MCID: MTP001
MIFTS: 39

Metaphyseal Dysplasia

Categories: Bone diseases, Fetal diseases, Rare diseases
Data Licensing
For inquiries, contact:

Aliases & Classifications for Metaphyseal Dysplasia

MalaCards integrated aliases for Metaphyseal Dysplasia:

Name: Metaphyseal Dysplasia 11 53 5 14 75 31
Bakwin-Krida Syndrome 11
Pyle-Cohn Syndrome 11
Pyle's Disease 11

Classifications:



External Ids:

Disease Ontology 11 DOID:0080019
ICD10 31 Q78.5

Summaries for Metaphyseal Dysplasia

Disease Ontology: 11 An osteochondrodysplasia that is characterized by abnormally broad ends of the arm and leg long bones resembling a boat oar or paddle due to enlargement of the spongy inner layer of bone.

MalaCards based summary: Metaphyseal Dysplasia, also known as bakwin-krida syndrome, is related to intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies and cartilage-hair hypoplasia. An important gene associated with Metaphyseal Dysplasia is SFRP4 (Secreted Frizzled Related Protein 4), and among its related pathways/superpathways are Mesenchymal Stem Cells and Lineage-specific Markers and Endochondral ossification. Affiliated tissues include bone, neutrophil and thymus, and related phenotypes are growth/size/body region and homeostasis/metabolism

Wikipedia: 75 Metaphyseal dysplasia, or Pyle disease, is a disorder of the bones. It is a rare disease in which the... more...

Related Diseases for Metaphyseal Dysplasia

Diseases in the Metaphyseal Dysplasia family:

Multiple Metaphyseal Dysplasia

Diseases related to Metaphyseal Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 245)
# Related Disease Score Top Affiliating Genes
1 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 33.1 POLE NR0B1 CDKN1C
2 cartilage-hair hypoplasia 31.9 SBDS RMRP COL10A1
3 anauxetic dysplasia 1 31.8 SBDS RMRP EFL1
4 metaphyseal chondrodysplasia, jansen type 31.7 PTHLH PTH1R PTH
5 osteopetrosis 30.7 RUNX2 LRRK1 ACP5
6 coxa vara 30.6 MMP13 COL2A1 COL10A1
7 endosteal hyperostosis, autosomal dominant 30.5 SFRP4 PTH ACP5
8 brachydactyly 30.4 RUNX2 PTHLH PTH COL2A1
9 cartilage disease 30.3 RUNX2 MMP13 COL2A1 COL10A1
10 spondyloepimetaphyseal dysplasia, strudwick type 30.2 PTH1R COL2A1 COL10A1
11 scoliosis 30.1 RUNX2 MMP13 COL2A1 COL10A1 CDKN1C ACP5
12 spondylometaphyseal dysplasia, corner fracture type 30.0 EFL1 COL2A1
13 hypophosphatasia 30.0 SFRP4 RUNX2 PTH
14 osteochondrosis 30.0 PTH MMP13 COL2A1
15 metatropic dysplasia 30.0 RUNX2 COL2A1
16 spondyloepimetaphyseal dysplasia 30.0 RMRP MMP13 DYM COL2A1
17 craniosynostosis 30.0 RUNX2 EXTL3 COL2A1 CDKN1C
18 osteoarthritis 29.9 RUNX2 MMP13 COL2A1 COL10A1
19 chondrosarcoma 29.9 RUNX2 PTHLH MMP13 COL10A1
20 cleidocranial dysplasia 1 29.8 RUNX2 PTHLH PTH1R NKX3-2 MMP13 COL2A1
21 exostosis 29.8 RUNX2 PTHLH MMP13 EXTL3 COL2A1
22 bone disease 29.7 RUNX2 PTHLH PTH1R PTH MMP13 COL2A1
23 primary hyperparathyroidism 29.7 PTHLH PTH1R PTH ACP5
24 hyperparathyroidism 29.7 PTHLH PTH1R PTH ACP5
25 osteonecrosis 29.6 RUNX2 PTH1R PTH COL2A1 ACP5
26 enchondromatosis, multiple, ollier type 29.2 RUNX2 PTHLH PTH1R PTH MMP13 COL2A1
27 osteochondrodysplasia 29.1 SFRP4 SBDS RUNX2 RMRP PTHLH PTH1R
28 metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 11.8
29 pyle disease 11.8
30 spondylo-megaepiphyseal-metaphyseal dysplasia 11.7
31 osteosclerotic metaphyseal dysplasia 11.6
32 metaphyseal dysplasia without hypotrichosis 11.6
33 ulna metaphyseal dysplasia syndrome 11.6
34 microspherophakia-metaphyseal dysplasia 11.6
35 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 11.6
36 metaphyseal anadysplasia 11.6
37 metaphyseal dysplasia, spahr type 11.6
38 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 11.5
39 metaphyseal dysplasia, braun-tinschert type 11.5
40 metaphyseal chondrodysplasia, schmid type 11.4
41 shwachman-diamond syndrome 1 11.4
42 spondylometaphyseal dysplasia, algerian type 11.3
43 spondyloepimetaphyseal dysplasia, micromelic 11.2
44 metaphyseal dysplasia, anetoderma, and optic atrophy 11.2
45 metaphyseal acroscyphodysplasia 11.2
46 metaphyseal dysostosis-intellectual disability-conductive deafness syndrome 11.2
47 dyggve-melchior-clausen disease 11.1
48 metaphyseal chondrodysplasia, kaitila type 11.1
49 spondylometaphyseal dysplasia, axial 11.1
50 smith-mccort dysplasia 1 11.1

