MCID: FML345
MIFTS: 45

Familial Expansile Osteolysis

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

Aliases & Classifications for Familial Expansile Osteolysis

MalaCards integrated aliases for Familial Expansile Osteolysis:

Name: Familial Expansile Osteolysis 53 49 55 71 28 51
Osteolysis, Familial Expansile 53 49 13
Mccabe Disease 53 49 55
Feo 53 49 71
Polyostotic Osteolytic Dysplasia, Hereditary Expansile 53 49
Expansile Osteolysis, Familial 53 49
Hepod 53 49
Eof 53 49
Polyostotic Osteolytic Dysplasia, Hereditary Expansile; Hepod 53
Hereditary Expansile Polyostotic Osteolytic Dysplasia 55
Expansile Osteolysis, Familial; Eof 53

Characteristics:

Orphanet epidemiological data:

55
familial expansile osteolysis
Inheritance: Autosomal dominant;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset of bone disease in second decade (range 18-44 years)
onset of hearing loss in childhood


HPO:

31
familial expansile osteolysis:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 174810
Orphanet 55 ORPHA85195
MESH via Orphanet 42 C536335
UMLS via Orphanet 70 C0432292
ICD10 via Orphanet 33 M89.5
MedGen 39 C0432292

Summaries for Familial Expansile Osteolysis

OMIM : 53 Familial expansile osteolysis is an autosomal dominant bone dysplasia characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton. There is medullary and cortical expansion of the bone without sclerosis, leading to painful and disabling deformities and tendency to pathologic fracture. Clinical features include onset of conductive hearing loss in childhood, premature loss of teeth, and variably increased serum alkaline phosphatase (summary by Palenzuela et al., 2002 and Elahi et al., 2007). (174810)

MalaCards based summary : Familial Expansile Osteolysis, also known as osteolysis, familial expansile, is related to osteogenic sarcoma and ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, and has symptoms including bone pain, bowing of the long bones and pathologic fracture. An important gene associated with Familial Expansile Osteolysis is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Development Endothelin-1/EDNRA signaling. Affiliated tissues include bone and cortex, and related phenotypes are hematopoietic system and immune system

UniProtKB/Swiss-Prot : 71 Familial expansile osteolysis: Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition.

Related Diseases for Familial Expansile Osteolysis

Diseases related to Familial Expansile Osteolysis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 46)
# Related Disease Score Top Affiliating Genes
1 osteogenic sarcoma 29.4 TNFRSF11B TNFSF11
2 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
3 gastric cancer 10.1
4 breast leiomyosarcoma 10.1 TNFRSF11A TNFSF11
5 aneurysmal bone cysts 10.1 TNFRSF11A TNFSF11
6 multicentric reticulohistiocytosis 10.0 TNFRSF11B TNFSF11
7 kummell's disease 10.0 TNFRSF11B TNFSF11
8 periodontitis, chronic 10.0 TNFRSF11B TNFSF11
9 chronic apical periodontitis 10.0 TNFRSF11B TNFSF11
10 bone cancer 10.0 TNFRSF11A TNFSF11
11 glucocorticoid-induced osteoporosis 10.0 TNFRSF11B TNFSF11
12 sarcoma 10.0
13 endosteal hyperostosis, autosomal dominant 10.0 TNFRSF11B TNFSF11
14 osteonecrosis 10.0 TNFRSF11B TNFSF11
15 spondyloarthropathy 1 9.9 TNFRSF11B TNFSF11
16 cholesteatoma 9.9 TNFRSF11B TNFSF11
17 bone inflammation disease 9.9 TNFRSF11B TNFSF11
18 bubonic plague 9.9
19 plague 9.9
20 otitis externa 9.9
21 aortic valve disease 2 9.9 TNFRSF11B TNFSF11
22 osteopetrosis 9.9 TNFRSF11A TNFSF11
23 synovitis 9.9 TNFRSF11B TNFSF11
24 periodontitis 9.9 TNFRSF11B TNFSF11
25 paget disease of bone 2, early-onset 9.9 SQSTM1 TNFRSF11A
26 arthropathy 9.8 TNFRSF11B TNFSF11
27 myeloma, multiple 9.8 TNFRSF11B TNFSF11
28 psoriatic arthritis 9.7 TNFRSF11B TNFSF11
29 polyarticular onset juvenile idiopathic arthritis 9.7 TNFRSF11A TNFRSF11B TNFSF11
30 hemophilic arthropathy 9.7 TNFRSF11A TNFRSF11B TNFSF11
31 paget disease of bone 5, juvenile-onset 9.7 TNFRSF11A TNFRSF11B TNFSF11
32 cohen-gibson syndrome 9.7 TNFRSF11A TNFRSF11B TNFSF11
33 multicentric carpotarsal osteolysis syndrome 9.7 TNFRSF11A TNFRSF11B TNFSF11
34 periapical periodontitis 9.6 TNFRSF11A TNFRSF11B TNFSF11
35 tooth resorption 9.6 TNFRSF11A TNFRSF11B TNFSF11
36 ischemic bone disease 9.6 TNFRSF11A TNFRSF11B TNFSF11
37 root resorption 9.6 TNFRSF11A TNFRSF11B TNFSF11
38 bone resorption disease 9.6 TNFRSF11A TNFRSF11B TNFSF11
39 bone remodeling disease 9.6 TNFRSF11A TNFRSF11B TNFSF11
40 giant cell tumor 9.6 TNFRSF11A TNFRSF11B TNFSF11
41 periodontal disease 9.6 TNFRSF11A TNFRSF11B TNFSF11
42 osteoporosis 9.6 TNFRSF11A TNFRSF11B TNFSF11
43 rheumatoid arthritis 9.6 TNFRSF11A TNFRSF11B TNFSF11
44 osteoarthritis 9.5 TNFRSF11B TNFSF11
45 periostitis 9.4 SQSTM1 TNFRSF11A TNFRSF11B
46 paget's disease of bone 9.1 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11

