DMSMFH
MCID: DPH007
MIFTS: 37

Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma (DMSMFH)

Categories: Bone diseases, Cancer diseases, Fetal diseases, Genetic diseases, Muscle diseases, Rare diseases

Aliases & Classifications for Diaphyseal Medullary Stenosis with Malignant Fibrous...

MalaCards integrated aliases for Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

Name: Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma 57 12 20 72 13 15 70
Diaphyseal Medullary Stenosis-Bone Malignancy Syndrome 58 29 6
Bone Dysplasia with Malignant Fibrous Histiocytoma 57 20 72
Bone Dysplasia with Medullary Fibrosarcoma 57 20 72
Dmsmfh 57 20 72
Bdmf 57 20 72
Diaphyseal Medullary Stenosis-Malignant Fibrous Histiocytoma Syndrome 12 58
Bone Dysplasia-Medullary Fibrosarcoma Syndrome 12 58
Myopathy, Limb-Girdle, with Bone Fragility 57 20
Hardcastle Syndrome 12 58
Stenosis, Medullary, Diaphyseal, with Malignant Fibrous Histiocytoma 39
Bone Dysplasia with Medullary Fibrosarcoma; Bdmf 57
Limb-Girdle Myopathy with Bone Fragility 72
Dms-Mfh 72

Characteristics:

Orphanet epidemiological data:

58

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
mean age at onset of bone fractures, 24 years
mean age at onset of proximal muscle weakness, 31 years
not all patients have a myopathy
most become wheelchair-bound late in life


HPO:

31
diaphyseal medullary stenosis with malignant fibrous histiocytoma:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0080664
OMIM® 57 112250
NCIt 50 C122660
MESH via Orphanet 45 C536169
ICD10 via Orphanet 33 M89.8
UMLS via Orphanet 71 C1300202 C1862177
Orphanet 58 ORPHA85182
MedGen 41 C1862177
UMLS 70 C1862177

Summaries for Diaphyseal Medullary Stenosis with Malignant Fibrous...

OMIM® : 57 Diaphyseal medullary stenosis with malignant fibrous histiocytoma is an autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. In 2 families, affected individuals also showed a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. Thus, the disorder may be considered a tumor predisposition syndrome (summary by Camacho-Vanegas et al., 2012). (112250) (Updated 20-May-2021)

MalaCards based summary : Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma, also known as diaphyseal medullary stenosis-bone malignancy syndrome, is related to malignant fibrous histiocytoma and fibrous histiocytoma. An important gene associated with Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma is MTAP (Methylthioadenosine Phosphorylase). Affiliated tissues include bone and skeletal muscle, and related phenotypes are myopathy and premature graying of hair

Disease Ontology : 12 An osteochondrodysplasia that is characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis and that has material basis in heterozygous mutation in the MTAP gene on chromosome 9p21.

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85182 Definition Diaphyseal medullary stenosis with malignant fibrous histiocytoma is a very rare autosomal dominant bone dysplasia/ cancer syndrome characterized clinically by bone infarctions, cortical growth abnormalities, pathological fractures, and development of bone sarcoma (malignant fibrous histiocytoma).

UniProtKB/Swiss-Prot : 72 Diaphyseal medullary stenosis with malignant fibrous histiocytoma: An autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. Some patients show a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma.

Wikipedia : 73 Hardcastle syndrome is a rare genetic disorder on chromosome 9 at 9p22-p21. It affects the long bones.... more...

Related Diseases for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Diseases related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 malignant fibrous histiocytoma 10.5
2 fibrous histiocytoma 10.5
3 bone sarcoma 10.4
4 soft tissue sarcoma 10.4
5 myopathy 10.2
6 osteochondrodysplasia 10.1
7 osteoarthritis 10.0

Graphical network of the top 20 diseases related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:



Diseases related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma

Symptoms & Phenotypes for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Human phenotypes related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 myopathy 31 occasional (7.5%) HP:0003198
2 premature graying of hair 31 occasional (7.5%) HP:0002216
3 bruising susceptibility 31 occasional (7.5%) HP:0000978
4 thin skin 31 occasional (7.5%) HP:0000963
5 soft skin 31 occasional (7.5%) HP:0000977
6 osteopenia 31 HP:0000938
7 skeletal muscle atrophy 31 HP:0003202
8 osteosarcoma 31 HP:0002669
9 limb muscle weakness 31 HP:0003690
10 fractures of the long bones 31 HP:0003084
11 proximal muscle weakness 31 HP:0003701
12 patchy osteosclerosis 31 HP:0005686
13 pathologic fracture 31 HP:0002756
14 fibrosarcoma 31 HP:0100244
15 bowing of the legs 31 HP:0002979
16 histiocytoma 31 HP:0012315
17 stenosis of the medullary cavity of the long bones 31 HP:0100254
18 limb-girdle muscle weakness 31 HP:0003325
19 presenile cataracts 31 HP:0007819
20 metaphyseal striations 31 HP:0031367
21 osteomyelitis leading to amputation due to slow healing fractures 31 HP:0005010
22 diaphyseal cortical sclerosis 31 HP:0005045

