Hereditary Multiple Exostoses malady

NIH Rare Diseases: Hereditary multiple osteochondromas (HMO) (formerly called hereditary multiple exostoses) is a genetic condition in which people develop multiple benign (noncancerous) bone tumors that are covered by cartilage (called osteochondromas). The number and location of osteochondromas varies greatly among affected individuals. These tumors are not present at birth, but almost all affected people develop multiple osteochondromas by the time they are 12 years old. Once the bones stop growing, the development of new osteochondromas also usually stops. Osteochondromas can cause abnormal growth of the arms, hands, and legs, which can lead to uneven limb lengths (limb length discrepancy) and short stature. These tumors may cause pain, limit joint movement, and exert pressure on nerves, blood vessels, and surrounding tissues. Osteochondromas are typically benign; however, researchers estimate that people with HMO have about a 1% lifetime risk of these tumors becoming a cancerous osteochondrosarcoma. HMO is caused by mutations in the EXT1 and EXT2 genes and is inherited in an autosomal dominant pattern.³⁰

MalaCards: Hereditary Multiple Exostoses, also known as hereditary multiple osteochondromas, is related to exostoses and enchondromatosis. An important gene associated with Hereditary Multiple Exostoses is EXTL3 (exostoses (multiple)-like 3), and among its related pathways are Signal transduction_AKT signaling and Signal transduction AKT signaling. The compound heparan sulfate have been mentioned in the context of this disorder. Affiliated tissues include colon and myeloid.

Disease Ontology: An exostosis that has material basis in a mutation on the genes ext1, ext2 and ext3 which results in multiple bony spurs throughout a child's growth.⁶

Genetics Home Reference: Hereditary multiple exostoses is a condition in which people develop multiple benign (noncancerous) bone tumors called exostoses. The number of exostoses and the bones on which they are located vary greatly among affected individuals. The exostoses are not present at birth, but approximately 96 percent of affected people develop multiple exostoses by the time they are 12 years old. Once people with hereditary multiple exostoses reach adult height and their bones stop growing, the development of new exostoses also usually stops.¹⁷

Wikipedia: Hereditary multiple exostoses (HME or MHE), also known as Diaphyseal aclasis, is a rare medical...⁴⁴ more...

GeneReviews summary for ext

Aliases & Descriptions:

hereditary multiple exostoses 6 44 15 30 16 17 hereditary multiple osteochondromas 15 30 16 multiple cartilaginous exostoses 15 16 17 diaphyseal aclasis 15 16 17 osteochondromatosis 17 43 osteochondromatosis syndrome (disorder) 6 exostoses, multiple hereditary 17 multiple congenital exostosis 6 hereditary multiple exostosis 30 exostoses multiple hereditary 32 multiple hereditary exostoses 17

multiple osteochondromatosis 17 multiple exostosis syndromes 6 multiple osteochondromas 17 neonatal hemochromatosis 43 cartilaginous exostosis 43 bessel-hagen disease 17 familial exostoses 17 multiple exostoses 30 exostoses 43 hme 16 hmo 30

Diseases related to hereditary multiple exostoses by text searches and GeneDecks gene sharing:

(show top 50)    (show all 164)

