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Multiple congenital exostosis(EXT)

MedGen UID:
4612
Concept ID:
C0015306
Congenital Abnormality
Synonyms: EXT; Hereditary multiple exostoses; Hereditary multiple exostosis; Hereditary multiple osteochondromas; MULTIPLE CARTILAGINOUS EXOSTOSES; Multiple exostoses; Multiple osteochondromas
SNOMED CT: Hereditary multiple exostosis (254044004); Osteochondromatosis syndrome (254044004); Osteochondromatosis (254044004); Diaphyseal aclasia (254044004); Multiple osteochondromatosis (254044004); Multiple exostoses type I (254044004); Multiple congenital exostosis (254044004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related gene: EXT2
 
HPO: HP:0002762
Monarch Initiative: MONDO:0005508
OMIM®: 133700; 608177
OMIM® Phenotypic series: PS133700
Orphanet: ORPHA321

Disease characteristics

Excerpted from the GeneReview: Hereditary Multiple Osteochondromas
Hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas, benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%). [from GeneReviews]
Authors:
Wim Wuyts  |  Gregory A Schmale  |  Howard A Chansky, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Hereditary multiple osteochondromas is a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals. The osteochondromas are not present at birth, but approximately 96 percent of affected people develop multiple osteochondromas by the time they are 12 years old. Osteochondromas typically form at the end of long bones and on flat bones such as the hip and shoulder blade.

Multiple osteochondromas can disrupt bone growth and can cause growth disturbances of the arms, hands, and legs, leading to short stature. Often these problems with bone growth do not affect the right and left limb equally, resulting in uneven limb lengths (limb length discrepancy). Bowing of the forearm or ankle and abnormal development of the hip joints (hip dysplasia) caused by osteochondromas can lead to difficulty walking and general discomfort. Multiple osteochondromas may also result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas.

Osteochondromas are typically benign; however, in some instances these tumors become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 1 in 20 to 1 in 200 lifetime risk of developing cancerous osteochondromas (called sarcomas).  https://medlineplus.gov/genetics/condition/hereditary-multiple-osteochondromas

Clinical features

From HPO
Chondrosarcoma
MedGen UID:
3054
Concept ID:
C0008479
Neoplastic Process
A slowly growing malignant neoplasm derived from cartilage cells.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Madelung-like forearm deformities
MedGen UID:
342004
Concept ID:
C1851419
Finding
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Cervical myelopathy
MedGen UID:
57691
Concept ID:
C0149645
Disease or Syndrome
Peripheral nerve compression
MedGen UID:
343565
Concept ID:
C1851414
Finding
Multiple congenital exostosis
MedGen UID:
4612
Concept ID:
C0015306
Congenital Abnormality
Hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas, benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%).
Rib exostoses
MedGen UID:
322689
Concept ID:
C1835579
Finding
Multiple circumscribed bony excrescences located in the ribs.
Pelvic bone exostoses
MedGen UID:
335004
Concept ID:
C1844689
Neoplastic Process
A benign growth the projects outward from the bone surface of the pelvis. Exostoses are capped by cartilage, and arise from a bone that develops from cartilage.
Scapular exostoses
MedGen UID:
377019
Concept ID:
C1851415
Neoplastic Process
The presence of multiple exostoses on the scapula. An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage.
Protuberances at ends of long bones
MedGen UID:
342003
Concept ID:
C1851418
Finding
The presence of multiple protuberances (bulges, or knobs) at the ends of the long bones.

Conditions with this feature

Multiple congenital exostosis
MedGen UID:
4612
Concept ID:
C0015306
Congenital Abnormality
Hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas, benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%).
Leri-Weill dyschondrosteosis
MedGen UID:
75562
Concept ID:
C0265309
Disease or Syndrome
The phenotypic spectrum of SHOX deficiency disorders, caused by haploinsufficiency of the short stature homeobox-containing gene (SHOX), ranges from Leri-Weill dyschondrosteosis (LWD) at the severe end of the spectrum to nonspecific short stature at the mild end of the spectrum. In adults with SHOX deficiency, the proportion of LWD versus short stature without features of LWD is not well defined. In LWD the classic clinical triad is short stature, mesomelia, and Madelung deformity. Mesomelia, in which the middle portion of a limb is shortened in relation to the proximal portion, can be evident first in school-aged children and increases with age in frequency and severity. Madelung deformity (abnormal alignment of the radius, ulna, and carpal bones at the wrist) typically develops in mid-to-late childhood and is more common and severe in females. The phenotype of short stature caused by SHOX deficiency in the absence of mesomelia and Madelung deformity (called SHOX-deficient short stature in this GeneReview) is highly variable, even within the same family.
Metachondromatosis
MedGen UID:
98377
Concept ID:
C0410530
Disease or Syndrome
Metachondromatosis is characterized by exostoses (osteochondromas), commonly of the hands and feet, and enchondromas of long bone metaphyses and iliac crests (summary by Sobreira et al., 2010).
Potocki-Shaffer syndrome
MedGen UID:
318657
Concept ID:
C1832588
Disease or Syndrome
Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p12-p11.2 region and is characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses (168500), and biparietal foramina (609597) (summary by Swarr et al., 2010).
Multiple exostoses with spastic tetraparesis
MedGen UID:
371889
Concept ID:
C1834724
Disease or Syndrome
Exostoses, multiple, type III
MedGen UID:
333090
Concept ID:
C1838420
Disease or Syndrome
Exostoses, multiple, type 2
MedGen UID:
377018
Concept ID:
C1851413
Disease or Syndrome
Hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas, benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones. Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk for malignant degeneration is low (~2%-5%).
Exostoses-anetodermia-brachydactyly type E syndrome
MedGen UID:
338695
Concept ID:
C1851428
Disease or Syndrome
An association reported in a single kindred characterized by the variable presence of the following features: anetodermia (macular atrophy of the skin), multiple exostoses, and brachydactyly type E. There have been no further descriptions in the literature since 1985.
Polyposis, intestinal, with multiple exostoses
MedGen UID:
401357
Concept ID:
C1868005
Neoplastic Process
Wilms tumor, aniridia, genitourinary anomalies, intellectual disability, and obesity syndrome
MedGen UID:
382718
Concept ID:
C2675904
Disease or Syndrome
For a detailed discussion of the WAGR syndrome, see 194072. In a subgroup of individuals with the WAGR syndrome, obesity develops. The phenotype in this subset is associated with haploinsufficiency for the BDNF gene.

