DMSMFH
MCID: DPH007
MIFTS: 31

Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma (DMSMFH)

Categories: Bone diseases, Cancer diseases, Fetal diseases, Genetic 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 58 54 76 30 13 6 74
Bone Dysplasia with Malignant Fibrous Histiocytoma 58 54 76
Bone Dysplasia with Medullary Fibrosarcoma 58 54 76
Dmsmfh 58 54 76
Bdmf 58 54 76
Myopathy, Limb-Girdle, with Bone Fragility 58 54
Diaphyseal Medullary Stenosis-Malignant Fibrous Histiocytoma Syndrome 60
Stenosis, Medullary, Diaphyseal, with Malignant Fibrous Histiocytoma 41
Diaphyseal Medullary Stenosis-Bone Malignancy Syndrome 60
Bone Dysplasia with Medullary Fibrosarcoma; Bdmf 58
Bone Dysplasia-Medullary Fibrosarcoma Syndrome 60
Limb-Girdle Myopathy with Bone Fragility 76
Hardcastle Syndrome 60
Dms-Mfh 76

Characteristics:

Orphanet epidemiological data:

60

OMIM:

58
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:

33
diaphyseal medullary stenosis with malignant fibrous histiocytoma:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Diaphyseal Medullary Stenosis with Malignant Fibrous...

OMIM : 58 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)

MalaCards based summary : Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma, also known as bone dysplasia with malignant fibrous histiocytoma, is related to malignant fibroxanthoma and histiocytoma. An important gene associated with Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma is MTAP (Methylthioadenosine Phosphorylase). Affiliated tissues include bone, skin and skeletal muscle, and related phenotypes are myopathy and thin skin

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 85182Disease definitionDiaphyseal medullary stenosis with malignant fibrous histiocytoma is a very rare autosomal dominant bone dysplasia/cancersyndrome characterized clinically by bone infarctions, cortical growth abnormalities, pathological fractures, and development of bone sarcoma (malignant fibrous histiocytoma).Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 76 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.

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 fibroxanthoma 10.5
2 histiocytoma 10.5
3 fibrous histiocytoma 10.5
4 undifferentiated pleomorphic sarcoma 10.5
5 myopathy 10.3

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:

33 (show all 22)
# Description HPO Frequency HPO Source Accession
1 myopathy 33 occasional (7.5%) HP:0003198
2 thin skin 33 occasional (7.5%) HP:0000963
3 premature graying of hair 33 occasional (7.5%) HP:0002216
4 bruising susceptibility 33 occasional (7.5%) HP:0000978
5 soft skin 33 occasional (7.5%) HP:0000977
6 osteopenia 33 HP:0000938
7 skeletal muscle atrophy 33 HP:0003202
8 pathologic fracture 33 HP:0002756
9 proximal muscle weakness 33 HP:0003701
10 osteosarcoma 33 HP:0002669
11 limb-girdle muscle weakness 33 HP:0003325
12 limb muscle weakness 33 HP:0003690
13 bowing of the legs 33 HP:0002979
14 fibrosarcoma 33 HP:0100244
15 patchy osteosclerosis 33 HP:0005686
16 fractures of the long bones 33 HP:0003084
17 stenosis of the medullary cavity of the long bones 33 HP:0100254
18 presenile cataracts 33 HP:0007819
19 osteomyelitis leading to amputation due to slow healing fractures 33 HP:0005010
20 metaphyseal striations 33 HP:0031367
21 diaphyseal cortical sclerosis 33 HP:0005045
22 histiocytoma 33 HP:0012315

Symptoms via clinical synopsis from OMIM:

58
Skeletal:
osteopenia
radiolucency of the bones

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

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

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

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

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 with Malignant Fibrous Histiocytoma 30 MTAP

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

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

42
Bone, Skin, Skeletal Muscle

Publications for Diaphyseal Medullary Stenosis with Malignant Fibrous...

