditary multiple exostoses. 1994,
76:986-992
14. Solomon L: Hereditary multiple exostosis. J Bone Joint Surg (Br) 1963, 45:292-304
15. Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA: The
EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet 1996,
14:25-32
16. Vanhoenacker FM, Van HW, Wuyts W, Willems PJ, De SA: Hereditary multiple exostoses: from genetics
to clinical syndrome and complications. Eur J Radiol 2001, 40:208-217
17. Virchow R: Ueber the Entstehung des Enchondroms und seine Beziehungen zur Enchondrosis und
Exostosis cartilaginea. Monatsberichte der Koniglichen Preussischen Akademie der Wissenschaften 1876,
760
18. Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul E, De Boulle K, de Vries BBA,
Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet
L, van den Ouweland AMW, McGaughran J, Halley DJJ, Willems PJ: Positional cloning of a gene involved in
hereditary multiple exostoses. Human Molecular Genetics 1996, 5:1547-1557
19. Wuyts W, Van Hul W: Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.
Hum Mut 2000, 15:220-227
20. Wuyts W, Waeber G, Meinecke P, Schuler H, Goecke TO, Van Hul W, Bartsch O: Proximal 11p deletion
syndrome (P11pDS): additional evaluation of the clinical and molecular aspects. Eur J Hum Genet 2004,
12:400-6
21. Zak B, Crawford BE, Esko JD: Hereditary multiple exostoses and heparan sulfate polymerization.
Biochimica et Biophysica Acta 2002, 1573:346-355
| The Genetics of Multiple Hereditary Exostoses A Simplified Explanation Wim Wuyts, Ph.D. Multiple Hereditary Exostoses - General aspects Click Here To View Informational Video Follow Up Companion To This Guide |
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HON Conduct 282463 and is linked on the NIH National Library of Medicine,
Directory of Health Organizations (SIS) website,as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease,
and the Intute: health & life sciences a free online service providing access to the
very best Web resources for education and research located in the UK
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium,
a European Commission granted Network of Excellence for studying the pathology
and genetics of bone tumors.
a European Commission granted Network of Excellence for studying the pathology
and genetics of bone tumors.
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