id	Related Disease	Score	Top Affiliating Genes
1	exostoses	31.4	MYC, GTDC2, EXT1, EXT2, EXT3, EXTL1
2	enchondromatosis	29.7	EXT1, EXT2
3	osteochondroma	29.6	EXT2, EXT1
4	ollier disease	29.6	EXT1, EXT2
5	exostosis	28.7	GALNT5, EXTL3, EXTL2, EXTL1, EXT2, EXT1
6	chondrosarcoma	28.5	EXT3, EXT2, EXT1, GTDC2
7	dysplasia epiphysealis hemimelica	12.9	EXT2, EXT1
8	secondary syphilis	12.7	EXT1, EXT2
9	colorectal cancer	10.3	MYC, GTDC2, EXT1, EXT2, EXTL3, GALNT5
10	neonatal hemochromatosis	9.2
11	carpotarsal osteochondromatosis	7.5
12	hemochromatosis	7.3
13	osteoporosis	7.2
14	acute myeloid leukemia	7.0
15	hereditary multiple osteochondromatosis, type i	7.0
16	hereditary multiple osteochondromatosis, type ii	7.0
17	leukemia	7.0
18	myeloid leukemia	7.0
19	osteosarcoma	7.0
20	trichorhinophalangeal syndrome type 2	7.0
21	exostoses, multiple, type 1	7.0
22	exostoses, multiple, type 2	7.0
23	exostoses, multiple, type 3	7.0
24	spasticity multiple exostoses	7.0
25	human monocytic ehrlichiosis	6.8
26	craniosynostosis exostoses nevus epibulbar dermoid	6.1
27	exostoses anetodermia brachydactyly type e	6.1
28	potocki-shaffer syndrome	6.1
29	hypertension	5.9
30	congenital aortic valve stenosis	5.9
31	congenital anosmia	5.9
32	congenital giant megaureter	5.9
33	congenitally corrected transposition of the great arteries	5.9
34	distichiasis heart congenital anomalies	5.9
35	infantile myofibromatosis	5.9
36	osteochondrodysplasia	5.9
37	congenital mitral regurgitation	5.9
38	congenital antithrombin deficiency	5.9
39	congenital human immunodeficiency virus	5.9
40	congenital fibrosis of the extraocular muscles 1a	5.9
41	distal congenital nonprogressive spinal muscular atrophy	5.9
42	intestinal pseudo-obstruction	5.9
43	phox2a-related congenital fibrosis of the extraocular muscles	5.9
44	actin-accumulation myopathy	5.9
45	congenital diaphragmatic hernia	5.9
46	congenital antithrombin deficiency type 2	5.9
47	congenital hypomyelination neuropathy	5.9
48	congenital fibrosis of the extraocular muscles 1b	5.9
49	esophageal atresia	5.9
50	kif21a-related congenital fibrosis of the extraocular muscles	5.9

Approved drugs:

Drug clinical trials:

MalaCards organs/tissues related to hereditary multiple exostoses:

²²

Articles related to hereditary multiple exostoses:

(show all 45)

