PYL
MCID: PYL017
MIFTS: 48

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 57 53 25 59 75
Metaphyseal Dysplasia 57 12 53 75 55 15
Pyle Metaphyseal Dysplasia 25 29 6 73
Pyle's Disease 12 53 25
Metaphyseal Dysplasia, Pyle Type 25 59
Pyl 57 75
Pyle's Metaphyseal Dysplasia Syndrome 25
Metaphyseal Dysplasia Pyle Type 53
Bakwin-Krida Syndrome 12
Pyle-Cohn Syndrome 12

Characteristics:

Orphanet epidemiological data:

59
pyle disease
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
pyle disease:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 265900
Disease Ontology 12 DOID:0080019
Orphanet 59 ORPHA3005
UMLS via Orphanet 74 C0265294
MESH via Orphanet 45 C536252
ICD10 via Orphanet 34 Q78.5
MedGen 42 C0265294
MeSH 44 D010009
ICD10 33 Q78.5
UMLS 73 C0265294

Summaries for Pyle Disease

NIH Rare Diseases : 53 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.

MalaCards based summary : Pyle Disease, also known as metaphyseal dysplasia, is related to intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies and metaphyseal chondrodysplasia, schmid type. An important gene associated with Pyle Disease is SFRP4 (Secreted Frizzled Related Protein 4), and among its related pathways/superpathways are Endochondral Ossification and Transcription_Role of VDR in regulation of genes involved in osteoporosis. Affiliated tissues include bone, cortex and eye, and related phenotypes are genu valgum and muscle weakness

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

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.

OMIM : 57 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 : 75 Pyle disease: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures.

Wikipedia : 76 Metaphyseal dysplasia, also known as Pyle''s disease,Pyle''s syndrome, Pyle-Cohn syndrome, and... more...

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 86)
# Related Disease Score Top Affiliating Genes
1 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 34.1 CDKN1C NR0B1
2 metaphyseal chondrodysplasia, schmid type 32.9 COL10A1 RMRP
3 metaphyseal chondrodysplasia, jansen type 31.9 COL2A1 PTH1R
4 spondyloepimetaphyseal dysplasia, strudwick type 31.7 COL10A1 COL2A1
5 anauxetic dysplasia 1 31.6 POP1 RMRP
6 cartilage-hair hypoplasia 30.0 COL10A1 POP1 RMRP
7 spondylo-megaepiphyseal-metaphyseal dysplasia 12.6
8 metaphyseal dysplasia, spahr type 12.6
9 osteosclerotic metaphyseal dysplasia 12.5
10 ulna metaphyseal dysplasia syndrome 12.5
11 metaphyseal dysplasia maxillary hypoplasia brachydactyly 12.5
12 intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 12.4
13 metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 12.4
14 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 12.4
15 metaphyseal dysplasia without hypotrichosis 12.4
16 metaphyseal dysplasia, braun-tinschert type 12.2
17 microspherophakia-metaphyseal dysplasia 12.2
18 metaphyseal dysplasia, anetoderma, and optic atrophy 12.2
19 shwachman-diamond type metaphyseal dysplasia 12.1
20 multiple joint dislocations metaphyseal dysplasia 12.1
21 metaphyseal anadysplasia 11.8
22 verloes van maldergem marneffe syndrome 11.8
23 spondyloepimetaphyseal dysplasia, micromelic 11.5
24 spondyloepimetaphyseal dysplasia, matrilin-3 related 11.4
25 metaphyseal acroscyphodysplasia 11.4
26 craniometaphyseal dysplasia, autosomal dominant 11.4
27 shwachman-diamond syndrome 2 11.1
28 spondylometaphyseal dysplasia, sedaghatian type 11.1
29 spondyloepimetaphyseal dysplasia, sponastrime type 11.1
30 say carpenter syndrome 11.1
31 spondylometaphyseal dysplasia, algerian type 11.0
32 craniometaphyseal dysplasia, autosomal recessive 11.0
33 dyggve-melchior-clausen disease 11.0
34 shwachman-diamond syndrome 1 11.0
35 spondylometaphyseal dysplasia, axial 11.0
36 smith-mccort dysplasia 1 11.0
37 spondyloenchondrodysplasia with immune dysregulation 11.0
38 immunoskeletal dysplasia with neurodevelopmental abnormalities 11.0
39 metaphyseal dysostosis-intellectual disability-conductive deafness syndrome 11.0
40 frontometaphyseal dysplasia 10.7
41 metaphyseal dysostosis, mental retardation, and conductive deafness 10.3
42 brachydactyly 10.2
43 dwarfism 10.1
44 corneal dystrophy, subepithelial mucinous 10.1 COL10A1 RMRP
45 coxa vara 10.1 COL10A1 COL2A1
46 cartilage disease 10.1 COL10A1 COL2A1
47 gestational trophoblastic neoplasm 10.1 CDKN1C NR0B1
48 trophoblastic neoplasm 10.1 CDKN1C NR0B1
49 adrenal cortical hypofunction 10.0 AIRE NR0B1
50 macroglossia 10.0 CDKN1C COL2A1

