PYL
MCID: PYL017
MIFTS: 52

Pyle Disease (PYL)

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

Aliases & Classifications for Pyle Disease

MalaCards integrated aliases for Pyle Disease:

Name: Pyle Disease 56 52 25 58 73
Metaphyseal Dysplasia 56 12 52 73 54 15 32
Pyle Metaphyseal Dysplasia 25 29 6 71
Pyle's Disease 12 52 25
Metaphyseal Dysplasia, Pyle Type 25 58
Pyl 56 73
Pyle's Metaphyseal Dysplasia Syndrome 25
Metaphyseal Dysplasia Pyle Type 52
Bakwin-Krida Syndrome 12
Pyle-Cohn Syndrome 12

Characteristics:

Orphanet epidemiological data:

58
pyle disease
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
homozygous patients reported no joint pain or muscle weakness
clinically asymptomatic heterozygous carriers may exhibit mild radiographic changes


HPO:

31
pyle disease:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0080019
OMIM 56 265900
MeSH 43 D010009
ICD10 32 Q78.5
MESH via Orphanet 44 C536252
ICD10 via Orphanet 33 Q78.5
UMLS via Orphanet 72 C0265294
Orphanet 58 ORPHA3005
MedGen 41 C0265294
UMLS 71 C0265294

Summaries for Pyle Disease

Genetics Home Reference : 25 Pyle disease is a disorder of the bones. Its hallmark feature is an abnormality of the long bones in the arms and legs in which the ends (metaphyses) of the bones are abnormally broad; the shape of the bones resembles a boat oar or paddle. The broad metaphyses are due to enlargement of the spongy inner layer of bone (trabecular bone). Although trabecular bone is expanded, the dense outermost layer of bone (cortical bone) is thinner than normal. As a result, the bones are fragile and fracture easily. The bone abnormalities in the legs commonly cause knock knees (genu valgum) in affected individuals. Other bone abnormalities can also occur in Pyle disease. Affected individuals may have widened collar bones (clavicles), ribs, or bones in the fingers and hands. Dental problems are common in Pyle disease, including delayed appearance (eruption) of permanent teeth and misalignment of the top and bottom teeth (malocclusion).

MalaCards based summary : Pyle Disease, also known as metaphyseal dysplasia, is related to cartilage-hair hypoplasia and spondyloepimetaphyseal dysplasia, strudwick type. An important gene associated with Pyle Disease is SFRP4 (Secreted Frizzled Related Protein 4), and among its related pathways/superpathways are Presynaptic function of Kainate receptors and G alpha (s) signalling events. Affiliated tissues include bone, cortex and brain, and related phenotypes are delayed eruption of teeth and genu valgum

Disease Ontology : 12 An osteochondrodysplasia that results in thinning and the tendency to fracture located in bone.

NIH Rare Diseases : 52 Pyle disease is a bone disorder characterized by knock knees (genu valgum ), relative constriction of the diaphysis or shaft of the bone and flaring of the metaphysis or end of the bone (Erlenmeyer flask deformity ), widening of the ribs and collarbones, flattening of the bones of the spine (platyspondyly), and thinning of outer (cortical) layer of bone. Other findings may include excessive bone formation of the skull. Pyle disease is caused by mutations in the SFRP4 gene and is inherited in an autosomal recessive manner. Treatment may include management of resulting bone fractures and other orthopedic concerns.

OMIM : 56 Pyle disease is characterized by long bones with wide and expanded trabecular metaphyses, thin cortical bone, and bone fragility. Fractures are common in Pyle disease, and fracture lines usually go through the abnormally wide metaphyses, revealing their fragility (summary by Kiper et al., 2016). (265900)

UniProtKB/Swiss-Prot : 73 Pyle disease: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures.