Articles related to Diaphyseal Medullary Stenosis with Malignant Fibrous Histiocytoma:

# Title Authors Year
1
Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone cancer syndrome resulting from mutated retroviral-derived MTAP transcripts. ( 22464254 )
2012
2
Manifestations in a family with autosomal dominant bone fragility and limb-girdle myopathy. ( 16419137 )
2006
3
Mapping autosomal dominant progressive limb-girdle myopathy with bone fragility to chromosome 9p21-p22: a novel locus for a musculoskeletal syndrome. ( 16244874 )
2005
4
Diaphyseal medullary stenosis with malignant fibrous histiocytoma: further evidence for loss of heterozygosity involving 9p21-22 in tumor tissue. ( 11807991 )
2002
5
Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22. ( 10053015 )
1999
6
Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome. ( 8781110 )
1996
7
Hereditary bone dysplasia with malignant change. Report of three families. ( 3745248 )
1986
8
Hereditary bone dysplasia with sarcomatous degeneration. Study of a family. ( 4713573 )
1973
9
Abnormality of the long bones and progressive muscular dystrophy in a family. ( 13511301 )
1958

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 168)
# Gene Variation Type Significance SNP ID Assembly Location
1 MTAP MTAP, 885A-G, ARG100ARG single nucleotide variant Pathogenic
2 MTAP MTAP, IVS9AS, A-G, -2 single nucleotide variant Pathogenic
3 MTAP NM_002451.3(MTAP): c.*102A> G single nucleotide variant Uncertain significance rs755040797 GRCh38 Chromosome 9, 21862116: 21862116
4 MTAP NM_002451.3(MTAP): c.*102A> G single nucleotide variant Uncertain significance rs755040797 GRCh37 Chromosome 9, 21862115: 21862115
5 MTAP NM_002451.3(MTAP): c.*775dupA duplication Benign rs58147941 GRCh38 Chromosome 9, 21862789: 21862789
6 MTAP NM_002451.3(MTAP): c.*775dupA duplication Benign rs58147941 GRCh37 Chromosome 9, 21862788: 21862788
7 MTAP NM_002451.3(MTAP): c.*1140A> G single nucleotide variant Uncertain significance rs886063785 GRCh37 Chromosome 9, 21863153: 21863153
8 MTAP NM_002451.3(MTAP): c.*1140A> G single nucleotide variant Uncertain significance rs886063785 GRCh38 Chromosome 9, 21863154: 21863154
9 MTAP NM_002451.3(MTAP): c.-117T> C single nucleotide variant Likely benign rs545625466 GRCh37 Chromosome 9, 21802631: 21802631
10 MTAP NM_002451.3(MTAP): c.-117T> C single nucleotide variant Likely benign rs545625466 GRCh38 Chromosome 9, 21802632: 21802632
11 MTAP NM_002451.3(MTAP): c.*3851C> G single nucleotide variant Likely benign rs76751525 GRCh37 Chromosome 9, 21865864: 21865864
12 MTAP NM_002451.3(MTAP): c.*3851C> G single nucleotide variant Likely benign rs76751525 GRCh38 Chromosome 9, 21865865: 21865865
13 MTAP NM_002451.3(MTAP): c.*3829T> C single nucleotide variant Benign rs6475592 GRCh37 Chromosome 9, 21865842: 21865842
14 MTAP NM_002451.3(MTAP): c.*3829T> C single nucleotide variant Benign rs6475592 GRCh38 Chromosome 9, 21865843: 21865843
15 MTAP NM_002451.3(MTAP): c.*3766C> T single nucleotide variant Likely benign rs149649469 GRCh37 Chromosome 9, 21865779: 21865779
16 MTAP NM_002451.3(MTAP): c.*3766C> T single nucleotide variant Likely benign rs149649469 GRCh38 Chromosome 9, 21865780: 21865780
17 MTAP NM_002451.3(MTAP): c.*3307G> T single nucleotide variant Likely benign rs41270139 GRCh37 Chromosome 9, 21865320: 21865320
18 MTAP NM_002451.3(MTAP): c.*3307G> T single nucleotide variant Likely benign rs41270139 GRCh38 Chromosome 9, 21865321: 21865321
19 MTAP NM_002451.3(MTAP): c.*3144G> A single nucleotide variant Likely benign rs148910202 GRCh37 Chromosome 9, 21865157: 21865157
20 MTAP NM_002451.3(MTAP): c.*3144G> A single nucleotide variant Likely benign rs148910202 GRCh38 Chromosome 9, 21865158: 21865158
21 MTAP NM_002451.3(MTAP): c.*2873C> T single nucleotide variant Likely benign rs75664572 GRCh37 Chromosome 9, 21864886: 21864886