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



Diseases related to Pyle Disease

Symptoms & Phenotypes for Pyle Disease

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Pyle Disease:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 genu valgum 32 HP:0002857
2 muscle weakness 32 HP:0001324
3 scoliosis 32 HP:0002650
4 mandibular prognathia 32 HP:0000303
5 carious teeth 32 HP:0000670
6 thickened calvaria 32 HP:0002684
7 arthralgia 32 HP:0002829
8 delayed eruption of teeth 32 occasional (7.5%) HP:0000684
9 platyspondyly 32 HP:0000926
10 abnormality of the thorax 32 HP:0000765
11 reduced bone mineral density 32 HP:0004349
12 hypoplastic frontal sinuses 32 HP:0002738
13 limited elbow extension 32 HP:0001377
14 metaphyseal dysplasia 32 HP:0100255
15 metaphyseal widening 32 HP:0003016
16 absent paranasal sinuses 32 HP:0002689

MGI Mouse Phenotypes related to Pyle Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 8.92 COL10A1 COL2A1 PTH1R SFRP4

Drugs & Therapeutics for Pyle Disease

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Skeletal Disorders and Short Stature Completed NCT00001754

Search 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

MalaCards organs/tissues related to Pyle Disease:

41
Bone, Cortex, Eye, Neutrophil, Skin, Adrenal Cortex

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

19
Bone

Publications for Pyle Disease

Articles related to Pyle Disease:

(show top 50) (show all 120)
# Title Authors Year
1
A three-generation family with metaphyseal dysplasia, maxillary hypoplasia and brachydactyly (MDMHB) due to intragenic RUNX2 duplication. ( 29891876 )
2018
2
Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. ( 29766377 )
2018
3
A novel NKX3-2 mutation associated with perinatal lethal phenotype of spondylo-megaepiphyseal-metaphyseal dysplasia in a neonate. ( 29704686 )
2018
4
Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis. ( 30063090 )
2018
5
Confirmation of spondylo-epi-metaphyseal dysplasia with joint laxity, EXOC6B type. ( 30284759 )
2018
6
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. ( 28446799 )
2017
7
Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. ( 28331220 )
2017
8
Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. ( 27829680 )
2017
9
A novel sequence variant in SFRP4 causing Pyle disease. ( 28100910 )
2017
10
Metaphyseal dysplasia, Spahr type; missense MMP13 mutations in two Iraqi siblings. ( 27576021 )
2017
11
Frontal cranioplasty in fronto-metaphyseal dysplasia. ( 28619674 )
2017
12
Pyle disease (metaphyseal dysplasia) presenting in two adult sisters. ( 27920870 )
2016
13
Metaphyseal dysplasia associated with chronic facial nerve palsy. ( 26847543 )
2016
14
Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity. ( 27055475 )
2016
15
Pyle metaphyseal dysplasia in an African child: Case report and review of the literature. ( 27245543 )
2016
16
Japanese familial case with metaphyseal dysplasia, Schmid Type caused by the p.T555P mutation in the COL10A1 gene. ( 25678758 )
2015
17
Osteosclerotic metaphyseal dysplasia with extensive interstitial pulmonary lesions: a case report and literature review. ( 26084987 )
2015
18
Metaphyseal Dysplasia with Maxillary Hypoplasia and Brachydactyly in a Finnish Woman: First Confirmation of a Duplication in RUNX2 as Pathogenic Variant. ( 25311905 )
2014
19
MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type. ( 24648384 )
2014
20
Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2. ( 23290074 )
2013
21
An extremely rare case: osteosclerotic metaphyseal dysplasia. ( 23610867 )
2013
22
A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia. ( 23239615 )
2013
23
Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R. ( 23950054 )
2013
24
Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia. ( 22791571 )
2012
25
The fate of the hip in spondylo-epi-metaphyseal dysplasia: clinical and radiological evaluation of adults with SEMD Handigodu type. ( 22116201 )
2012
26
Homozygous inactivating mutations in the NKX3-2 gene result in spondylo-megaepiphyseal-metaphyseal dysplasia. ( 20004766 )
2009
27
Spondylo-epi-metaphyseal dysplasia. ( 18328979 )
2008
28
Pyle metaphyseal dysplasia. ( 18451455 )
2008
29
WITHDRAWN: Familial Degenerative Encephalopathy with Intracranial Calcification and Metaphyseal Dysplasia. ( 19016590 )
2008
30
Metaphyseal dysplasia of Braun-Tinschert type: report of a Japanese girl. ( 16691581 )
2006
31
A new familial case of spondylo-epi-metaphyseal dysplasia with multiple dislocations Hall type (leptodactylic form). ( 15602087 )
2005
32
A case with spondylo-metaphyseal dysplasia type A4. ( 15517830 )
2004
33
Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD. ( 15121775 )
2004
34
Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures. ( 12497229 )
2003
35
A new syndrome of &amp;quot;spondylo-epi-metaphyseal dysplasia: mixed type&amp;quot;. ( 12589493 )
2003
36
A case with Pyle type metaphyseal dysplasia: clinical, radiological and histological evaluation. ( 14738111 )
2003
37
Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. ( 14557425 )
2003
38
Spondylo-megaepiphyseal-metaphyseal dysplasia: an unusual bone dysplasia. ( 13680008 )
2003
39
Metaphyseal dysplasia: a new autosomal dominant type in a large German kindred. ( 11343343 )
2001
40
Spondylo-epi-metaphyseal dysplasia with normal stature: a case followed from infancy to skeletal maturity. ( 10457852 )
1999
41
IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. ( 10599684 )
1999
42
Metaphyseal anadysplasia type II: a new regressive metaphyseal dysplasia. ( 9799299 )
1998
43
A unique lethal spondylocostal metaphyseal dysplasia: a case report. ( 9571281 )
1998
44
Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto-metaphyseal dysplasia. ( 9375915 )
1997
45
Intracranial calcifications, epilepsy, and optic atrophy associated with metaphyseal dysplasia: a case report. ( 9339870 )
1997
46
Major central nervous system malformation in &amp;quot;micromelic dwarfism with cone epiphyses, metaphyseal dysplasia and vertebral segmentation defects&amp;quot;. ( 8986289 )
1997
47
Postosteotomy healing in Pyle's disease (familial metaphyseal dysplasia). A case report. ( 9269176 )
1997
48
Micromelic dwarfism with cone epiphyses, metaphyseal dysplasia, and vertebral segmentation defects. ( 8669445 )
1996
49
Metaphyseal dysplasia-Bellini type. Report of two cases. ( 7754130 )
1995
50
Dutch variant of Bellini metaphyseal dysplasia: report of two siblings. ( 7487766 )
1995

