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Diaphyseal medullary stenosis-bone malignancy syndrome(BDMF; DMSMFH)

MedGen UID:
350613
Concept ID:
C1862177
Disease or Syndrome
Synonyms: Bone dysplasia with malignant fibrous histiocytoma; Bone dysplasia with medullary fibrosarcoma; Diaphyseal medullary stenosis with malignant fibrous histiocytoma; MYOPATHY, LIMB-GIRDLE, WITH BONE FRAGILITY
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.
 
Gene (location): MTAP (9p21.3)
 
Monarch Initiative: MONDO:0007205
OMIM®: 112250
Orphanet: ORPHA85182

Definition

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). [from OMIM]

Clinical features

From HPO
Fibrosarcoma
MedGen UID:
5178
Concept ID:
C0016057
Neoplastic Process
A fibroblastic sarcoma is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells.
Osteosarcoma
MedGen UID:
10501
Concept ID:
C0029463
Neoplastic Process
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Histiocytoma
MedGen UID:
267592
Concept ID:
C1509147
Neoplastic Process
A neoplasm containing histiocytes.
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Limb-girdle muscle weakness
MedGen UID:
347625
Concept ID:
C1858127
Finding
Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Recurrent long bone fractures
MedGen UID:
66802
Concept ID:
C0240231
Finding
An increased tendency to fractures of the long bones (Mainly, the femur, tibia, fibula, humerus, radius, and ulna).
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Diaphyseal cortical sclerosis
MedGen UID:
322263
Concept ID:
C1833739
Finding
An elevation in bone density of the cortex of one or more diaphyses. Sclerosis is normally detected on a radiograph as an area of increased opacity.
Metaphyseal striations
MedGen UID:
376512
Concept ID:
C1849081
Finding
Longitudinal densities on radiographs located in a metaphysis (the narrow region of a long bone between the epiphysis and the diaphysis).
Patchy osteosclerosis
MedGen UID:
383784
Concept ID:
C1855845
Finding
Patchy (irregular) increase in bone density. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Stenosis of the medullary cavity of the long bones
MedGen UID:
867788
Concept ID:
C4022179
Disease or Syndrome
Bowing of the legs
MedGen UID:
1807399
Concept ID:
C5574706
Finding
A bending or abnormal curvature affecting a long bone of the leg.
Osteomyelitis leading to amputation due to slow healing fractures
MedGen UID:
351263
Concept ID:
C1864975
Finding
Premature graying of hair
MedGen UID:
75524
Concept ID:
C0263498
Finding
Development of gray hair at a younger than normal age.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpation of the skin.
Presenile cataracts
MedGen UID:
56349
Concept ID:
C0154971
Finding
Presenile cataract is a kind of cataract that occurs in early adulthood, that is, at an age that is younger than usual.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDiaphyseal medullary stenosis-bone malignancy syndrome
Follow this link to review classifications for Diaphyseal medullary stenosis-bone malignancy syndrome in Orphanet.

Recent clinical studies

Etiology

Jamil W, Allami MK, Mbakada N, Kluge W
Orthopedics 2009 Dec;32(12):916. doi: 10.3928/01477447-20091020-20. PMID: 19968223

Diagnosis

Panigrahi S, Patro BP, Mohapatra A, Patra SK
BMJ Case Rep 2021 Oct 28;14(10) doi: 10.1136/bcr-2021-244868. PMID: 34711623Free PMC Article
Cai Y, Lin H, Huang F, Zheng X, Huang Y, Zhang S
Medicine (Baltimore) 2018 Aug;97(33):e11725. doi: 10.1097/MD.0000000000011725. PMID: 30113457Free PMC Article
Jamil W, Allami MK, Mbakada N, Kluge W
Orthopedics 2009 Dec;32(12):916. doi: 10.3928/01477447-20091020-20. PMID: 19968223
Norton KI, Wagreich JM, Granowetter L, Martignetti JA
Pediatr Radiol 1996 Sep;26(9):675-7. doi: 10.1007/BF01356833. PMID: 8781110

Therapy

Cai Y, Lin H, Huang F, Zheng X, Huang Y, Zhang S
Medicine (Baltimore) 2018 Aug;97(33):e11725. doi: 10.1097/MD.0000000000011725. PMID: 30113457Free PMC Article

Clinical prediction guides

Cai Y, Lin H, Huang F, Zheng X, Huang Y, Zhang S
Medicine (Baltimore) 2018 Aug;97(33):e11725. doi: 10.1097/MD.0000000000011725. PMID: 30113457Free PMC Article
Watts GD, Mehta SG, Zhao C, Ramdeen S, Hamilton SJ, Novack DV, Mumm S, Whyte MP, Mc Gillivray B, Kimonis VE
Hum Genet 2005 Dec;118(3-4):508-14. Epub 2005 Oct 22 doi: 10.1007/s00439-005-0075-z. PMID: 16244874
Martignetti JA, Desnick RJ, Aliprandis E, Norton KI, Hardcastle P, Nade S, Gelb BD
Am J Hum Genet 1999 Mar;64(3):801-7. doi: 10.1086/302297. PMID: 10053015Free PMC Article

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