id	Title	Authors	Year	Affiliating Genes
1	Novel EXT1 and EXT2 mutations in hereditary multiple exostoses families of Indian origin. (19309273)	Vanita V.... Singh J.R.	2009	EXT1, EXT2
2	Genetic analysis of hereditary multiple exostoses in Tunisian families: a novel frame-shift mutation in the EXT1 gene. (18330718)	Sfar S.... Chouchane L.	2009	EXT1
3	Identification of four novel EXT1 and EXT2 mutations in five Chinese pedigrees with hereditary multiple exostoses. (19839753)	Li Y.... Fu Q.	2009	EXT1, EXT2
4	Hereditary multiple exostoses and juvenile colon carc inoma: A case with a common genetic background? (19653241)	Pata G.... Salerni B.	2009	EXTL3
5	The molecular and cellular basis of exostosis formation in hereditary multiple exostoses. (18452536)	Trebicz-Geffen M.... Nevo Z.	2008	GTDC2
6	Hereditary multiple exostoses and enchondromatosis. (18328980)	Pannier S.... Legeai-Mallet L.	2008	EXT1, EXT2, GTDC2
7	A novel mutation in EXT2 gene in a Chinese family with hereditary multiple exostoses. (18666861)	Liu S.G.... Ma X.	2008	EXT2
8	Novel mutation in the EXT-1 gene in an Iranian family affected with hereditary multiple exostoses. (18810975)	Foroughmand A.M.... Mohammadi M.	2008	EXT1, EXT2
9	EXT1 and EXT2 mutation identified by denaturing high performance liquid chromatograph in three families with hereditary multiple exostoses (18067075)	Zhang M.... Ma X.	2007	EXT1, EXT2
10	Clinical outcome and genotype in patients with hereditary multiple exostoses. (17676624)	Jager M.... Krauspe R.	2007	EXT2, EXT1
11	A novel mutation in the EXT2 gene identified in two unrelated Chinese families with hereditary multiple exostoses. (18294062)	Liu S.G.... Ma X.	2007	EXT2
12	Denaturant gradient gel electrophoresis in the genetic diagnosis of hereditary multiple exostoses (17478946)	He H.B.... Li K.H.	2007	EXT3
13	Evaluation of the anatomic burden of patients with hereditary multiple exostoses. (17589361)	Alvarez C.M.... Casey B.	2007	EXT1, EXT2
14	Hereditary multiple exostoses. Molecular genetic analysis of the EXT1 gene in an unusual family (15739063)	Heinritz W.... Froster U.G.	2005	EXT1, EXT2
15	A mutation IVS2+1G>A in EXT2 gene causes hereditary multiple exostoses (15079787)	Hu Z.M.... Xia J.H.	2004	EXT2
16	Two-color multiplex ligation-dependent probe amplification: detecting genomic rearrangements in hereditary multiple exostoses. (15221792)	White S.J.... den Dunnen J.T.	2004	EXT1, EXT2
17	Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype-phenotype study. (15446535)	Porter D.E.... Simpson A.H.	2004	EXT1, EXT2
18	The short-lived exostosis induced surgically versus the lasting genetic hereditary multiple exostoses. (12645631)	Trebicz-Geffen M.... Robinson D.	2003	EXT1
19	Association of autism in two patients with hereditary multiple exostoses caused by novel deletion mutations of EXT1. (12032595)	Li H.... Momoi M.Y.	2002	EXT1
20	Intermediate grade osteosarcoma and chondrosarcoma arising in an osteochondroma. A case report of a patient with hereditary multiple exostoses. (11896078)	Bovee J.V.... Hogendoorn P.C.	2002	EXT2
21	From gene to disease; hereditary multiple exostoses (11845565)	Wuyts W.... Hogendoorn P.C.	2002	EXT2, EXT1, EXT3
22	Mutation screening of the EXT genes in patients with hereditary multiple exostoses in Taiwan. (12490068)	Shi Y.R.... Tsai F.J.	2002	EXT1, EXT2
23	Hereditary multiple exostoses and heparan sulfate polymerization. (12417417)	Zak B.M.... Esko J.D.	2002	EXT1, EXT2, EXTL1
24	Hereditary multiple exostoses: one center's experience and review of etiology. (12151882)	Pierz K.A.... Dormans J.P.	2002	EXT1
25	Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity. (11391482)	Cheung P.K.... Duncan G.	2001	EXT1, EXT2
26	A 651-665delinsTT mutation in EXT1 causes hereditary multiple exostoses. (11180615)	Shi Y.R.... Tsai C.H.	2001	EXT1
27	Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses. (11170095)	Seki H.... Fukushima Y.	2001	EXT1, EXT2
28	Genotype-phenotype correlation in hereditary multiple exostoses. (11432960)	Francannet C.... Legeai-Mallet L.	2001	EXT1, EXT2
29	Comparison of fluorescent single-strand conformation polymorphism analysis and denaturing high-performance liquid chromatography for detection of EXT1 and EXT2 mutations in hereditary multiple exostoses. (10713884)	Dobson-Stone C.... Monaco A.P.	2000	EXT1, EXT2
30	Hereditary multiple exostoses and acute myeloid leukemia: an unusual association. (11127404)	Gozdasoglu S.... Cin S.	2000	EXT1, EXT2
31	Association of EXT1 and EXT2, hereditary multiple exostoses gene products, in Golgi apparatus. (10679296)	Kobayashi S.... Shirasawa T.	2000	EXT1, EXT2, GTDC2
32	An R223P mutation in EXT2 gene causes hereditary multiple exostoses. (10738008)	Shi Y.-R.... Tsai C.-H.	2000	EXT2, EXT3
33	A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses. (10545594)	Simmons A.D.... Lovett M.	1999	EXT1, EXT2, TRAP1
34	Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses. (10429361)	Park K.J.... Park J.-G.	1999	EXT1, EXT2
35	Mutation analysis of hereditary multiple exostoses in the Chinese. (10480354)	Xu L.... Deng H.-X.	1999	EXT1, EXT2, EXTL2
36	A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online. (10671060)	Wolf M.... Knuutila S.	1998	EXT2
37	Evaluation of locus heterogeneity and EXT1 mutations in 34 families with hereditary multiple exostoses. (9521425)	Raskind W.H.... Houck J.	1998	EXT2, EXT1
38	A distamycin A-inducible fragile site, FRA8E, located in the region of the hereditary multiple exostoses gene, is not involved in HPV16 DNA integration and amplification. (9460496)	Hori T.... Imai T.	1998	MYC
39	Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses. (9463333)	Wuyts W.... Willems P.J.	1998	EXT1, EXT2
40	Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. (9326317)	Philippe C.... Monaco A.P.	1997	EXT2, EXT1
41	Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies. (8981950)	Hecht J.T.... Wells D.E.	1997	EXT1
42	Positional cloning of a gene involved in hereditary multiple exostoses. (8894688)	Wuyts W.... Willems P.J.	1996	EXT1, EXT2
43	Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). (7550340)	Ahn J.... Wells D.E.	1995	EXT1
44	A gene for hereditary multiple exostoses maps to chromosome 19p. (8081357)	Le Merrer M.... Maroteaux P.	1994	EXT3
45	Genetic heterogeneity in families with hereditary multiple exostoses. (8317501)	Cook A.... Schellenberg G.	1993	EXT1

