MCID: PYL017
MIFTS: 50

Pyle Disease

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

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.

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.

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

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 98)
# Related Disease Score Top Affiliating Genes
1 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 33.9 CDKN1C NR0B1
2 metaphyseal chondrodysplasia, schmid type 33.1 COL10A1 RMRP
3 spondyloepimetaphyseal dysplasia, strudwick type 31.9 COL10A1 COL2A1
4 metaphyseal chondrodysplasia, jansen type 30.8 COL2A1 PTH1R PTHLH
5 cartilage-hair hypoplasia 30.5 COL10A1 RMRP
6 skeletal dysplasias 28.8 COL2A1 PTH1R PTHLH
7 spondylo-megaepiphyseal-metaphyseal dysplasia 12.4
8 metaphyseal dysplasia, spahr type 12.4
9 osteosclerotic metaphyseal dysplasia 12.3
10 metaphyseal dysplasia maxillary hypoplasia brachydactyly 12.3
11 intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 12.3
12 metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 12.3
13 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 12.2
14 metaphyseal dysplasia without hypotrichosis 12.2
15 ulna metaphyseal dysplasia syndrome 12.2
16 metaphyseal dysplasia, braun-tinschert type 12.1
17 microspherophakia-metaphyseal dysplasia 12.1
18 metaphyseal dysplasia, anetoderma, and optic atrophy 12.1
19 shwachman-diamond type metaphyseal dysplasia 11.9
20 multiple joint dislocations metaphyseal dysplasia 11.9
21 metaphyseal anadysplasia 11.7
22 verloes van maldergem marneffe syndrome 11.7
23 spondyloepimetaphyseal dysplasia, micromelic 11.4
24 craniometaphyseal dysplasia, autosomal dominant 11.4
25 metaphyseal acroscyphodysplasia 11.2
26 spondylometaphyseal dysplasia, sedaghatian type 10.9
27 spondyloepimetaphyseal dysplasia, sponastrime type 10.9
28 spondyloepimetaphyseal dysplasia, matrilin-3 related 10.9
29 say carpenter syndrome 10.9
30 spondylometaphyseal dysplasia, algerian type 10.9
31 craniometaphyseal dysplasia, autosomal recessive 10.9
32 dyggve-melchior-clausen disease 10.9
33 spondylometaphyseal dysplasia, axial 10.9
34 anauxetic dysplasia 1 10.9
35 smith-mccort dysplasia 1 10.9
36 spondyloenchondrodysplasia with immune dysregulation 10.9
37 immunoskeletal dysplasia with neurodevelopmental abnormalities 10.9
38 shwachman-diamond syndrome 2 10.9
39 metaphyseal dysostosis-intellectual disability-conductive deafness syndrome 10.9
40 frontometaphyseal dysplasia 10.6
41 corneal dystrophy, subepithelial mucinous 10.4 COL10A1 RMRP
42 coxa vara 10.4 COL10A1 COL2A1
43 oncogenic osteomalacia 10.4 PTHLH SFRP4
44 cartilage disease 10.3 COL10A1 COL2A1
45 adrenal cortical hypofunction 10.2 AIRE NR0B1
46 metaphyseal dysostosis, mental retardation, and conductive deafness 10.1
47 adrenal cortex disease 10.1 AIRE NR0B1
48 gestational trophoblastic neoplasm 10.1 CDKN1C NR0B1
49 adrenal gland disease 10.1 AIRE NR0B1
50 brachydactyly 10.1

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 15)
# 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 absent paranasal sinuses 32 HP:0002689

MGI Mouse Phenotypes related to Pyle Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.65 PTH1R PTHLH SFRP4 AIRE COL2A1
2 immune system MP:0005387 9.63 PTH1R PTHLH SFRP4 AIRE COL10A1 COL2A1
3 limbs/digits/tail MP:0005371 9.35 PTH1R PTHLH SFRP4 COL10A1 COL2A1
4 respiratory system MP:0005388 9.02 PTH1R PTHLH SFRP4 AIRE COL2A1

