Diaphyseal medullary stenosis - bone malignancy

General Information (adopted from Orphanet):

Synonyms, Signs: DMSMFH
BONE DYSPLASIA WITH MEDULLARY FIBROSARCOMA
MYOPATHY, LIMB-GIRDLE, WITH BONE FRAGILITY
BONE DYSPLASIA WITH MALIGNANT FIBROUS HISTIOCYTOMA
BDMF
Hardcastle syndrome
Diaphyseal medullary stenosis - malignant fibrous histiocytoma
Bone dysplasia - medullary fibrosarcoma
Number of Symptoms 44
OrphanetNr: 85182
OMIM Id: 112250
ICD-10: M89.8
UMLs: C1300202
C1862177
MeSH: C536169
MedDRA:
Snomed: 389216001

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
[Orphanet]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic bone tumor
 -Rare genetic disease
Primary bone dysplasia with increased bone density
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare bone tumor
 -Rare bone disease
 -Rare oncologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0007819) Presenile cataracts 5 / 7739
2
 (HPO:0002669) Osteosarcoma 12 / 7739
3
 (HPO:0000938) Osteopenia 138 / 7739
4
 (HPO:0005686) Patchy osteosclerosis 3 / 7739
5
 (HPO:0002756) Pathologic fracture 30 / 7739
6
 (HPO:0005010) Osteomyelitis leading to amputation due to slow healing fractures 2 / 7739
7
 (HPO:0005045) Diaphyseal cortical sclerosis 2 / 7739
8
 (HPO:0003084) Fractures of the long bones 5 / 7739
9
 (HPO:0002979) Bowing of the legs 28 / 7739
10
 (HPO:0100254) Stenosis of the medullary cavity of the long bones 1 / 7739
11
 (HPO:0002216) Premature graying of hair rare [HPO:skoehler] 43 / 7739
12
 (HPO:0000977) Soft skin rare [HPO:skoehler] 23 / 7739
13
 (HPO:0000963) Thin skin rare [HPO:skoehler] 96 / 7739
14
 (HPO:0000978) Bruising susceptibility rare [HPO:skoehler] 123 / 7739
15
 (HPO:0012315) Histiocytoma 2 / 7739
16
 (HPO:0100244) Fibrosarcoma 6 / 7739
17
 (HPO:0003325) Limb-girdle muscle weakness 22 / 7739
18
 (HPO:0003202) Skeletal muscle atrophy 281 / 7739
19
 (HPO:0003701) Proximal muscle weakness 105 / 7739
20
 (HPO:0003198) Myopathy rare [HPO:skoehler] 151 / 7739
21
 (HPO:0003690) Limb muscle weakness 41 / 7739
22
 (OMIM) Narrow medullary cavities 1 / 7739
23
 (OMIM) Soft thin skin 3 / 7739
24
 (OMIM) Normal or mildly increased serum creatine kinase 6 / 7739
25
 (OMIM) Radiolucency of the bones 1 / 7739
26
 (OMIM) Marrow necrosis 1 / 7739
27
 (OMIM) Pathologic fractures of the long bones 1 / 7739
28
 (HPO:0003676) Progressive disorder 148 / 7739
29
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
30
 (OMIM) Diaphyseal medullary stenosis 1 / 7739
31
 (OMIM) Marrow infarctions 1 / 7739
32
 (OMIM) Serum alkaline phosphatase normal or mildly increased 1 / 7739
33
 (MedDRA:10025553) Fibrous histiocytomas malignant 1 / 7739
34
 (OMIM) Bony dysplasia 1 / 7739
35
 (OMIM) Muscle atrophy, proximal and distal 3 / 7739
36
 (OMIM) Coarse, sclerotic trabeculae 1 / 7739
37
 (OMIM) Necrosis in large tubular bone diaphyses 1 / 7739
38
 (OMIM) Myopathic changes seen on EMG and muscle biopsy 1 / 7739
39
 (OMIM) Distal limb muscle weakness occurs later 3 / 7739
40
 (MedDRA:10025552) Malignant fibrous histiocytoma 1 / 7739
41
 (OMIM) Patchy sclerotic changes to the long bones 1 / 7739
42
 (OMIM) Bowing of the lower extremities 1 / 7739
43
 (OMIM) Metaphyseal striations 2 / 7739
44
 (OMIM) Diaphyseal cortical thickening 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Arnold (1973) described several generations of a Vermont and New York kindred demonstrating multiple areas of necrosis in the diaphyses of the large tubular bones. The radiographic appearance of this skeletal condition resembled radiation osteitis, a highly premalignant ...
Molecular genetics OMIM Camacho-Vanegas et al. (2012) identified 2 different heterozygous mutations affecting exon 9 of the MTAP gene (156540.0001 and 156540.0002) in affected members of 5 unrelated families with diaphyseal medullary stenosis with malignant fibrous histiocytoma. Four of the families ...