Related Diseases for Pyle Disease

Diseases related to Pyle Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 223)
# Related Disease Score Top Affiliating Genes
1 cartilage-hair hypoplasia 32.8 SBDS RMRP COL10A1
2 spondyloepimetaphyseal dysplasia, strudwick type 32.8 COL2A1 COL10A1
3 spondyloepimetaphyseal dysplasia, matrilin-3 related 32.3 DYM COMP COL2A1
4 metaphyseal chondrodysplasia, jansen type 31.1 PTHLH PTH1R PTH NKX3-2 GNAS GALNT3
5 coxa vara 31.0 COL2A1 COL10A1
6 skeletal dysplasias 30.3 PTH1R COMP COL2A1
7 hyperparathyroidism 30.2 PTHLH PTH FGF23
8 otospondylomegaepiphyseal dysplasia 30.1 COMP COL2A1 COL10A1
9 hyperostosis 30.1 GALNT3 FGF23 COL10A1
10 multiple epiphyseal dysplasia 30.0 PTHLH PTH1R COMP COL2A1
11 bone resorption disease 29.7 RUNX2 PTHLH PTH1R PTH FGF23
12 scoliosis 29.6 RUNX2 COMP COL2A1 COL10A1 CDKN1C
13 brachydactyly 29.4 RUNX2 PTHLH PTH GNAS COMP COL2A1
14 primary hyperparathyroidism 29.4 PTHLH PTH1R PTH GNAS FGF23
15 bone disease 28.9 RUNX2 PTHLH PTH1R PTH FGF23 CSF1R
16 odontochondrodysplasia 28.5 RUNX2 PTHLH PTH1R PTH DYM COMP
17 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 12.8
18 metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 12.8
19 spondylo-megaepiphyseal-metaphyseal dysplasia 12.8
20 metaphyseal dysplasia, spahr type 12.7
21 metaphyseal dysplasia without hypotrichosis 12.7
22 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 12.7
23 ulna metaphyseal dysplasia syndrome 12.6
24 osteosclerotic metaphyseal dysplasia 12.6
25 microspherophakia-metaphyseal dysplasia 12.6
26 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 12.6
27 metaphyseal dysplasia, braun-tinschert type 12.5
28 metaphyseal dysplasia, anetoderma, and optic atrophy 12.4
29 multiple metaphyseal dysplasia 12.4
30 shwachman-diamond type metaphyseal dysplasia 12.2
31 metaphyseal chondrodysplasia, schmid type 12.1
32 metaphyseal anadysplasia 12.0
33 metaphyseal acroscyphodysplasia 11.7
34 spondyloepimetaphyseal dysplasia, micromelic 11.7
35 spondyloepimetaphyseal dysplasia, sponastrime type 11.5
36 spondylometaphyseal dysplasia, algerian type 11.5
37 craniometaphyseal dysplasia, autosomal recessive 11.5
38 shwachman-diamond syndrome 1 11.5
39 spondyloenchondrodysplasia with immune dysregulation 11.3
40 shwachman-diamond syndrome 2 11.3
41 spondylometaphyseal dysplasia, sedaghatian type 11.2
42 say carpenter syndrome 11.2
43 spondylometaphyseal dysplasia, kozlowski type 11.2
44 cranioectodermal dysplasia 1 11.2
45 dyggve-melchior-clausen disease 11.2
46 spondylometaphyseal dysplasia, axial 11.2
47 anauxetic dysplasia 1 11.2
48 smith-mccort dysplasia 1 11.2
49 spondylometaphyseal dysplasia with cone-rod dystrophy 11.2
50 immunoskeletal dysplasia with neurodevelopmental abnormalities 11.2

Graphical network of the top 20 diseases related to Pyle Disease:



Diseases related to Pyle Disease

Symptoms & Phenotypes for Pyle Disease

Human phenotypes related to Pyle Disease:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 delayed eruption of teeth 31 occasional (7.5%) HP:0000684
2 genu valgum 31 HP:0002857
3 scoliosis 31 HP:0002650
4 muscle weakness 31 HP:0001324
5 mandibular prognathia 31 HP:0000303
6 carious teeth 31 HP:0000670
7 thickened calvaria 31 HP:0002684
8 arthralgia 31 HP:0002829
9 platyspondyly 31 HP:0000926
10 abnormality of the thorax 31 HP:0000765
11 reduced bone mineral density 31 HP:0004349
12 hypoplastic frontal sinuses 31 HP:0002738
13 limited elbow extension 31 HP:0001377
14 metaphyseal dysplasia 31 HP:0100255
15 metaphyseal widening 31 HP:0003016
16 absent paranasal sinuses 31 HP:0002689