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal:
osteopenia
radiolucency of the bones

Muscle Soft Tissue:
proximal muscle weakness
limb-girdle muscle weakness (2 families)
proximal and distal muscle atrophy
distal limb muscle weakness occurs later
myopathic changes seen on emg and muscle biopsy

Skeletal Limbs:
metaphyseal striations
osteomyelitis leading to amputation due to slow healing fractures
bony dysplasia
pathologic fractures of the long bones
patchy sclerotic changes to the long bones
more
Skin Nails Hair Hair:
premature graying (1 family)

Neoplasia:
osteosarcoma
fibrosarcoma
malignant fibrous histiocytoma (in about 35% of patients)

Head And Neck Eyes:
presenile cataracts

Skin Nails Hair Skin:
soft, thin skin (1 family)
easy bruising (1 family)

Laboratory Abnormalities:
serum alkaline phosphatase normal or mildly increased
serum creatine kinase normal or mildly increased

Clinical features from OMIM®:

112250 (Updated 20-May-2021)

Drugs & Therapeutics for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Study of Patients and Families With Diaphyseal Medullary Stenosis With Malignant Fibrous Histiocytoma of the Bone Completed NCT00007046

Search NIH Clinical Center for Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma

Genetic Tests for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Genetic tests related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

# Genetic test Affiliating Genes
1 Diaphyseal Medullary Stenosis-Bone Malignancy Syndrome 29 MTAP

Anatomical Context for Diaphyseal Medullary Stenosis with Malignant Fibrous...

MalaCards organs/tissues related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

40
Bone, Skeletal Muscle

Publications for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Articles related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

(show all 12)
# Title Authors PMID Year
1
Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts. 57 6 61
22464254 2012
2
Mapping autosomal dominant progressive limb-girdle myopathy with bone fragility to chromosome 9p21-p22: a novel locus for a musculoskeletal syndrome. 6 61 57
16244874 2005
3
Manifestations in a family with autosomal dominant bone fragility and limb-girdle myopathy. 6 57
16419137 2006
4
Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome. 6 57
8781110 1996
5
Hereditary bone dysplasia with malignant change. Report of three families. 57 6
3745248 1986
6
Hereditary bone dysplasia with sarcomatous degeneration. Study of a family. 57 6
4713573 1973
7
Abnormality of the long bones and progressive muscular dystrophy in a family. 6 57
13511301 1958
8
Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect. 57 61
10612808 2000
9
Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22. 57 61
10053015 1999
10
Fibrosarcoma complicating bone infarction in a caisson worker. A case report. 57
5218689 1966
11
Fibrosarcoma arising at the site of bone infarcts. A report of 2 cases. 57
13849880 1960
12
Diaphyseal medullary stenosis with malignant fibrous histiocytoma: further evidence for loss of heterozygosity involving 9p21-22 in tumor tissue. 61
11807991 2002

Variations for Diaphyseal Medullary Stenosis with Malignant Fibrous...

ClinVar genetic disease variations for Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