Graphical network of the top 20 diseases related to Metaphyseal Dysplasia:



Diseases related to Metaphyseal Dysplasia

Symptoms & Phenotypes for Metaphyseal Dysplasia

GenomeRNAi Phenotypes related to Metaphyseal Dysplasia according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 9.88 ACP5 AIRE CDKN1C COL10A1 COL2A1 DYM
2 no effect GR00402-S-2 9.88 ACP5 AIRE CDKN1C COL2A1 DYM EFL1

MGI Mouse Phenotypes related to Metaphyseal Dysplasia:

45 (show all 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.37 AIRE CDKN1C COL10A1 COL2A1 DYM EXTL3
2 homeostasis/metabolism MP:0005376 10.36 AIRE CDKN1C COL2A1 DYM EXTL3 LRRK1
3 limbs/digits/tail MP:0005371 10.34 ACP5 CDKN1C COL10A1 COL2A1 DYM LRRK1
4 endocrine/exocrine gland MP:0005379 10.29 AIRE CDKN1C COL10A1 DYM EXTL3 NKX3-2
5 immune system MP:0005387 10.24 ACP5 AIRE CDKN1C COL10A1 COL2A1 EXTL3
6 cellular MP:0005384 10.18 CDKN1C COL10A1 COL2A1 DYM EXTL3 MMP13
7 craniofacial MP:0005382 10.13 CDKN1C COL10A1 COL2A1 DYM LRRK1 NKX3-2
8 skeleton MP:0005390 10.13 ACP5 CDKN1C COL10A1 COL2A1 DYM LRRK1
9 digestive/alimentary MP:0005381 10.11 AIRE CDKN1C COL2A1 NKX3-2 PTH1R PTHLH
10 liver/biliary system MP:0005370 10.08 AIRE COL2A1 EXTL3 PTH1R PTHLH RUNX2
11 respiratory system MP:0005388 9.92 AIRE CDKN1C COL2A1 NKX3-2 PTH1R PTHLH
12 hematopoietic system MP:0005397 9.86 ACP5 AIRE CDKN1C COL10A1 DYM EXTL3
13 vision/eye MP:0005391 9.81 AIRE CDKN1C COL2A1 EXTL3 LRRK1 PTH
14 mortality/aging MP:0010768 9.55 AIRE CDKN1C COL10A1 COL2A1 DYM EFL1

Drugs & Therapeutics for Metaphyseal Dysplasia

Search Clinical Trials, NIH Clinical Center for Metaphyseal Dysplasia

Genetic Tests for Metaphyseal Dysplasia

Anatomical Context for Metaphyseal Dysplasia

Organs/tissues related to Metaphyseal Dysplasia:

MalaCards : Bone, Neutrophil, Thymus, Placenta, Eye, Skin

Publications for Metaphyseal Dysplasia

Articles related to Metaphyseal Dysplasia:

(show top 50) (show all 343)
# Title Authors PMID Year
1
Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. 62 5
27355534 2016
2
The First Report of Biallelic Missense Mutations in the SFRP4 Gene Causing Pyle Disease in Two Siblings. 5
33193738 2020
3
Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum. 53 62
17701897 2007
4
COL2A1-related skeletal dysplasias with predominant metaphyseal involvement. 53 62
17163530 2007
5
Genetic disorders involving adrenal development. 53 62
17986825 2007
6
Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. 53 62
16252239 2005
7
Evolutionary comparison provides evidence for pathogenicity of RMRP mutations. 53 62
16244706 2005
8
Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. 53 62
14557425 2003
9
Spondylar dysplasia in type X collagenopathy. 53 62
11214689 2001
10
Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias. 53 62
7607655 1995
11
Natural history and genetic spectrum of the Turkish metaphyseal dysplasia cohort, including rare types caused by biallelic COL10A1, COL2A1, and LBR variants. 62
36400164 2022
12
Phenotypic continuum between POLE-related recessive disorders: A case report and literature review. 62
35860951 2022
13
A novel variant in GNPNAT1 gene causing a spondylo-epi-metaphyseal dysplasia resembling PGM3-Desbuquois like dysplasia. 62
36097642 2022
14
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain. 62
36040231 2022
15
Craniofacial, dental, and molecular features of Pyle disease in a South African child. 62
36138002 2022
16
Biallelic loss-of-function variants in EXOC6B are associated with impaired primary ciliogenesis and cause spondylo-epi-metaphyseal dysplasia with joint laxity type 3. 62
36150098 2022
17
Biallelic variants in the SLC13A1 sulfate transporter gene cause hyposulfatemia with a mild spondylo-epi-metaphyseal dysplasia. 62
36175384 2022
18
A missense mutation in DDRGK1 gene associated to Shohat-type spondyloepimetaphyseal dysplasia: Two case reports and a review of literature. 62
35670300 2022
19
Torticollis in Connection with Spine Phenotype. 62
35885576 2022
20
Osteosclerotic metaphyseal dysplasia, dysosteosclerosis or osteomyelitis? Paediatric case presentation with associated mandibular swelling and a review of the literature. 62
35550322 2022
21
Risk Factors for Rebound After Correction of Genu Valgum in Skeletal Dysplasia Patients Treated by Tension Band Plates. 62
35051956 2022
22
Identification of Novel Compound Heterozygous Variants of MMP9 in Fetus With Metaphyseal Anadysplasia Type 2. 62
36035187 2022
23
Exploring and expanding the phenotype and genotype diversity in seven Chinese families with spondylo-epi-metaphyseal dysplasia. 62
36118854 2022
24
Sirolimus Restores Erythropoiesis and Controls Immune Dysregulation in a Child With Cartilage-Hair Hypoplasia: A Case Report. 62
35663969 2022
25
Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity. 62
34798323 2022
26
Differential diagnosis of a diffuse sclerosis in an identified male skull (early 20th century Coimbra, Portugal): A multimethodological approach for the identification of osteosclerotic dysplasias in skeletonized individuals. 62
34243133 2021
27
Musculoskeletal imaging manifestations of beta-thalassemia. 62
33559685 2021
28
A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma. 62
34098225 2021
29
Further phenotypic features and two novel POC1A variants in a patient with SOFT syndrome: A case report. 62
33955509 2021
30
Seven patients with Smith-McCort dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings. 62
34000439 2021
31
Metaphyseal Dysplasia Without Hypotrichosis Caused by RNA Component of Mitochondrial RNA-Processing Endoribonuclease (RMRP) Gene Variants: The First Case in Korea. 62
33303724 2021
32
Early prenatal presentation of the cartilage-hair hypoplasia / anauxetic dysplasia spectrum of disorders mimicking recurrent thanatophoric dysplasia. 62
33567347 2021
33
Homozygous n.64C>T mutation in mitochondrial RNA-processing endoribonuclease gene causes cartilage hair hypoplasia syndrome in two siblings. 62
33444820 2021
34
Zebrafish model for spondylo-megaepiphyseal-metaphyseal dysplasia reveals post-embryonic roles of Nkx3.2 in the skeleton. 62
33462117 2021
35
Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature. 62
33352647 2020
36
Sedaghatian-type spondylometaphyseal dysplasia: Whole exome sequencing in neonatal dry blood spots enabled identification of a novel variant in GPX4. 62
32827718 2020
37
UFSP2-related spondyloepimetaphyseal dysplasia: A confirmatory report. 62
32755715 2020
38
Novel mutation points to a hot spot in CDKN1C causing Silver-Russell syndrome. 62
33076988 2020
39
Anesthetic management for cesarean delivery for a parturient with metaphyseal dysplasia and hypophosphatemic rickets. 62
32464576 2020
40
Wrist Joint Skeletal Changes in Children With Transfusion-dependent Thalassemia. 62
32501918 2020
41
Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation. 62
32119750 2020
42
Shortfall of exome analysis for diagnosis of Shwachman-Diamond syndrome: Mismapping due to the pseudogene SBDSP1. 62
32412173 2020
43
Spondylo-epi-metaphyseal dysplasia due to a homozygous missense mutation in the gene encoding Matrilin-3 (T120M). 62
32025536 2020
44
The novel R211Q POP1 homozygous mutation causes different pathogenesis and skeletal changes from those of previously reported POP1-associated anauxetic dysplasia. 62
32134183 2020
45
Unique Growing Rod Treatment with Prior Foundation Surgery for Spondylo-Epi-Metaphyseal Dysplasia with Severe Kyphoscoliosis: A Case Report. 62
32864499 2020
46
'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations. 62
31413121 2020
47
A novel homozygous LRRK1 stop gain mutation in a patient suspected with osteosclerotic metaphyseal dysplasia. 62
31571209 2020
48
New perspectives on the treatment of skeletal dysplasia. 62
32166011 2020
49
Pyle's Disease: A human model of differentiated cortical and trabecular homeostasis. 62
29463445 2020
50
Metaphyseal dysplasia, Spahr type: a mimicker of rickets. 62
31413057 2019