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

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 117)
# 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
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
5
Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia. ( 28331220 )
2017
6
Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. ( 27829680 )
2017
7
A novel sequence variant in SFRP4 causing Pyle disease. ( 28100910 )
2017
8
Pyle disease (metaphyseal dysplasia) presenting in two adult sisters. ( 27920870 )
2016
9
Metaphyseal dysplasia associated with chronic facial nerve palsy. ( 26847543 )
2016
10
Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity. ( 27055475 )
2016
11
Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia: A Case Report. ( 27149441 )
2016
12
Japanese familial case with metaphyseal dysplasia, Schmid Type caused by the p.T555P mutation in the COL10A1 gene. ( 25678758 )
2015
13
Osteosclerotic metaphyseal dysplasia with extensive interstitial pulmonary lesions: a case report and literature review. ( 26084987 )
2015
14
Metaphyseal Dysplasia with Maxillary Hypoplasia and Brachydactyly in a Finnish Woman: First Confirmation of a Duplication in RUNX2 as Pathogenic Variant. ( 25311905 )
2014
15
MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type. ( 24648384 )
2014
16
Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2. ( 23290074 )
2013
17
An extremely rare case: osteosclerotic metaphyseal dysplasia. ( 23610867 )
2013
18
A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia. ( 23239615 )
2013
19
Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R. ( 23950054 )
2013
20
Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia. ( 22791571 )
2012
21
The fate of the hip in spondylo-epi-metaphyseal dysplasia: clinical and radiological evaluation of adults with SEMD Handigodu type. ( 22116201 )
2012
22
Homozygous inactivating mutations in the NKX3-2 gene result in spondylo-megaepiphyseal-metaphyseal dysplasia. ( 20004766 )
2009
23
Spondylo-epi-metaphyseal dysplasia. ( 18328979 )
2008
24
Pyle metaphyseal dysplasia. ( 18451455 )
2008
25
WITHDRAWN: Familial Degenerative Encephalopathy with Intracranial Calcification and Metaphyseal Dysplasia. ( 19016590 )
2008
26
Metaphyseal dysplasia of Braun-Tinschert type: report of a Japanese girl. ( 16691581 )
2006
27
A new familial case of spondylo-epi-metaphyseal dysplasia with multiple dislocations Hall type (leptodactylic form). ( 15602087 )
2005
28
A case with spondylo-metaphyseal dysplasia type A4. ( 15517830 )
2004
29
Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD. ( 15121775 )
2004
30
Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures. ( 12497229 )
2003
31
A new syndrome of &amp;quot;spondylo-epi-metaphyseal dysplasia: mixed type&amp;quot;. ( 12589493 )
2003
32
A case with Pyle type metaphyseal dysplasia: clinical, radiological and histological evaluation. ( 14738111 )
2003
33
Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. ( 14557425 )
2003
34
Spondylo-megaepiphyseal-metaphyseal dysplasia: an unusual bone dysplasia. ( 13680008 )
2003
35
Metaphyseal dysplasia: a new autosomal dominant type in a large German kindred. ( 11343343 )
2001
36
Spondylo-epi-metaphyseal dysplasia with normal stature: a case followed from infancy to skeletal maturity. ( 10457852 )
1999
37
IMAGe, a new clinical association of intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. ( 10599684 )
1999
38
Metaphyseal anadysplasia type II: a new regressive metaphyseal dysplasia. ( 9799299 )
1998
39
A unique lethal spondylocostal metaphyseal dysplasia: a case report. ( 9571281 )
1998
40
Esophageal atresia with distal tracheoesophageal fistula in a patient with fronto-metaphyseal dysplasia. ( 9375915 )
1997
41
Intracranial calcifications, epilepsy, and optic atrophy associated with metaphyseal dysplasia: a case report. ( 9339870 )
1997
42
Major central nervous system malformation in &amp;quot;micromelic dwarfism with cone epiphyses, metaphyseal dysplasia and vertebral segmentation defects&amp;quot;. ( 8986289 )
1997
43
Postosteotomy healing in Pyle's disease (familial metaphyseal dysplasia). A case report. ( 9269176 )
1997
44
Micromelic dwarfism with cone epiphyses, metaphyseal dysplasia, and vertebral segmentation defects. ( 8669445 )
1996
45
Metaphyseal dysplasia-Bellini type. Report of two cases. ( 7754130 )
1995
46
Dutch variant of Bellini metaphyseal dysplasia: report of two siblings. ( 7487766 )
1995
47
Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias. ( 7607655 )
1995
48
Japanese type of spondylo-metaphyseal dysplasia. ( 7936797 )
1994
49
Osteosclerotic metaphyseal dysplasia. ( 8255649 )
1993
50
Spondylo-metaphyseal dysplasia corner fracture type (a cautionary tale). ( 8480052 )
1993

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 10.83 CDKN1C COL10A1 COL2A1 PTH1R PTHLH
2 10.81 CDKN1C PTH1R
3 10.55 PTH1R PTHLH

GO Terms for Pyle Disease

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

# Name GO ID Score Top Affiliating Genes
1 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.4 PTH1R PTHLH
2 negative regulation of DNA binding transcription factor activity GO:0043433 9.37 NR0B1 SFRP4
3 collagen catabolic process GO:0030574 9.32 COL10A1 COL2A1
4 chondrocyte differentiation GO:0002062 9.26 COL2A1 PTH1R
5 bone mineralization GO:0030282 9.16 PTH1R PTHLH
6 osteoblast development GO:0002076 8.96 PTH1R PTHLH
7 skeletal system development GO:0001501 8.92 COL10A1 COL2A1 PTH1R PTHLH

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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