FEO
MCID: FML345
MIFTS: 46

Familial Expansile Osteolysis (FEO)

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

Aliases & Classifications for Familial Expansile Osteolysis

MalaCards integrated aliases for Familial Expansile Osteolysis:

Name: Familial Expansile Osteolysis 57 12 20 58 73 36 29 54 6 15
Osteolysis, Familial Expansile 57 20 13 39
Mccabe Disease 57 12 20 58
Feo 57 12 20 73
Polyostotic Osteolytic Dysplasia, Hereditary Expansile 57 20 44
Hereditary Expansile Polyostotic Osteolytic Dysplasia 12 58
Expansile Osteolysis, Familial 57 20
Hepod 57 20
Eof 57 20
Polyostotic Osteolytic Dysplasia, Hereditary Expansile; Hepod 57
Expansile Osteolysis, Familial; Eof 57

Characteristics:

Orphanet epidemiological data:

58
familial expansile osteolysis
Inheritance: Autosomal dominant;

OMIM®:

57 (Updated 05-Mar-2021)
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® 57 174810
KEGG 36 H02042
MeSH 44 C536335
SNOMED-CT 67 254153009
MESH via Orphanet 45 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

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 85195DefinitionA 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 conductive hearing impairment

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® : 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) (Updated 05-Mar-2021)

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 61)
# Related Disease Score Top Affiliating Genes
1 mammary paget's disease 31.0 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
2 paget disease of bone 2, early-onset 30.8 TNFRSF11A SQSTM1
3 paget's disease of bone 30.8 TNFSF11 TNFRSF11B TNFRSF11A SQSTM1
4 root resorption 30.6 TNFSF11 TNFRSF11B TNFRSF11A SPP1
5 fibrous dysplasia 30.4 TNFSF11 TNFRSF11A SPP1
6 osteopetrosis 30.2 TNFSF11 TNFRSF11B TNFRSF11A
7 branchiootic syndrome 1 10.4
8 periodontitis, chronic 10.3 TNFSF11 TNFRSF11B
9 gastric cancer 10.3
10 breast leiomyosarcoma 10.3 TNFSF11 MB
11 multicentric reticulohistiocytosis 10.3 TNFSF11 TNFRSF11B
12 polyarticular onset juvenile idiopathic arthritis 10.3 TNFSF11 TNFRSF11B TNFRSF11A
13 hemophilic arthropathy 10.3 TNFSF11 TNFRSF11B TNFRSF11A
14 arthropathy 10.3 TNFSF11 TNFRSF11B TNFRSF11A
15 disseminated chorioretinitis 10.3 TNFSF11 TNFRSF11B TNFRSF11A
16 paget disease of bone 5, juvenile-onset 10.3 TNFSF11 TNFRSF11B TNFRSF11A
17 periostitis 10.3 TNFRSF11B TNFRSF11A SQSTM1
18 chronic apical periodontitis 10.3 TNFSF11 TNFRSF11B
19 multicentric carpotarsal osteolysis syndrome 10.3 TNFSF11 TNFRSF11B TNFRSF11A
20 aneurysmal bone cysts 10.3 TNFSF11 TNFRSF11A
21 benign giant cell tumor 10.3 TNFSF11 TNFRSF11B TNFRSF11A
22 tooth resorption 10.2 TNFSF11 TNFRSF11A SPP1
23 ischemic bone disease 10.2 TNFSF11 TNFRSF11A SPP1
24 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
25 gingival recession 10.2 TNFSF11 C1S
26 myasthenic syndrome, congenital, 18 10.2 SERF1B SERF1A
27 giant cell reparative granuloma 10.2 TNFSF11 TNFRSF11A
28 locked-in syndrome 10.2 SERF1B SERF1A
29 bone resorption disease 10.2 TNFSF11 TNFRSF11B TNFRSF11A SPP1
30 bone remodeling disease 10.2 TNFSF11 TNFRSF11B TNFRSF11A SPP1
31 form agnosia 10.1 SERF1B SERF1A
32 bone disease 10.1 TNFSF11 TNFRSF11B TNFRSF11A SPP1
33 brittle bone disorder 10.1 TNFSF11 TNFRSF11B TNFRSF11A SPP1
34 rapidly involuting congenital hemangioma 10.1
35 osteopetrosis, autosomal recessive 7 10.1 TNFSF11 TNFRSF11A
36 interstitial nephritis, karyomegalic 10.1 VASP NDUFAF3 AP4M1
37 osteogenic sarcoma 10.1
38 pycnodysostosis 10.1
39 frontotemporal dementia 10.1
40 osteofibrous dysplasia 10.1
41 sarcoma 10.1
42 myopathy 10.1
43 spindle cell sarcoma 10.1
44 gorham's disease 10.1
45 lactase deficiency, congenital 10.1 NOC2L MIOX MB
46 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 10.1 SERF1B SERF1A NDUFAF3 C1S
47 triiodothyronine receptor auxiliary protein 10.0
48 plague 10.0
49 familial febrile seizures 10.0 VASP NOC2L MB
50 neutropenia 9.9

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 conductive hearing impairment 31 HP:0000405
3 bone pain 31 HP:0002653
4 osteolysis 31 HP:0002797
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®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