6 (show top 50) (show all 125)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MTAP MTAP, 885A-G, ARG100ARG SNV Pathogenic 29790 GRCh37:
GRCh38:
2 MTAP MTAP, IVS9AS, A-G, -2 SNV Pathogenic 29791 GRCh37:
GRCh38:
3 MTAP NM_002451.4(MTAP):c.*1608del Deletion Uncertain significance 366280 rs886063787 GRCh37: 9:21863621-21863621
GRCh38: 9:21863622-21863622
4 MTAP NM_002451.4(MTAP):c.300G>A (p.Glu100=) SNV Uncertain significance 366241 rs762121645 GRCh37: 9:21818154-21818154
GRCh38: 9:21818155-21818155
5 MTAP NM_002451.4(MTAP):c.*1831T>A SNV Uncertain significance 366286 rs886063789 GRCh37: 9:21863844-21863844
GRCh38: 9:21863845-21863845
6 MTAP NM_002451.4(MTAP):c.*2912G>C SNV Uncertain significance 366303 rs775831366 GRCh37: 9:21864925-21864925
GRCh38: 9:21864926-21864926
7 MTAP NM_002451.4(MTAP):c.-108_-103del Deletion Uncertain significance 366233 rs886063780 GRCh37: 9:21802640-21802645
GRCh38: 9:21802641-21802646
8 MTAP NM_002451.4(MTAP):c.*3389T>C SNV Uncertain significance 366312 rs765432220 GRCh37: 9:21865402-21865402
GRCh38: 9:21865403-21865403
9 MTAP NM_002451.4(MTAP):c.*102A>G SNV Uncertain significance 366253 rs755040797 GRCh37: 9:21862115-21862115
GRCh38: 9:21862116-21862116
10 MTAP NM_002451.4(MTAP):c.*2171G>A SNV Uncertain significance 366289 rs886063790 GRCh37: 9:21864184-21864184
GRCh38: 9:21864185-21864185
11 MTAP NM_002451.4(MTAP):c.*1197C>G SNV Uncertain significance 366275 rs886063786 GRCh37: 9:21863210-21863210
GRCh38: 9:21863211-21863211
12 MTAP NM_002451.4(MTAP):c.*1384G>C SNV Uncertain significance 366278 rs755911467 GRCh37: 9:21863397-21863397
GRCh38: 9:21863398-21863398
13 MTAP NM_002451.4(MTAP):c.*2837T>A SNV Uncertain significance 366301 rs566068002 GRCh37: 9:21864850-21864850
GRCh38: 9:21864851-21864851
14 MTAP NM_002451.4(MTAP):c.*258del Deletion Uncertain significance 366255 rs886063782 GRCh37: 9:21862263-21862263
GRCh38: 9:21862264-21862264
15 MTAP NM_002451.4(MTAP):c.*3943G>A SNV Uncertain significance 366318 rs886063794 GRCh37: 9:21865956-21865956
GRCh38: 9:21865957-21865957
16 MTAP NM_002451.4(MTAP):c.*3206C>T SNV Uncertain significance 366309 rs886063793 GRCh37: 9:21865219-21865219
GRCh38: 9:21865220-21865220
17 MTAP NM_002451.4(MTAP):c.*2383C>T SNV Uncertain significance 366295 rs886063791 GRCh37: 9:21864396-21864396
GRCh38: 9:21864397-21864397
18 MTAP NM_002451.4(MTAP):c.*2968T>C SNV Uncertain significance 366304 rs554780978 GRCh37: 9:21864981-21864981
GRCh38: 9:21864982-21864982
19 MTAP NM_002451.4(MTAP):c.*2606G>C SNV Uncertain significance 366298 rs886063792 GRCh37: 9:21864619-21864619
GRCh38: 9:21864620-21864620
20 MTAP NM_002451.4(MTAP):c.*3766C>T SNV Uncertain significance 366313 rs149649469 GRCh37: 9:21865779-21865779
GRCh38: 9:21865780-21865780
21 MTAP NM_002451.4(MTAP):c.*1140A>G SNV Uncertain significance 366273 rs886063785 GRCh37: 9:21863153-21863153
GRCh38: 9:21863154-21863154
22 MTAP NM_002451.4(MTAP):c.*378T>C SNV Uncertain significance 366259 rs886063783 GRCh37: 9:21862391-21862391
GRCh38: 9:21862392-21862392
23 MTAP NM_002451.4(MTAP):c.*1482A>G SNV Uncertain significance 366279 rs560361151 GRCh37: 9:21863495-21863495
GRCh38: 9:21863496-21863496
24 MTAP NM_002451.4(MTAP):c.*2638G>A SNV Uncertain significance 366299 rs556394357 GRCh37: 9:21864651-21864651
GRCh38: 9:21864652-21864652
25 MTAP NM_002451.4(MTAP):c.187A>G (p.Arg63Gly) SNV Uncertain significance 366240 rs886063781 GRCh37: 9:21818041-21818041
GRCh38: 9:21818042-21818042
26 MTAP NM_002451.4(MTAP):c.*3052C>T SNV Uncertain significance 366305 rs182636316 GRCh37: 9:21865065-21865065
GRCh38: 9:21865066-21865066