Variations for Pyle Disease

ClinVar genetic disease variations for Pyle Disease:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SFRP4 NM_003014.3(SFRP4): c.499dupG duplication Pathogenic rs879255603 GRCh37 Chromosome 7, 37954002: 37954002
2 SFRP4 NM_003014.3(SFRP4): c.499dupG duplication Pathogenic rs879255603 GRCh38 Chromosome 7, 37914400: 37914400
3 SFRP4 NM_003014.3(SFRP4): c.694C> T single nucleotide variant Pathogenic rs755007671 GRCh37 Chromosome 7, 37951818: 37951818
4 SFRP4 NM_003014.3(SFRP4): c.694C> T single nucleotide variant Pathogenic rs755007671 GRCh38 Chromosome 7, 37912216: 37912216
5 SFRP4 NM_003014.3(SFRP4): c.481_487delGTACAGG deletion Pathogenic rs879253778 GRCh38 Chromosome 7, 37914412: 37914418
6 SFRP4 NM_003014.3(SFRP4): c.481_487delGTACAGG deletion Pathogenic rs879253778 GRCh37 Chromosome 7, 37954014: 37954020

Expression for Pyle Disease

Search GEO for disease gene expression data for Pyle Disease.

Pathways for Pyle Disease

Pathways related to Pyle Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.74 CDKN1C COL10A1 COL2A1 PTH1R
2 10.61 CDKN1C PTH1R

GO Terms for Pyle Disease

Cellular components related to Pyle Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen trimer GO:0005581 8.96 COL10A1 COL2A1
2 ribonuclease MRP complex GO:0000172 8.62 POP1 RMRP

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

# Name GO ID Score Top Affiliating Genes
1 negative regulation of DNA-binding transcription factor activity GO:0043433 9.32 NR0B1 SFRP4
2 RNA phosphodiester bond hydrolysis GO:0090501 9.26 POP1 RMRP
3 chondrocyte differentiation GO:0002062 9.16 COL2A1 PTH1R
4 adrenal gland development GO:0030325 8.96 CDKN1C NR0B1
5 skeletal system development GO:0001501 8.92 CDKN1C COL10A1 COL2A1 PTH1R

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent conferring tensile strength GO:0030020 8.96 COL10A1 COL2A1
2 ribonuclease MRP activity GO:0000171 8.62 POP1 RMRP

Sources for Pyle Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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