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 57 53 59 75 37 29 55 6
Osteolysis, Familial Expansile 57 53 13 40
Mccabe Disease 57 53 59
Feo 57 53 75
Polyostotic Osteolytic Dysplasia, Hereditary Expansile 57 53
Expansile Osteolysis, Familial 57 53
Hepod 57 53
Eof 57 53
Polyostotic Osteolytic Dysplasia, Hereditary Expansile; Hepod 57
Hereditary Expansile Polyostotic Osteolytic Dysplasia 59
Expansile Osteolysis, Familial; Eof 57

Characteristics:

Orphanet epidemiological data:

59
familial expansile osteolysis
Inheritance: Autosomal dominant;

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
familial expansile osteolysis:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 174810
Orphanet 59 ORPHA85195
MESH via Orphanet 45 C536335
UMLS via Orphanet 74 C0432292
ICD10 via Orphanet 34 M89.5
MedGen 42 C0432292
KEGG 37 H02042

Summaries for Familial Expansile Osteolysis

OMIM : 57 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 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus and gastric cancer. An important gene associated with Familial Expansile Osteolysis is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are NF-kappa B signaling pathway and Osteoclast differentiation. Affiliated tissues include bone and cortex, and related phenotypes are bowing of the long bones and pathologic fracture

UniProtKB/Swiss-Prot : 75 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 43)
# Related Disease Score Top Affiliating Genes
1 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
2 gastric cancer 10.1
3 breast leiomyosarcoma 10.1 TNFRSF11A TNFSF11
4 aneurysmal bone cysts 10.1 TNFRSF11A TNFSF11
5 multicentric reticulohistiocytosis 10.0 TNFRSF11B TNFSF11
6 kummell's disease 10.0 TNFRSF11B TNFSF11
7 osteogenic sarcoma 10.0
8 sarcoma 10.0
9 periodontitis, chronic 10.0 TNFRSF11B TNFSF11
10 chronic apical periodontitis 10.0 TNFRSF11B TNFSF11
11 bone cancer 9.9 TNFRSF11A TNFSF11
12 glucocorticoid-induced osteoporosis 9.9 TNFRSF11B TNFSF11
13 endosteal hyperostosis, autosomal dominant 9.9 TNFRSF11B TNFSF11
14 bubonic plague 9.9
15 plague 9.9
16 otitis externa 9.9
17 osteonecrosis 9.9 TNFRSF11B TNFSF11
18 bone inflammation disease 9.8 TNFRSF11B TNFSF11
19 aortic valve disease 2 9.8 TNFRSF11B TNFSF11
20 paget disease of bone 2, early-onset 9.8 SQSTM1 TNFRSF11A
21 synovitis 9.8 TNFRSF11B TNFSF11
22 periostitis 9.7 SQSTM1 TNFRSF11A
23 arthropathy 9.7 TNFRSF11B TNFSF11
24 osteopetrosis 9.7 TNFRSF11A TNFSF11
25 periodontitis 9.7 TNFRSF11B TNFSF11
26 psoriatic arthritis 9.5 TNFRSF11B TNFSF11
27 polyarticular onset juvenile idiopathic arthritis 9.5 TNFRSF11A TNFRSF11B TNFSF11
28 hemophilic arthropathy 9.4 TNFRSF11A TNFRSF11B TNFSF11
29 paget disease of bone 5, juvenile-onset 9.4 TNFRSF11A TNFRSF11B TNFSF11
30 multicentric carpotarsal osteolysis syndrome 9.4 TNFRSF11A TNFRSF11B TNFSF11
31 periapical periodontitis 9.4 TNFRSF11A TNFRSF11B TNFSF11
32 tooth resorption 9.4 TNFRSF11A TNFRSF11B TNFSF11
33 ischemic bone disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
34 root resorption 9.4 TNFRSF11A TNFRSF11B TNFSF11
35 bone resorption disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
36 bone remodeling disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
37 giant cell tumor 9.4 TNFRSF11A TNFRSF11B TNFSF11
38 periodontal disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
39 bone disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
40 osteoporosis 9.3 TNFRSF11A TNFRSF11B TNFSF11
41 rheumatoid arthritis 9.2 TNFRSF11A TNFRSF11B TNFSF11
42 myeloma, multiple 9.2 TNFRSF11B TNFSF11
43 paget's disease of bone 8.5 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:

57
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:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 bowing of the long bones 32 HP:0006487
2 pathologic fracture 32 HP:0002756
3 conductive hearing impairment 32 HP:0000405
4 bone pain 32 HP:0002653
5 osteolysis 32 HP:0002797
6 elevated alkaline phosphatase 32 HP:0003155
7 thin bony cortex 32 HP:0002753
8 fragile teeth 32 HP:0025124
9 premature loss of teeth 32 HP:0006480
10 hydroxyprolinuria 32 HP:0003080

MGI Mouse Phenotypes related to Familial Expansile Osteolysis:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.56 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
2 craniofacial MP:0005382 9.5 TNFRSF11A TNFRSF11B TNFSF11
3 immune system MP:0005387 9.46 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
4 limbs/digits/tail MP:0005371 9.13 TNFRSF11A TNFRSF11B TNFSF11
5 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 29 TNFRSF11A

Anatomical Context for Familial Expansile Osteolysis

MalaCards organs/tissues related to Familial Expansile Osteolysis:

41
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 (excessive RANK effect) in a 5-generation American kindred. ( 11889411 )
2002
8
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
9
Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene. ( 12362049 )
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
Dental abnormalities associated with familial expansile osteolysis: a clinical and radiographic study. ( 2216357 )
1990
15
Dental histology in familial expansile osteolysis. ( 2341974 )
1990
16
The radiographic features of familial expansile osteolysis. ( 2353208 )
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.46_63dup18 (p.Leu21_Ala22insLeuLeuCysAlaLeuLeu) duplication Pathogenic rs879253796 GRCh38 Chromosome 18, 62325398: 62325415
3 TNFRSF11A NM_003839.3(TNFRSF11A): c.45_62dup18 (p.Leu21_Ala22insLeuLeuCysAlaLeuLeu) duplication Pathogenic rs886037749 GRCh37 Chromosome 18, 59992630: 59992647
4 TNFRSF11A NM_003839.3(TNFRSF11A): c.45_62dup18 (p.Leu21_Ala22insLeuLeuCysAlaLeuLeu) duplication Pathogenic rs886037749 GRCh38 Chromosome 18, 62325397: 62325414

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 KEGG:

37
# Name Kegg Source Accession
1 NF-kappa B signaling pathway hsa04064
2 Osteoclast differentiation hsa04380

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

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.81 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
2
Show member pathways
12.45 TNFRSF11A TNFRSF11B TNFSF11
3
Show member pathways
12.22 TNFRSF11A TNFRSF11B TNFSF11
4
Show member pathways
12.06 TNFRSF11A TNFSF11
5
Show member pathways
11.85 SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
6 11.8 TNFRSF11A TNFSF11
7 11.47 TNFRSF11A TNFSF11
8 11.43 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 10.91 TNFRSF11B TNFSF11
13 10.51 TNFRSF11B TNFSF11
14 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 14)
# Name GO ID Score Top Affiliating Genes
1 immune response GO:0006955 9.63 TNFRSF11A TNFRSF11B TNFSF11
2 response to lipopolysaccharide GO:0032496 9.54 TNFRSF11A TNFRSF11B
3 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.52 TNFRSF11A TNFSF11
4 positive regulation of DNA binding transcription factor activity GO:0051091 9.51 TNFRSF11A TNFSF11
5 ossification GO:0001503 9.49 TNFRSF11A TNFSF11
6 apoptotic signaling pathway GO:0097190 9.48 TNFRSF11A TNFRSF11B
7 monocyte chemotaxis GO:0002548 9.43 TNFRSF11A TNFSF11
8 tumor necrosis factor-mediated signaling pathway GO:0033209 9.43 TNFRSF11A TNFRSF11B TNFSF11
9 osteoclast differentiation GO:0030316 9.4 TNFRSF11A TNFSF11
10 positive regulation of bone resorption GO:0045780 9.37 TNFRSF11A TNFSF11
11 mammary gland alveolus development GO:0060749 9.32 TNFRSF11A TNFSF11
12 TNFSF11-mediated signaling pathway GO:0071847 9.16 TNFRSF11A TNFSF11
13 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFRSF11A TNFSF11
14 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 signaling receptor activity GO:0038023 8.96 TNFRSF11A TNFRSF11B
2 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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