22 MTAP NM_002451.3(MTAP): c.*2873C> T single nucleotide variant Likely benign rs75664572 GRCh38 Chromosome 9, 21864887: 21864887
23 MTAP NM_002451.3(MTAP): c.*2638G> A single nucleotide variant Likely benign rs556394357 GRCh37 Chromosome 9, 21864651: 21864651
24 MTAP NM_002451.3(MTAP): c.*2638G> A single nucleotide variant Likely benign rs556394357 GRCh38 Chromosome 9, 21864652: 21864652
25 MTAP NM_002451.3(MTAP): c.*2606G> C single nucleotide variant Uncertain significance rs886063792 GRCh37 Chromosome 9, 21864619: 21864619
26 MTAP NM_002451.3(MTAP): c.*2606G> C single nucleotide variant Uncertain significance rs886063792 GRCh38 Chromosome 9, 21864620: 21864620
27 MTAP NM_002451.3(MTAP): c.*2522A> G single nucleotide variant Benign rs3802394 GRCh37 Chromosome 9, 21864535: 21864535
28 MTAP NM_002451.3(MTAP): c.*2522A> G single nucleotide variant Benign rs3802394 GRCh38 Chromosome 9, 21864536: 21864536
29 MTAP NM_002451.3(MTAP): c.*2365C> T single nucleotide variant Benign rs10117550 GRCh38 Chromosome 9, 21864379: 21864379
30 MTAP NM_002451.3(MTAP): c.*2365C> T single nucleotide variant Benign rs10117550 GRCh37 Chromosome 9, 21864378: 21864378
31 MTAP NM_002451.3(MTAP): c.*2255A> G single nucleotide variant Benign rs79020697 GRCh38 Chromosome 9, 21864269: 21864269
32 MTAP NM_002451.3(MTAP): c.*2255A> G single nucleotide variant Benign rs79020697 GRCh37 Chromosome 9, 21864268: 21864268
33 MTAP NM_002451.3(MTAP): c.*1729G> A single nucleotide variant Likely benign rs182527165 GRCh38 Chromosome 9, 21863743: 21863743
34 MTAP NM_002451.3(MTAP): c.*1729G> A single nucleotide variant Likely benign rs182527165 GRCh37 Chromosome 9, 21863742: 21863742
35 MTAP NM_002451.3(MTAP): c.*1622delA deletion Benign rs11358276 GRCh38 Chromosome 9, 21863636: 21863636
36 MTAP NM_002451.3(MTAP): c.*1622delA deletion Benign rs11358276 GRCh37 Chromosome 9, 21863635: 21863635
37 MTAP NM_002451.3(MTAP): c.*1608delC deletion Uncertain significance rs886063787 GRCh38 Chromosome 9, 21863622: 21863622
38 MTAP NM_002451.3(MTAP): c.*1608delC deletion Uncertain significance rs886063787 GRCh37 Chromosome 9, 21863621: 21863621
39 MTAP NM_002451.3(MTAP): c.*1384G> C single nucleotide variant Uncertain significance rs755911467 GRCh38 Chromosome 9, 21863398: 21863398
40 MTAP NM_002451.3(MTAP): c.*1384G> C single nucleotide variant Uncertain significance rs755911467 GRCh37 Chromosome 9, 21863397: 21863397
41 MTAP NM_002451.3(MTAP): c.*3943G> A single nucleotide variant Uncertain significance rs886063794 GRCh38 Chromosome 9, 21865957: 21865957
42 MTAP NM_002451.3(MTAP): c.*3943G> A single nucleotide variant Uncertain significance rs886063794 GRCh37 Chromosome 9, 21865956: 21865956
43 MTAP NM_002451.3(MTAP): c.*3361C> T single nucleotide variant Likely benign rs138870323 GRCh37 Chromosome 9, 21865374: 21865374
44 MTAP NM_002451.3(MTAP): c.*3361C> T single nucleotide variant Likely benign rs138870323 GRCh38 Chromosome 9, 21865375: 21865375
45 MTAP NM_002451.3(MTAP): c.*3093T> C single nucleotide variant Benign rs4977735 GRCh37 Chromosome 9, 21865106: 21865106
46 MTAP NM_002451.3(MTAP): c.*3093T> C single nucleotide variant Benign rs4977735 GRCh38 Chromosome 9, 21865107: 21865107
47 MTAP NM_002451.3(MTAP): c.*3072G> A single nucleotide variant Uncertain significance rs768885564 GRCh37 Chromosome 9, 21865085: 21865085
48 MTAP NM_002451.3(MTAP): c.*3072G> A single nucleotide variant Uncertain significance rs768885564 GRCh38 Chromosome 9, 21865086: 21865086
49 MTAP NM_002451.3(MTAP): c.*2968T> C single nucleotide variant Uncertain significance rs554780978 GRCh37 Chromosome 9, 21864981: 21864981
50 MTAP NM_002451.3(MTAP): c.*2968T> C single nucleotide variant Uncertain significance rs554780978 GRCh38 Chromosome 9, 21864982: 21864982

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...

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