27 MTAP NM_002451.4(MTAP):c.*2651G>A SNV Uncertain significance 366300 rs569725867 GRCh37: 9:21864664-21864664
GRCh38: 9:21864665-21864665
28 MTAP NM_002451.4(MTAP):c.572C>T (p.Ala191Val) SNV Uncertain significance 638349 rs200708704 GRCh37: 9:21854751-21854751
GRCh38: 9:21854752-21854752
29 MTAP NM_002451.4(MTAP):c.*303G>A SNV Uncertain significance 912323 GRCh37: 9:21862316-21862316
GRCh38: 9:21862317-21862317
30 MTAP NM_002451.4(MTAP):c.*395A>G SNV Uncertain significance 912324 GRCh37: 9:21862408-21862408
GRCh38: 9:21862409-21862409
31 MTAP NM_002451.4(MTAP):c.*912A>G SNV Uncertain significance 913831 GRCh37: 9:21862925-21862925
GRCh38: 9:21862926-21862926
32 MTAP NM_002451.4(MTAP):c.*1093G>T SNV Uncertain significance 913832 GRCh37: 9:21863106-21863106
GRCh38: 9:21863107-21863107
33 MTAP NM_002451.4(MTAP):c.*2333C>G SNV Uncertain significance 913879 GRCh37: 9:21864346-21864346
GRCh38: 9:21864347-21864347
34 MTAP NM_002451.4(MTAP):c.*2481T>C SNV Uncertain significance 913880 GRCh37: 9:21864494-21864494
GRCh38: 9:21864495-21864495
35 MTAP NM_002451.4(MTAP):c.*254A>T SNV Uncertain significance 915054 GRCh37: 9:21862267-21862267
GRCh38: 9:21862268-21862268
36 MTAP NM_002451.4(MTAP):c.*3656A>G SNV Uncertain significance 913545 GRCh37: 9:21865669-21865669
GRCh38: 9:21865670-21865670
37 MTAP NM_002451.4(MTAP):c.*3501T>C SNV Uncertain significance 913544 GRCh37: 9:21865514-21865514
GRCh38: 9:21865515-21865515
38 MTAP NM_002451.4(MTAP):c.*3276A>G SNV Uncertain significance 913543 GRCh37: 9:21865289-21865289
GRCh38: 9:21865290-21865290
39 MTAP NM_002451.4(MTAP):c.*3160T>C SNV Uncertain significance 913542 GRCh37: 9:21865173-21865173
GRCh38: 9:21865174-21865174
40 MTAP NM_002451.4(MTAP):c.*2286A>G SNV Uncertain significance 913501 GRCh37: 9:21864299-21864299
GRCh38: 9:21864300-21864300
41 MTAP NM_002451.4(MTAP):c.*2269A>T SNV Uncertain significance 913500 GRCh37: 9:21864282-21864282
GRCh38: 9:21864283-21864283
42 MTAP NM_002451.4(MTAP):c.*1760A>G SNV Uncertain significance 366285 rs886063788 GRCh37: 9:21863773-21863773
GRCh38: 9:21863774-21863774
43 MTAP NM_002451.4(MTAP):c.-52G>C SNV Uncertain significance 914999 GRCh37: 9:21802696-21802696
GRCh38: 9:21802697-21802697
44 MTAP NM_002451.4(MTAP):c.*2183T>C SNV Uncertain significance 913498 GRCh37: 9:21864196-21864196
GRCh38: 9:21864197-21864197
45 MTAP NM_002451.4(MTAP):c.*795A>T SNV Uncertain significance 913450 GRCh37: 9:21862808-21862808
GRCh38: 9:21862809-21862809
46 MTAP NM_002451.4(MTAP):c.*730A>G SNV Uncertain significance 913449 GRCh37: 9:21862743-21862743
GRCh38: 9:21862744-21862744
47 MTAP NM_002451.4(MTAP):c.224A>G (p.Gln75Arg) SNV Uncertain significance 913413 GRCh37: 9:21818078-21818078
GRCh38: 9:21818079-21818079
48 MTAP NM_002451.4(MTAP):c.*3060A>G SNV Uncertain significance 912432 GRCh37: 9:21865073-21865073
GRCh38: 9:21865074-21865074
49 MTAP NM_002451.4(MTAP):c.*3057T>A SNV Uncertain significance 912431 GRCh37: 9:21865070-21865070
GRCh38: 9:21865071-21865071
50 MTAP NM_002451.4(MTAP):c.*2937C>G SNV Uncertain significance 912430 GRCh37: 9:21864950-21864950
GRCh38: 9:21864951-21864951

Expression for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Search GEO for disease gene expression data for Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma.

Pathways for Diaphyseal Medullary Stenosis with Malignant Fibrous...

GO Terms for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Sources for Diaphyseal Medullary Stenosis with Malignant Fibrous...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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