Symptoms via clinical synopsis from OMIM:

56
Growth Height:
normal to tall stature

Skeletal Skull:
underdeveloped frontal sinuses
expansion of the diploe
absence of paranasal sinuses

Chest Ribs Sternum Clavicles And Scapulae:
marked widening of ribs
marked widening of clavicles

Skeletal Limbs:
genu valgum deformity, mild to severe
valgum deformity of elbows (in some patients)
marked metaphyseal widening of long bones ('erlenmeyer-flask deformity')
marked thinning of metaphyseal cortex
normal cortical thickness in middle part of diaphysis
more
Laboratory Abnormalities:
elevated osteocalcin
elevated bone-specific alkaline phosphatase
elevated procollagen type 1 n-terminal propeptide (p1np)

Skeletal:
decreased bone mineral density
chalk-like appearance of bone
fractures upon minimal trauma (in some patients)

Head And Neck Teeth:
delayed tooth eruption (in some patients)
failure to shed deciduous teeth (in some patients)

Skeletal Pelvis:
marked expansion of the ischial bones
marked expansion of the pubic bones

Skeletal Hands:
expansion of distal metacarpals
expansion of distal phalanges
undertubulation of metacarpals
undertubulation of phalanges

Clinical features from OMIM:

265900

MGI Mouse Phenotypes related to Pyle Disease:

45 (show all 16)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.42 AIRE COL10A1 COL2A1 COMP CSF1R DYM
2 endocrine/exocrine gland MP:0005379 10.36 AIRE COL10A1 CSF1R FGF23 GALNT3 GNAS
3 immune system MP:0005387 10.36 AIRE COL10A1 COL2A1 COMP CSF1R FGF23
4 hematopoietic system MP:0005397 10.35 AIRE COL10A1 CSF1R FGF23 GALNT3 GNAS
5 cellular MP:0005384 10.33 COL10A1 COL2A1 COMP CSF1R DYM GALNT3
6 craniofacial MP:0005382 10.31 COL10A1 COL2A1 CSF1R DYM GALNT3 GNAS
7 cardiovascular system MP:0005385 10.3 COL2A1 COMP FGF23 GALNT3 GNAS PTH
8 homeostasis/metabolism MP:0005376 10.3 AIRE COL2A1 COMP CSF1R FGF23 GALNT3
9 limbs/digits/tail MP:0005371 10.28 COL10A1 COL2A1 COMP CSF1R DYM FGF23
10 digestive/alimentary MP:0005381 10.22 AIRE COL2A1 FGF23 GALNT3 NKX3-2 PTH1R
11 mortality/aging MP:0010768 10.17 AIRE COL10A1 COL2A1 CSF1R FGF23 GNAS
12 liver/biliary system MP:0005370 9.91 AIRE COL2A1 GNAS PTH1R PTHLH RUNX2
13 normal MP:0002873 9.86 AIRE COL2A1 COMP CSF1R GNAS NKX3-2
14 renal/urinary system MP:0005367 9.7 COL2A1 DYM FGF23 GALNT3 GNAS PTHLH
15 respiratory system MP:0005388 9.61 AIRE COL2A1 FGF23 GNAS NKX3-2 PTH1R
16 skeleton MP:0005390 9.53 COL10A1 COL2A1 COMP CSF1R DYM FGF23

Drugs & Therapeutics for Pyle Disease

Search Clinical Trials , NIH Clinical Center for Pyle Disease

Genetic Tests for Pyle Disease

Genetic tests related to Pyle Disease:

# Genetic test Affiliating Genes
1 Pyle Metaphyseal Dysplasia 29 SFRP4

Anatomical Context for Pyle Disease

The Foundational Model of Anatomy Ontology organs/tissues related to Pyle Disease:

19
Bone

MalaCards organs/tissues related to Pyle Disease:

40
Bone, Cortex, Brain, T Cells, Eye, Neutrophil, Thymus

Publications for Pyle Disease

Articles related to Pyle Disease:

(show top 50) (show all 291)
# Title Authors PMID Year
1
Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. 56 6
27355534 2016
2
Pyle disease (metaphyseal dysplasia). 61 56
3612703 1987
3
Autosomal recessive inheritance of metaphyseal dysplasia (Pyle disease). 61 56
709903 1978
4
Pyle's disease (familial metaphyseal dysplasia). A presentation of two cases and argument for its separation from craniometaphyseal dysplasia. 61 56
5440013 1970
5
Familial metaphyseal dysplasia. 61 56
13245963 1955
6
Familial metaphyseal dysplasia, Pyle's disease. 61 56
13209025 1954
7
Familial metaphyseal dysplasia. 61 56
13080520 1953
8
Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum. 54 61
17701897 2007
9
COL2A1-related skeletal dysplasias with predominant metaphyseal involvement. 54 61
17163530 2007
10
Genetic disorders involving adrenal development. 54 61
17986825 2007
11
Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. 54 61
16252239 2005
12
Evolutionary comparison provides evidence for pathogenicity of RMRP mutations. 54 61
16244706 2005
13
Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. 54 61
14557425 2003
14
Spondylar dysplasia in type X collagenopathy. 54 61
11214689 2001
15
Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias. 54 61
7607655 1995
16
Spondylo-epi-metaphyseal dysplasia due to a homozygous missense mutation in the gene encoding Matrilin-3 (T120M). 61
32025536 2020
17
A novel homozygous LRRK1 stop gain mutation in a patient suspected with osteosclerotic metaphyseal dysplasia. 61
31571209 2020
18
'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations. 61
31413121 2020
19
Pyle's Disease: A human model of differentiated cortical and trabecular homeostasis. 61
29463445 2020
20
Wrist Joint Skeletal Changes in Children With Transfusion-Dependent Thalassemia. 61
32011549 2020
21
Metaphyseal dysplasia, Spahr type: a mimicker of rickets. 61
31413057 2019
22
Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation. 61
30982609 2019
23
The homozygous variant c.797G>A/p.(Cys266Tyr) in PISD is associated with a Spondyloepimetaphyseal dysplasia with large epiphyses and disturbed mitochondrial function. 61
30488656 2019
24
A novel NKX3-2 mutation associated with perinatal lethal phenotype of spondylo-megaepiphyseal-metaphyseal dysplasia in a neonate. 61
29704686 2019
25
Analysis of CDKN1C in fetal growth restriction and pregnancy loss. 61
31497289 2019
26
DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency. 61
30503519 2018
27
Confirmation of spondylo-epi-metaphyseal dysplasia with joint laxity, EXOC6B type. 61
30284759 2018
28
Clinical Characteristics and Genetic Causes of Infantile Exocrine Pancreatic Insufficiency in Chinese Patients: Study From a Tertiary Care Center. 61
30308536 2018
29
Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features. 61
29970384 2018
30
Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis. 61
30063090 2018
31
A three-generation family with metaphyseal dysplasia, maxillary hypoplasia and brachydactyly (MDMHB) due to intragenic RUNX2 duplication. 61
29891876 2018
32
[Spondyloenchondrodysplasia with immune dysregulation: a case report and literature review]. 61
30078244 2018
33
Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. 61
29766377 2018
34
A case of an infant suspected as IMAGE syndrome who were finally diagnosed with MIRAGE syndrome by targeted Mendelian exome sequencing. 61
29506479 2018
35
Evaluation of AAPM Reports 204 and 220: Estimation of effective diameter, water-equivalent diameter, and ellipticity ratios for chest, abdomen, pelvis, and head CT scans. 61
29178549 2018
36
Frontal cranioplasty in fronto-metaphyseal dysplasia. 61
28619674 2017
37
Expanding the spectrum of skeletal dysplasia with immunodeficiency: a commentary on identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. 61
28446799 2017
38
Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. 61
28331220 2017
39
A novel sequence variant in SFRP4 causing Pyle disease. 61
28100910 2017
40
Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. 61
27829680 2017
41
Additional three patients with Smith-McCort dysplasia due to novel RAB33B mutations. 61
28127940 2017
42
Metaphyseal dysplasia, Spahr type; missense MMP13 mutations in two Iraqi siblings. 61
27576021 2017
43
Pyle disease (metaphyseal dysplasia) presenting in two adult sisters. 61
27920870 2016
44
Cartilage Hair Hypoplasia: Two Unrelated Cases with g.70 A > G Mutation in RMRP Gene. 61
26830278 2016
45
Further evidence of POP1 mutations as the cause of anauxetic dysplasia. 61
27380734 2016
46
Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity. 61
27055475 2016
47
Metaphyseal dysplasia associated with chronic facial nerve palsy. 61
26847543 2016
48
Progressive Pseudorheumatoid Dysplasia Misdiagnosed as Seronegative Juvenile Idiopathic Arthritis. 61
27587938 2016
49
[Multiple long bone fractures in a child with pycnodysostosis. A case report]. 61
27164353 2016
50
Pyle metaphyseal dysplasia in an African child: Case report and review of the literature. 61
27245543 2016

