Familial Expansile Osteolysis disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Bone diseases

See all MalaCards categories (disease lists)

ICD10: ³⁴

Diseases of the musculoskeletal system and connective tissue

Other osteopathies

Other disorders of bone

Osteolysis

Orphanet: ⁵⁹

Rare bone diseases

Developmental anomalies during embryogenesis

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

SNOMED-CT via HPO ⁶⁹ 263681008 44057004 12584003 more

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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.

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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:

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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 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

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Drugs & Therapeutics for Familial Expansile Osteolysis

Search Clinical Trials , NIH Clinical Center for Familial Expansile Osteolysis

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Genetic Tests for Familial Expansile Osteolysis

Genetic tests related to Familial Expansile Osteolysis:

#	Genetic test	Affiliating Genes
1	Familial Expansile Osteolysis ²⁹	TNFRSF11A

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Anatomical Context for Familial Expansile Osteolysis

MalaCards organs/tissues related to Familial Expansile Osteolysis:

⁴¹

Bone, Cortex

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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 )	Topham D.G....Sampson M.J.	2016
2	Osteogenic sarcoma in a child with familial expansile osteolysis syndrome: an accidental association? ( 20168251 )	Bacri D....Postovsky S.	2010
3	Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. ( 18328984 )	Ralston S.H.	2008
4	Familial expansile osteolysis--not exclusively an adult disorder. ( 16470392 )	Marik I....Kozlowski K.	2006
5	Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis. ( 15793411 )	Daneshi A....Farhang F.	2005
6	Identification of a novel tandem duplication in exon 1 of the TNFRSF11A gene in two unrelated patients with familial expansile osteolysis. ( 12568416 )	Johnson-Pais T.L....Leach R.J.	2003
7	Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred. ( 11889411 )	Whyte M.P....Mills B.G.	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 )	Whyte M.P....Hughes A.E.	2002
9	Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene. ( 12362049 )	Palenzuela L....Andreu A.L.	2002
10	Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. ( 10615125 )	Hughes A.E....Anderson D.M.	2000
11	Conductive hearing loss caused by hereditary incus necrosis: a study of familial expansile osteolysis. ( 8643278 )	Esselman G.H....Wippold F.J.	1996
12	Genetic linkage of familial expansile osteolysis to chromosome 18q. ( 7911698 )	Hughes A.E....Mollan R.A.	1994
13	Familial expansile osteolysis: a morphological, histomorphometric and serological study. ( 1664226 )	Dickson G.R....Mollan R.A.	1991
14	Dental abnormalities associated with familial expansile osteolysis: a clinical and radiographic study. ( 2216357 )	Mitchell C.A....Wallace R.G.	1990
15	Dental histology in familial expansile osteolysis. ( 2341974 )	Mitchell C.A....Owens P.D.	1990
16	The radiographic features of familial expansile osteolysis. ( 2353208 )	Crone M.D....Wallace R.G.	1990
17	Familial expansile osteolysis. ( 2530018 )	Wallace R.G....Mollan R.A.	1989
18	Familial expansile osteolysis. A new dysplasia. ( 3346299 )	Osterberg P.H....Toner P.G.	1988

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Genes for Familial Expansile Osteolysis

Genes related to Familial Expansile Osteolysis (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	TNFRSF11A	TNF Receptor Superfamily Member 11a	Protein Coding	1410.12	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation ⁵⁹ Genetic Tests ²⁹ Novoseek inferred ⁵⁵ GeneCards inferred via : Disorders Publications Summaries Variants (show sections)	10615125 7911698 12362049 (more) 17447113 12568416 17284635 11555792 11771666 11973628 12568416 16104845 17174136 18328984 16831914 10615125 11165949 17229006
2	TNFRSF11B	TNF Receptor Superfamily Member 11b	Protein Coding	20.01	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	17284635 17174136
3	SQSTM1	Sequestosome 1	Protein Coding	19.35	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	17284635
4	TNFSF11	TNF Superfamily Member 11	Protein Coding	16.5	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	17174136

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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

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Expression for Familial Expansile Osteolysis

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

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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	Cytokine Signaling in Immune system ⁶⁶ Show member pathways Signaling by Interleukins ⁶⁶	12.81	SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
2	Development Angiotensin activation of ERK ²² Show member pathways Cell adhesion Integrin inside-out signaling ²² Development ACM2 and ACM4 activation of ERK ²² Development Angiotensin signaling via PYK2 ²² Development EDNRB signaling ²² Development EPO-induced MAPK pathway ²² Development G-Proteins mediated regulation MARK-ERK signaling ²² Signal transduction IP3 signaling ²²	12.45	TNFRSF11A TNFRSF11B TNFSF11
3	Development Endothelin-1/EDNRA signaling ²² Show member pathways Cytoskeleton remodeling FAK signaling ²² Development Endothelin-1/EDNRA transactivation of EGFR ²² GnRH signaling pathway ³⁷ Inflammatory mediator regulation of TRP channels ³⁷	12.22	TNFRSF11A TNFRSF11B TNFSF11
4	TRAF Pathway ⁶⁴ Show member pathways 14-3-3 Induced Apoptosis ⁶⁴ TNF Superfamily Pathway ⁶⁴ Toll-Like Receptors Pathway ⁶⁴	12.06	TNFRSF11A TNFSF11
5	RANK Signaling in Osteoclasts ⁶⁴ Show member pathways Apoptosis and survival APRIL and BAFF signaling ²² APRIL Pathway ⁶⁴ BAFF in B-Cell Signaling ⁶⁴ RANK Pathway ⁶⁴ RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway ¹	11.85	SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
6	Apoptosis and Autophagy ⁴	11.8	TNFRSF11A TNFSF11
7	NF-kappa B signaling pathway ³⁷	11.47	TNFRSF11A TNFSF11
8	Rheumatoid arthritis ³⁷	11.43	TNFRSF11A TNFSF11
9	Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway ²² Show member pathways Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway ²²	11.36	SQSTM1 TNFRSF11A TNFSF11
10	Transcription_Role of VDR in regulation of genes involved in osteoporosis ²²	11.09	TNFRSF11A TNFRSF11B TNFSF11
11	Osteoclast differentiation ³⁷	11.03	SQSTM1 TNFRSF11A TNFRSF11B TNFSF11
12	TNFs bind their physiological receptors ⁶⁶	10.91	TNFRSF11B TNFSF11
13	Osteoblast Signaling ¹	10.51	TNFRSF11B TNFSF11
14	Osteoclast Signaling ¹	10.34	TNFRSF11A TNFRSF11B TNFSF11

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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

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