GenomeRNAi Phenotypes related to Familial Expansile Osteolysis according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.58 TNFRSF11B
2 Decreased viability GR00221-A-2 9.58 TNFRSF11B
3 Decreased viability GR00231-A 9.58 SQSTM1
4 Decreased viability GR00240-S-1 9.58 MIOX TNFRSF11A
5 Decreased viability GR00249-S 9.58 NOC2L SPP1 TNFRSF11B
6 Decreased viability GR00381-A-1 9.58 SERF1B SQSTM1
7 Decreased viability GR00386-A-1 9.58 AP4M1 MB MIOX TNFSF11
8 Decreased viability GR00402-S-2 9.58 MIOX SQSTM1 TNFRSF11B TNFSF11

MGI Mouse Phenotypes related to Familial Expansile Osteolysis:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.07 AP4M1 DOHH FBXL5 KDM4C MB MIOX
2 hematopoietic system MP:0005397 9.97 AP4M1 DOHH FBXL5 KDM4C MB NOC2L
3 homeostasis/metabolism MP:0005376 9.77 AP4M1 DOHH FBXL5 KDM4C MB MIOX
4 immune system MP:0005387 9.36 DOHH FBXL5 KDM4C NOC2L RAB6B SERF1B

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 57 54
12568416 2003
2
Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. 57 6 54 61
10615125 2000
3
Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation. 57 6 61
17447113 2007
4
Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene. 61 57 6
12362049 2002
5
Genetic linkage of familial expansile osteolysis to chromosome 18q. 61 57 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. 57 54 61
11771666 2002
7
Panostotic expansile bone disease with massive jaw tumor formation and a novel mutation in the signal peptide of RANK. 57 61
24014458 2014
8
Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis. 61 57
15793411 2005
9
Familial expansile osteolysis: a morphological, histomorphometric and serological study. 57 61
1664226 1991
10
Familial expansile osteolysis. 61 57
2530018 1989
11
Familial expansile osteolysis. A new dysplasia. 61 57
3346299 1988
12
Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease. 57
11127198 2000
13
Idiopathic multicentric osteolysis: report of two new cases and a review of the literature. 57
2774005 1989
14
Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. 61 54
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. 61 54
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. 61 54
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. 61 54
11555792 2001
22
Evaluation of the role of RANK and OPG genes in Paget's disease of bone. 61 54
11165949 2001
23
Genetic disorders associated with the RANKL/OPG/RANK pathway. 61
32940787 2021
24
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
25
Multiple External Root Resorption in a Pediatric Patient with Familial Expansile Osteolysis. 61
32075714 2020
26
Rare Inherited forms of Paget's Disease and Related Syndromes. 61
30756140 2019
27
Dysosteosclerosis is also caused by TNFRSF11A mutation. 61
29568001 2018
28
Familial expansile osteolysis: An Australian case report of a Paget's Disease Mimic. 61
27258166 2016
29
Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding RANK. 61
25063546 2014
30
Signal peptide mutations in RANK prevent downstream activation of NF-κB. 61
21472776 2011
31
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
32
Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone. 61
20564239 2010
33
[Cytokines in bone diseases. Genetic disorders of RANKL-RANK-OPG system]. 61
20890036 2010
34
Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association? 61
20168251 2010
35
Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy. 61
18836673 2008
36
Genetics and aetiology of Pagetic disorders of bone. 61
18359282 2008
37
Pathophysiology and genetics of metabolic bone disorders characterized by increased bone turnover. 61
17725490 2007
38
A newly recognized polyosteolysis/hyperostosis syndrome. 61
17001672 2006
39
Familial expansile osteolysis--not exclusively an adult disorder. 61
16470392 2006
40
Mechanisms of disease: genetics of Paget's disease of bone and related disorders. 61
16932700 2006
41
Metabolic bone disease in children : etiology and treatment options. 61
17002489 2006
42
Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. 61
12929927 2003
43
Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred. 61
11889411 2002
44
Linkage of Paget disease of bone to a novel region on human chromosome 18q23. 61
11742440 2002
45
Minireview: the OPG/RANKL/RANK system. 61
11713196 2001
46
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
47
Familial Paget's disease of bone: patterns of inheritance and frequency of linkage to chromosome 18q. 61
10831928 2000
48
Variable disease severity associated with a Paget's disease predisposition gene. 61
10510208 1999
49
Common mechanisms of osteosarcoma and Paget's disease. 61
10510212 1999
50
Tooth root resorption associated with a familial bone dysplasia affecting mother and daughter. 61
10509339 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.45_62dup (p.Leu16_Leu21dup) Duplication Pathogenic 208143 rs886037749 18:59992620-59992621 18:62325387-62325388
4 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
12.07 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 10.55 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 cytosol GO:0005829 9.4 VASP TNFRSF11A SQSTM1 SERF1B SERF1A RAB6B
2 inclusion body GO:0016234 8.96 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 9.61 TNFSF11 TNFRSF11B TNFRSF11A
2 ossification GO:0001503 9.54 TNFSF11 TNFRSF11A SPP1
3 mammary gland alveolus development GO:0060749 9.4 TNFSF11 TNFRSF11A
4 amyloid fibril formation GO:1990000 9.32 SERF1B SERF1A
5 TNFSF11-mediated signaling pathway GO:0071847 9.26 TNFSF11 TNFRSF11A
6 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 9.16 TNFSF11 TNFRSF11A
7 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFSF11 TNFRSF11A
8 positive regulation of bone resorption GO:0045780 8.8 TNFSF11 TNFRSF11A SPP1

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

# Name GO ID Score Top Affiliating Genes
1 iron ion binding GO:0005506 8.8 MIOX FBXL5 DOHH

Sources for Familial Expansile Osteolysis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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