Variations for Pyle Disease

ClinVar genetic disease variations for Pyle Disease:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SFRP4 NM_003014.3(SFRP4):c.499dupGduplication Pathogenic 242995 rs879255603 7:37954001-37954002 7:37914399-37914400
2 SFRP4 NM_003014.3(SFRP4):c.694C>TSNV Pathogenic 242996 rs755007671 7:37951818-37951818 7:37912216-37912216
3 SFRP4 NM_003014.3(SFRP4):c.481_487delGTACAGGdeletion Pathogenic 242997 rs879253778 7:37954014-37954020 7:37914412-37914418

Expression for Pyle Disease

Search GEO for disease gene expression data for Pyle Disease.

Pathways for Pyle Disease

GO Terms for Pyle Disease

Biological processes related to Pyle Disease according to GeneCards Suite gene sharing:

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 regulation of gene expression GO:0010468 9.83 RUNX2 PTHLH PTH COMP COL2A1
2 multicellular organism growth GO:0035264 9.77 GNAS COMP CDKN1C
3 cartilage development GO:0051216 9.76 GNAS COMP COL2A1
4 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.76 PTHLH PTH1R PTH GNAS
5 bone development GO:0060348 9.73 GNAS DYM COL2A1
6 skeletal system morphogenesis GO:0048705 9.71 RUNX2 NKX3-2 COL2A1
7 chondrocyte differentiation GO:0002062 9.69 RUNX2 PTH1R COL2A1
8 ossification GO:0001503 9.67 RUNX2 PTH1R COMP COL2A1
9 endochondral ossification GO:0001958 9.65 RUNX2 GNAS COL2A1
10 chondrocyte development GO:0002063 9.6 RUNX2 COMP
11 digestive system development GO:0055123 9.58 NKX3-2 CDKN1C
12 bone resorption GO:0045453 9.58 PTH1R PTH LRRK1
13 positive regulation of inositol phosphate biosynthetic process GO:0060732 9.57 PTH1R PTH
14 response to parathyroid hormone GO:0071107 9.55 PTH GNAS
15 genetic imprinting GO:0071514 9.52 GNAS CDKN1C
16 negative regulation of chondrocyte differentiation GO:0032331 9.5 PTHLH PTH NKX3-2
17 cAMP metabolic process GO:0046058 9.49 PTHLH PTH
18 bone mineralization GO:0030282 9.46 SBDS PTHLH PTH1R COMP
19 osteoblast development GO:0002076 9.43 RUNX2 PTHLH PTH1R
20 skeletal system development GO:0001501 9.32 RUNX2 PTHLH PTH1R PTH NKX3-2 GNAS
21 phosphate ion homeostasis GO:0055062 9.13 SFRP4 PTH FGF23

Molecular functions related to Pyle Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.09 SFRP4 SBDS RUNX2 PTHLH PTH1R PTH
2 proteoglycan binding GO:0043394 8.96 COMP COL2A1
3 peptide hormone receptor binding GO:0051428 8.62 PTHLH PTH

Sources for Pyle Disease

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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