Professional guidelines

PubMed

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Recent clinical studies

Etiology

Sharif B, Lindsay D, Saifuddin A
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Best Pract Res Clin Rheumatol 2020 Jun;34(3):101505. Epub 2020 Apr 4 doi: 10.1016/j.berh.2020.101505. PMID: 32253147
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Ottaviani G, Jaffe N
Cancer Treat Res 2009;152:15-32. doi: 10.1007/978-1-4419-0284-9_2. PMID: 20213384

Diagnosis

Ellatif M, Sharif B, Lindsay D, Pollock R, Saifuddin A
Skeletal Radiol 2021 Oct;50(10):1941-1962. Epub 2021 Apr 1 doi: 10.1007/s00256-021-03770-3. PMID: 33791832
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Therapy

Ostetto F, Lana D, Tuzzato G, Staals E, Donati DM, Bianchi G
Hip Int 2023 Mar;33(2):161-168. Epub 2021 Jun 16 doi: 10.1177/11207000211025051. PMID: 34134547
Serra-Vinardell J, Roca-Ayats N, De-Ugarte L, Vilageliu L, Balcells S, Grinberg D
J Inherit Metab Dis 2020 Jan;43(1):133-144. Epub 2019 Apr 29 doi: 10.1002/jimd.12097. PMID: 30942483
Ottaviani G, Jaffe N
Cancer Treat Res 2009;152:15-32. doi: 10.1007/978-1-4419-0284-9_2. PMID: 20213384
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Prognosis

Bom F, Barbier O, Libouton X, Docquier PL
Orthop Traumatol Surg Res 2023 Sep;109(5):103445. Epub 2022 Oct 18 doi: 10.1016/j.otsr.2022.103445. PMID: 36270444
Laitinen MK, Evans S, Stevenson J, Sumathi V, Kask G, Jeys LM, Parry MC
Bone Joint J 2021 May;103-B(5):984-990. doi: 10.1302/0301-620X.103B5.BJJ-2020-1082.R2. PMID: 33934657
Sonne-Holm E, Wong C, Sonne-Holm S
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Bovée JV
Orphanet J Rare Dis 2008 Feb 13;3:3. doi: 10.1186/1750-1172-3-3. PMID: 18271966Free PMC Article

Clinical prediction guides

Ostetto F, Lana D, Tuzzato G, Staals E, Donati DM, Bianchi G
Hip Int 2023 Mar;33(2):161-168. Epub 2021 Jun 16 doi: 10.1177/11207000211025051. PMID: 34134547
Caino S, Cubilla MA, Alba R, Obregón MG, Fano V, Gómez A, Zecchini L, Lapunzina P, Aza-Carmona M, Heath KE, Asteggiano CG
Genes (Basel) 2022 Nov 7;13(11) doi: 10.3390/genes13112063. PMID: 36360300Free PMC Article
Wang W, Yang M, Shen Y, Chen K, Wu D, Yang C, Bai J, He D, Gao J
Mol Med Rep 2022 Apr;25(4) Epub 2022 Feb 25 doi: 10.3892/mmr.2022.12657. PMID: 35211766Free PMC Article
Cho YJ, Lee JY, Lee WG, Jung ST
Clin Orthop Surg 2020 Dec;12(4):549-553. Epub 2020 Nov 18 doi: 10.4055/cios19121. PMID: 33274034Free PMC Article
Ottaviani G, Jaffe N
Cancer Treat Res 2009;152:15-32. doi: 10.1007/978-1-4419-0284-9_2. PMID: 20213384

Recent systematic reviews

Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article
Sonne-Holm E, Wong C, Sonne-Holm S
Dan Med J 2014 Sep;61(9):A4895. PMID: 25186537

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