FEO
MCID: FML345
MIFTS: 43

Familial Expansile Osteolysis (FEO)

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

Aliases & Classifications for Familial Expansile Osteolysis

MalaCards integrated aliases for Familial Expansile Osteolysis:

Name: Familial Expansile Osteolysis 56 12 52 58 73 36 29 54 6 15
Osteolysis, Familial Expansile 56 52 13 39
Mccabe Disease 56 12 52 58
Feo 56 12 52 73
Polyostotic Osteolytic Dysplasia, Hereditary Expansile 56 52 43
Hereditary Expansile Polyostotic Osteolytic Dysplasia 12 58
Expansile Osteolysis, Familial 56 52
Hepod 56 52
Eof 56 52
Polyostotic Osteolytic Dysplasia, Hereditary Expansile; Hepod 56
Expansile Osteolysis, Familial; Eof 56

Characteristics:

Orphanet epidemiological data:

58
familial expansile osteolysis
Inheritance: Autosomal dominant;

OMIM:

56
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:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111542
OMIM 56 174810
KEGG 36 H02042
MeSH 43 C536335
SNOMED-CT 67 254153009
MESH via Orphanet 44 C536335
ICD10 via Orphanet 33 M89.5
UMLS via Orphanet 72 C0432292
Orphanet 58 ORPHA85195
MedGen 41 C0432292
UMLS 71 C0432292

Summaries for Familial Expansile Osteolysis

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85195 Definition A rare primary bone dysplasia characterized by abnormal bone metabolism with bone pain, deformity, pathological fractures, early conductive hearing loss , and dental abnormalities. Focal bone lesions are typically found in the appendicular skeleton and consist of progressively expanding lytic areas, while generalized disordered bone modeling and altered trabecular pattern are the result of the multifocal, progressive nature of the disease. Age of onset is variable, mode of inheritance is autosomal dominant . Visit the Orphanet disease page for more resources.

MalaCards based summary : Familial Expansile Osteolysis, also known as osteolysis, familial expansile, is related to mammary paget's disease and paget disease of bone 2, early-onset. 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 osteolysis

Disease Ontology : 12 A bone remodeling disease characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton, bone pain, pathological fractures, childhood onset of conductive hearing loss, and premature tooth loss that has material basis in heterozygous mutation in TNFRSF11A on chromosome 18q21.33.

OMIM : 56 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)

KEGG : 36 Familial expansile osteolysis (FEO) is a rare autosomal dominant disorder causing bone dysplasia. It is characterized by increased osteoclast activity, medullary expansion, and hearing and dental problems. The mutations in the TNFRSF11A gene encoding RANK have been identified. FEO is similar in some respects to Paget's disease but distinct enough in its clinical, radiological and histological findings to be classified as a separate disease.