Graphical network of the top 20 diseases related to Familial Expansile Osteolysis:



Diseases related to Familial Expansile Osteolysis

Symptoms & Phenotypes for Familial Expansile Osteolysis

Symptoms via clinical synopsis from OMIM:

53
Skeletal Limbs:
bowing of the long bones
abnormal modeling, onset before focal disease (humerus, radius, ulna, tibia)
coarse 'fish net' bone trabeculae, onset before focal disease
rounded areas of trabecular loss (juxta-articular, metaphyseal, diaphyseal, early stage)
enlargement of affected area (intermediate stage)
more
Head And Neck Ears:
hearing loss, initially conductive, later mixed conductive-sensorineural
absence of middle ear ossicles (in some patients)

Laboratory Abnormalities:
elevated serum alkaline phosphatase
elevated urinary hydroxyproline

Skeletal:
pathologic fractures
severe bone pain
osteolytic lesions mainly affecting the appendicular skeleton
multinuclear osteoclasts
medullary expansion
more
Head And Neck Teeth:
resorption of cervical region of the teeth
progressive tooth mobility
spontaneous tooth fracture
early loss of dentition


Clinical features from OMIM:

174810

Human phenotypes related to Familial Expansile Osteolysis:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 bone pain 31 HP:0002653
2 bowing of the long bones 31 HP:0006487
3 pathologic fracture 31 HP:0002756
4 conductive hearing impairment 31 HP:0000405
5 osteolysis 31 HP:0002797
6 elevated alkaline phosphatase 31 HP:0003155
7 premature loss of teeth 31 HP:0006480
8 thin bony cortex 31 HP:0002753
9 fragile teeth 31 HP:0025124
10 hydroxyprolinuria 31 HP:0003080

MGI Mouse Phenotypes related to Familial Expansile Osteolysis:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.56 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
2 immune system MP:0005387 9.46 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
3 limbs/digits/tail MP:0005371 9.13 TNFRSF11A TNFRSF11B TNFSF11
4 skeleton MP:0005390 8.92 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11

Drugs & Therapeutics for Familial Expansile Osteolysis

Search Clinical Trials , NIH Clinical Center for Familial Expansile Osteolysis

Genetic Tests for Familial Expansile Osteolysis

Genetic tests related to Familial Expansile Osteolysis:

# Genetic test Affiliating Genes
1 Familial Expansile Osteolysis 28 TNFRSF11A

Anatomical Context for Familial Expansile Osteolysis

MalaCards organs/tissues related to Familial Expansile Osteolysis:

38
Bone, Cortex

Publications for Familial Expansile Osteolysis

Articles related to Familial Expansile Osteolysis:

(show all 18)
# Title Authors Year
1
Familial expansile osteolysis: An Australian case report of a Paget's Disease Mimic. ( 27258166 )
2016
2
Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association? ( 20168251 )
2010
3
Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. ( 18328984 )
2008
4
Familial expansile osteolysis--not exclusively an adult disorder. ( 16470392 )
2006
5
Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis. ( 15793411 )
2005
6
Identification of a novel tandem duplication in exon 1 of the TNFRSF11A gene in two unrelated patients with familial expansile osteolysis. ( 12568416 )
2003
7
Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene. ( 12362049 )
2002
8
Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred. ( 11889411 )
2002
9
Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. ( 11771666 )
2002
10
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. ( 10615125 )
2000
11
Conductive hearing loss caused by hereditary incus necrosis: a study of familial expansile osteolysis. ( 8643278 )
1996
12
Genetic linkage of familial expansile osteolysis to chromosome 18q. ( 7911698 )
1994
13
Familial expansile osteolysis: a morphological, histomorphometric and serological study. ( 1664226 )
1991
14
The radiographic features of familial expansile osteolysis. ( 2353208 )
1990
15
Dental abnormalities associated with familial expansile osteolysis: a clinical and radiographic study. ( 2216357 )
1990
16
Dental histology in familial expansile osteolysis. ( 2341974 )
1990
17
Familial expansile osteolysis. ( 2530018 )
1989
18
Familial expansile osteolysis. A new dysplasia. ( 3346299 )
1988

Variations for Familial Expansile Osteolysis

ClinVar genetic disease variations for Familial Expansile Osteolysis:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TNFRSF11A NM_003839.3(TNFRSF11A): c.46_63dup18 (p.Leu21_Ala22insLeuLeuCysAlaLeuLeu) duplication Pathogenic rs879253796 GRCh37 Chromosome 18, 59992631: 59992648
2 TNFRSF11A NM_003839.3(TNFRSF11A): c.45_62dup18 (p.Leu21_Ala22insLeuLeuCysAlaLeuLeu) duplication Pathogenic rs886037749 GRCh37 Chromosome 18, 59992630: 59992647

Expression for Familial Expansile Osteolysis

Search GEO for disease gene expression data for Familial Expansile Osteolysis.

Pathways for Familial Expansile Osteolysis

Pathways related to Familial Expansile Osteolysis according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.84 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
2
Show member pathways
12.22 TNFRSF11A TNFRSF11B TNFSF11
3
Show member pathways
12.18 TNFRSF11A TNFRSF11B TNFSF11
4
Show member pathways
11.85 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
5 11.79 TNFRSF11A TNFSF11
6 11.49 TNFRSF11A TNFSF11
7
Show member pathways
11.46 TNFRSF11A TNFRSF11B TNFSF11
8 11.45 TNFRSF11A TNFSF11
9
Show member pathways
11.36 SQSTM1 TNFRSF11A TNFSF11
10 11.09 TNFRSF11A TNFRSF11B TNFSF11
11 11.03 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
12 10.55 TNFRSF11B TNFSF11
13 10.34 TNFRSF11A TNFRSF11B TNFSF11

GO Terms for Familial Expansile Osteolysis

Biological processes related to Familial Expansile Osteolysis according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 response to lipopolysaccharide GO:0032496 9.51 TNFRSF11A TNFRSF11B
2 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.49 TNFRSF11A TNFSF11
3 positive regulation of DNA binding transcription factor activity GO:0051091 9.48 TNFRSF11A TNFSF11
4 ossification GO:0001503 9.46 TNFRSF11A TNFSF11
5 apoptotic signaling pathway GO:0097190 9.43 TNFRSF11A TNFRSF11B
6 tumor necrosis factor-mediated signaling pathway GO:0033209 9.43 TNFRSF11A TNFRSF11B TNFSF11
7 monocyte chemotaxis GO:0002548 9.4 TNFRSF11A TNFSF11
8 osteoclast differentiation GO:0030316 9.37 TNFRSF11A TNFSF11
9 mammary gland alveolus development GO:0060749 9.32 TNFRSF11A TNFSF11
10 TNFSF11-mediated signaling pathway GO:0071847 9.16 TNFRSF11A TNFSF11
11 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFRSF11A TNFSF11
12 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 8.62 TNFRSF11A TNFSF11

Molecular functions related to Familial Expansile Osteolysis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tumor necrosis factor-activated receptor activity GO:0005031 8.62 TNFRSF11A TNFRSF11B

Sources for Familial Expansile Osteolysis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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