Genes related to hereditary multiple exostoses according to GeneCards:

id	Symbol	Description	Score	GeneCards Section Context
1	EXTL3	exostoses (multiple)-like 3	11.1	Publications, Aliases & Descriptions, Orthologs
2	EXT3	exostoses (multiple) 3	11.0	Publications
3	EXT2	exostosin 2	11.0	Publications
4	EXTL1	exostoses (multiple)-like 1	11.0	Orthologs, Publications
5	EXT1	exostosin 1	11.0	Orthologs, Publications
6	EXTL2	exostoses (multiple)-like 2	11.0	Publications
7	GALNT5	UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 5 (GalNAc-T5)	11.0	Publications
8	TRAP1	TNF receptor-associated protein 1	11.0	Publications
9	MYC	v-myc myelocytomatosis viral oncogene homolog (avian)	11.0	Publications
10	GTDC2	glycosyltransferase-like domain containing 2	10.1	Publications

Pathways related to hereditary multiple exostoses according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Signal transduction_AKT signaling41	9.0	MYC, TRAP1
2	Signal transduction AKT signaling10	8.7	MYC, TRAP1
3	Glycosaminoglycan biosynthesis - heparan sulfate20	8.6	EXT1, EXT2, EXTL1, EXTL2, EXTL3
4	Metabolic pathways20	8.0	GALNT5, EXTL3, EXTL2, EXTL1, EXT2, EXT1

Compounds related to hereditary multiple exostoses according to GeneDecks:

id	Compound	Score	Top Affiliating Genes
1	heparan sulfate32 18	9.1	GTDC2, EXT1, EXT2, EXTL1, EXTL2, EXTL3

Cellular components related to hereditary multiple exostoses according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	endoplasmic reticulum	GO:005783	9.0	EXT1, EXT2, EXTL2, EXTL3
2	intrinsic to endoplasmic reticulum membrane	GO:031227	8.7	EXT2, EXTL1, EXTL2, EXTL3

Biological processes related to hereditary multiple exostoses according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	cellular polysaccharide biosynthetic process	GO:033692	9.8	EXT1, EXT2
2	ossification	GO:001503	9.7	EXT1, EXT2
3	heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process	GO:015014	9.6	EXT1, EXT2
4	glycosaminoglycan biosynthetic process	GO:006024	9.2	GALNT5, EXT2, EXT1
5	heparan sulfate proteoglycan biosynthetic process	GO:015012	9.1	EXT1, EXT2, EXTL2, EXTL3
6	protein glycosylation	GO:006486	9.0	EXT1, EXT2, EXTL1

Molecular functions related to hereditary multiple exostoses according to GeneDecks:

(show all 8)

id	Name	GO ID	Score	Top Affiliating Genes
1	N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity	GO:050509	9.8	EXT2, EXT1
2	heparan sulfate N-acetylglucosaminyltransferase activity	GO:042328	9.8	EXT2, EXT1
3	glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity	GO:001888	9.7	EXTL3, EXTL2
4	acetylglucosaminyltransferase activity	GO:008375	9.6	EXT1, EXT2
5	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity	GO:050508	9.5	EXT1, EXT2, EXTL1
6	glucuronosyltransferase activity	GO:015020	9.4	EXT2, EXT1
7	transferase activity, transferring glycosyl groups	GO:016757	9.3	GTDC2, EXT1, EXT2
8	protein heterodimerization activity	GO:046982	8.9	MYC, EXT1, EXT2