UniProtKB/Swiss-Prot : 73 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 top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 mammary paget's disease 31.3 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
2 paget disease of bone 2, early-onset 31.1 TNFRSF11A SQSTM1
3 paget's disease of bone 31.0 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
4 root resorption 30.8 TNFSF11 TNFRSF11B TNFRSF11A SPP1
5 fibrous dysplasia 30.5 TNFSF11 TNFRSF11B TNFRSF11A SPP1
6 osteopetrosis 30.4 TNFSF11 TNFRSF11B TNFRSF11A
7 gastric cancer 10.6
8 polyarticular onset juvenile idiopathic arthritis 10.5 TNFSF11 TNFRSF11B TNFRSF11A
9 periodontitis, chronic 10.5 TNFSF11 TNFRSF11B
10 hemophilic arthropathy 10.5 TNFSF11 TNFRSF11B TNFRSF11A
11 arthropathy 10.5 TNFSF11 TNFRSF11B TNFRSF11A
12 paget disease of bone 5, juvenile-onset 10.5 TNFSF11 TNFRSF11B TNFRSF11A
13 disseminated chorioretinitis 10.5 TNFSF11 TNFRSF11B TNFRSF11A
14 periostitis 10.4 TNFRSF11B TNFRSF11A SQSTM1
15 multicentric carpotarsal osteolysis syndrome 10.4 TNFSF11 TNFRSF11B TNFRSF11A
16 multicentric reticulohistiocytosis 10.4 TNFSF11 TNFRSF11B
17 branchiootic syndrome 1 10.4
18 benign giant cell tumor 10.4 TNFSF11 TNFRSF11B TNFRSF11A
19 aneurysmal bone cysts 10.4 TNFSF11 TNFRSF11A
20 breast leiomyosarcoma 10.4 TNFSF11 MB
21 chronic apical periodontitis 10.4 TNFSF11 TNFRSF11B SNRNP40
22 rapidly involuting congenital hemangioma 10.4
23 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.3
24 periodontitis 10.3 TNFSF11 TNFRSF11B SPP1
25 endosteal hyperostosis, autosomal dominant 10.3 TNFSF11 TNFRSF11B SQSTM1
26 parathyroid gland disease 10.3 TNFSF11 TNFRSF11B KDM4C
27 ischemic bone disease 10.3 TNFSF11 TNFRSF11B SPP1
28 osseous heteroplasia, progressive 10.3 MT-CO3 GRIK1 C1S
29 gaucher disease, type iii 10.3 MT-CO3 GRIK1 APEX2
30 mineral metabolism disease 10.3 TNFSF11 TNFRSF11B SPP1
31 failure of tooth eruption, primary 10.3 TNFRSF11A SPAG17 PRDM10
32 triiodothyronine receptor auxiliary protein 10.3
33 plague 10.3
34 hypercholesterolemia, familial, 4 10.3 SPAG17 GRIK1 APEX2
35 neutropenia 10.3
36 tooth resorption 10.3 TNFSF11 TNFRSF11B TNFRSF11A SPP1
37 bone giant cell tumor 10.3 TNFSF11 TNFRSF11B TNFRSF11A SPP1
38 dental pulp necrosis 10.2 TNFSF11 SNRNP40
39 kummell's disease 10.2 TNFSF11 TNFRSF11B
40 teeth hard tissue disease 10.2 TNFSF11 TNFRSF11B PRDM10
41 bone resorption disease 10.2 TNFSF11 TNFRSF11B TNFRSF11A SPP1
42 bone remodeling disease 10.2 TNFSF11 TNFRSF11B TNFRSF11A SPP1
43 bone cancer 10.2 TNFSF11 TNFRSF11B TNFRSF11A KDM4C
44 bone disease 10.2 TNFSF11 TNFRSF11B TNFRSF11A SPP1
45 brittle bone disorder 10.2 TNFSF11 TNFRSF11B SPP1
46 giant cell reparative granuloma 10.2 TNFSF11 TNFRSF11A
47 hyperpigmentation with or without hypopigmentation, familial progressive 10.1 SPP1 SPAG17 GSTM1
48 aortic valve disease 2 10.1 TNFSF11 TNFRSF11B SPP1
49 interstitial nephritis, karyomegalic 10.1 TUBA1B SNRNP40 NDUFAF3 C1S
50 autosomal recessive cerebellar ataxia 10.1

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



Diseases related to Familial Expansile Osteolysis

Symptoms & Phenotypes for Familial Expansile Osteolysis

Human phenotypes related to Familial Expansile Osteolysis:

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

Symptoms via clinical synopsis from OMIM:

56
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

MGI Mouse Phenotypes related to Familial Expansile Osteolysis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.44 APEX2 DOHH GRIK1 KDM4C MB MIOX

Drugs & Therapeutics for Familial Expansile Osteolysis

Search Clinical Trials , NIH Clinical Center for Familial Expansile Osteolysis

Cochrane evidence based reviews: polyostotic osteolytic dysplasia, hereditary expansile

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:

40
Bone, Cortex

Publications for Familial Expansile Osteolysis

Articles related to Familial Expansile Osteolysis:

(show top 50) (show all 56)
# Title Authors PMID Year
1
Identification of a novel tandem duplication in exon 1 of the TNFRSF11A gene in two unrelated patients with familial expansile osteolysis. 6 61 56 54
12568416 2003
2
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. 56 6 61 54
10615125 2000
3
Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation. 56 61 6
17447113 2007
4
Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene. 61 56 6
12362049 2002
5
Genetic linkage of familial expansile osteolysis to chromosome 18q. 61 56 6
7911698 1994
6
Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. 61 54 56
11771666 2002
7
Panostotic expansile bone disease with massive jaw tumor formation and a novel mutation in the signal peptide of RANK. 61 56
24014458 2014
8
Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis. 56 61
15793411 2005
9
Familial expansile osteolysis: a morphological, histomorphometric and serological study. 56 61
1664226 1991
10
Familial expansile osteolysis. 61 56
2530018 1989
11
Familial expansile osteolysis. A new dysplasia. 61 56
3346299 1988
12
Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease. 56
11127198 2000
13
Idiopathic multicentric osteolysis: report of two new cases and a review of the literature. 56
2774005 1989
14
Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. 54 61
18328984 2008
15
Sporadic hyperphosphatasia syndrome featuring periostitis and accelerated skeletal turnover without receptor activator of nuclear factor-kappaB, osteoprotegerin, or sequestosome-1 gene defects. 54 61
17284635 2007
16
RANK ligand. 54 61
17174136 2007
17
Contribution of genetic factors to the pathogenesis of Paget's disease of bone and related disorders. 54 61
17229006 2006
18
Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling. 54 61
16831914 2006
19
Genetics of Paget's disease of bone. 54 61
16104845 2005
20
Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3-18q22. 54 61
11973628 2002
21
Genomewide search in familial Paget disease of bone shows evidence of genetic heterogeneity with candidate loci on chromosomes 2q36, 10p13, and 5q35. 54 61
11555792 2001
22
Evaluation of the role of RANK and OPG genes in Paget's disease of bone. 61 54
11165949 2001
23
Early-onset Paget's disease of bone in a Mexican family caused by a novel tandem duplication (77dup27) in TNFRSF11A that encodes RANK. 61
31923705 2020
24
Multiple External Root Resorption in a Pediatric Patient with Familial Expansile Osteolysis. 61
32075714 2020
25
Rare Inherited forms of Paget's Disease and Related Syndromes. 61
30756140 2019
26
Dysosteosclerosis is also caused by TNFRSF11A mutation. 61
29568001 2018
27
Familial expansile osteolysis: An Australian case report of a Paget's Disease Mimic. 61
27258166 2016
28
Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding RANK. 61
25063546 2014
29
Signal peptide mutations in RANK prevent downstream activation of NF-κB. 61
21472776 2011
30
New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. 61
20458572 2011
31
Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone. 61
20564239 2010
32
[Cytokines in bone diseases. Genetic disorders of RANKL-RANK-OPG system]. 61
20890036 2010
33
Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association? 61
20168251 2010
34
Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy. 61
18836673 2008
35
Genetics and aetiology of Pagetic disorders of bone. 61
18359282 2008
36
Pathophysiology and genetics of metabolic bone disorders characterized by increased bone turnover. 61
17725490 2007
37
A newly recognized polyosteolysis/hyperostosis syndrome. 61
17001672 2006
38
Familial expansile osteolysis--not exclusively an adult disorder. 61
16470392 2006
39
Mechanisms of disease: genetics of Paget's disease of bone and related disorders. 61
16932700 2006
40
Metabolic bone disease in children : etiology and treatment options. 61
17002489 2006
41
Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. 61
12929927 2003
42
Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred. 61
11889411 2002
43
Linkage of Paget disease of bone to a novel region on human chromosome 18q23. 61
11742440 2002
44
Minireview: the OPG/RANKL/RANK system. 61
11713196 2001
45
Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. 61
11351498 2001
46
Familial Paget's disease of bone: patterns of inheritance and frequency of linkage to chromosome 18q. 61
10831928 2000
47
Variable disease severity associated with a Paget's disease predisposition gene. 61
10510208 1999
48
Common mechanisms of osteosarcoma and Paget's disease. 61
10510212 1999
49
Tooth root resorption associated with a familial bone dysplasia affecting mother and daughter. 61
10509339 1999
50
Expansile bone lesions in a three-generation family. 61
9916834 1999

Variations for Familial Expansile Osteolysis

ClinVar genetic disease variations for Familial Expansile Osteolysis:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TNFRSF11A NM_003839.4(TNFRSF11A):c.46_63dup (p.Leu16_Leu21dup)duplication Pathogenic 6299 rs879253796 18:59992630-59992631 18:62325397-62325398
2 TNFRSF11A NM_003839.4(TNFRSF11A):c.45_62dup (p.Leu16_Leu21dup)duplication Pathogenic 208143 rs886037749 18:59992620-59992621 18:62325387-62325388
3 TNFRSF11A NM_003839.4(TNFRSF11A):c.718A>G (p.Lys240Glu)SNV Uncertain significance 287370 rs148185533 18:60029014-60029014 18:62361781-62361781

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:

36
# 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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.1 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
2 11.56 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
3
Show member pathways
11.41 TNFSF11 TNFRSF11B TNFRSF11A
4
Show member pathways
11.3 TNFSF11 TNFRSF11A SQSTM1
5 10.91 TNFSF11 TNFRSF11B TNFRSF11A SPP1
6 10.51 TNFSF11 TNFRSF11B
7 10.13 TNFSF11 TNFRSF11B TNFRSF11A SPP1

GO Terms for Familial Expansile Osteolysis

Cellular components related to Familial Expansile Osteolysis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 inclusion body GO:0016234 8.62 SQSTM1 MIOX

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

# Name GO ID Score Top Affiliating Genes
1 tumor necrosis factor-mediated signaling pathway GO:0033209 9.58 TNFSF11 TNFRSF11B TNFRSF11A
2 ossification GO:0001503 9.5 TNFSF11 TNFRSF11A SPP1
3 mammary gland alveolus development GO:0060749 9.37 TNFSF11 TNFRSF11A
4 TNFSF11-mediated signaling pathway GO:0071847 9.26 TNFSF11 TNFRSF11A
5 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 9.16 TNFSF11 TNFRSF11A
6 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFSF11 TNFRSF11A
7 positive regulation of bone resorption GO:0045780 8.8 TNFSF11 TNFRSF11A SPP1

Sources for Familial Expansile Osteolysis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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