Variations for Metaphyseal Dysplasia

ClinVar genetic disease variations for Metaphyseal Dysplasia:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SFRP4 NM_003014.4(SFRP4):c.481_487del (p.Val161fs) DEL Pathogenic
242997 rs879253778 GRCh37: 7:37954014-37954020
GRCh38: 7:37914412-37914418
2 SFRP4 NM_003014.4(SFRP4):c.499dup (p.Asp167fs) DUP Pathogenic
242995 rs879255603 GRCh37: 7:37954001-37954002
GRCh38: 7:37914399-37914400
3 SFRP4 NM_003014.3(SFRP4):c.694C>T SNV Pathogenic
242996 rs755007671 GRCh37: 7:37951818-37951818
GRCh38: 7:37912216-37912216
4 SFRP4 NM_003014.4(SFRP4):c.161C>A (p.Ala54Asp) SNV Likely Pathogenic
989454 rs758308395 GRCh37: 7:37955979-37955979
GRCh38: 7:37916377-37916377
5 SFRP4 NM_003014.4(SFRP4):c.373T>A (p.Cys125Ser) SNV Likely Pathogenic
989455 rs1344808304 GRCh37: 7:37955767-37955767
GRCh38: 7:37916165-37916165
6 SFRP4 NM_003014.4(SFRP4):c.958C>A (p.Pro320Thr) SNV Benign
1287094 GRCh37: 7:37947164-37947164
GRCh38: 7:37907562-37907562
7 SFRP4 NM_003014.4(SFRP4):c.1019G>A (p.Arg340Lys) SNV Benign
1332946 GRCh37: 7:37947103-37947103
GRCh38: 7:37907501-37907501
8 SFRP4 NM_003014.4(SFRP4):c.786C>T (p.Arg262=) SNV Benign
1332947 GRCh37: 7:37951726-37951726
GRCh38: 7:37912124-37912124
9 SFRP4 NM_003014.4(SFRP4):c.567G>A (p.Thr189=) SNV Benign
1332948 GRCh37: 7:37953840-37953840
GRCh38: 7:37914238-37914238

Expression for Metaphyseal Dysplasia

Search GEO for disease gene expression data for Metaphyseal Dysplasia.

Pathways for Metaphyseal Dysplasia

GO Terms for Metaphyseal Dysplasia

Biological processes related to Metaphyseal Dysplasia according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 chondrocyte differentiation GO:0002062 9.99 RUNX2 PTH1R COL2A1
2 bone morphogenesis GO:0060349 9.88 SFRP4 MMP13 ACP5
3 endochondral ossification GO:0001958 9.85 RUNX2 MMP13 COL2A1
4 positive regulation of inositol phosphate biosynthetic process GO:0060732 9.83 PTH1R PTH
5 negative regulation of chondrocyte differentiation GO:0032331 9.8 NKX3-2 PTH PTHLH
6 cytosolic ribosome assembly GO:0042256 9.78 SBDS EFL1
7 skeletal system morphogenesis GO:0048705 9.76 RUNX2 NKX3-2 COL2A1
8 bone resorption GO:0045453 9.76 PTH1R PTH LRRK1 ACP5
9 cAMP metabolic process GO:0046058 9.73 PTHLH PTH
10 osteoblast development GO:0002076 9.73 RUNX2 PTHLH PTH1R
11 digestive system development GO:0055123 9.67 NKX3-2 CDKN1C
12 bone mineralization GO:0030282 9.65 MMP13 PTH PTH1R PTHLH SBDS
13 skeletal system development GO:0001501 9.5 RUNX2 PTHLH PTH1R PTH NKX3-2 COL2A1

Molecular functions related to Metaphyseal Dysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptide hormone receptor binding GO:0051428 8.92 PTHLH PTH

Sources for Metaphyseal Dysplasia

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....