PYL
MCID: PYL017
MIFTS: 37

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 20 43 58 73
Metaphyseal Dysplasia, Pyle Type 57 43 58 73
Pyle Metaphyseal Dysplasia 43 29 6 71
Pyle's Disease 20 43
Pyl 57 73
Pyle's Metaphyseal Dysplasia Syndrome 43
Metaphyseal Dysplasia Pyle Type 20
Metaphyseal Dysplasia 20

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 05-Mar-2021)
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:

OMIM® 57 265900
MeSH 44 D010009
MESH via Orphanet 45 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

MedlinePlus Genetics : 43 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, pyle type, is related to intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies and metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly. An important gene associated with Pyle Disease is SFRP4 (Secreted Frizzled Related Protein 4). Affiliated tissues include bone, cortex and eye, and related phenotypes are delayed eruption of teeth and scoliosis

GARD : 20 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® : 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) (Updated 05-Mar-2021)

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 151)
# Related Disease Score Top Affiliating Genes
1 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 11.8
2 metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly 11.7
3 spondylo-megaepiphyseal-metaphyseal dysplasia 11.7
4 metaphyseal dysplasia without hypotrichosis 11.6
5 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 11.6
6 ulna metaphyseal dysplasia syndrome 11.5
7 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 11.5
8 metaphyseal dysplasia, spahr type 11.5
9 osteosclerotic metaphyseal dysplasia 11.5
10 microspherophakia-metaphyseal dysplasia 11.5
11 metaphyseal chondrodysplasia, schmid type 11.3
12 metaphyseal anadysplasia 11.3
13 shwachman-diamond syndrome 1 11.3
14 metaphyseal dysplasia, braun-tinschert type 11.2
15 spondyloepimetaphyseal dysplasia, micromelic 11.2
16 metaphyseal dysplasia, anetoderma, and optic atrophy 11.2
17 cartilage-hair hypoplasia 11.2
18 spondyloenchondrodysplasia with immune dysregulation 11.1
19 shwachman-diamond syndrome 2 11.1
20 metaphyseal dysplasia 11.1
21 multiple metaphyseal dysplasia 11.1
22 spondyloepimetaphyseal dysplasia, borochowitz-cormier-daire type 11.1
23 metaphyseal chondrodysplasia, jansen type 11.0
24 metaphyseal acroscyphodysplasia 11.0
25 spondylometaphyseal dysplasia, sedaghatian type 11.0
26 say carpenter syndrome 11.0
27 spondylometaphyseal dysplasia, algerian type 11.0
28 craniometaphyseal dysplasia, autosomal recessive 11.0
29 spondylometaphyseal dysplasia, kozlowski type 11.0
30 dyggve-melchior-clausen disease 11.0
31 ghosal hematodiaphyseal dysplasia 11.0
32 spondylometaphyseal dysplasia, axial 11.0
33 anauxetic dysplasia 1 11.0
34 smith-mccort dysplasia 1 11.0
35 spondylometaphyseal dysplasia with cone-rod dystrophy 11.0
36 immunoskeletal dysplasia with neurodevelopmental abnormalities 11.0
37 cranioectodermal dysplasia 11.0
38 metaphyseal dysostosis-intellectual disability-conductive deafness syndrome 11.0
39 frontometaphyseal dysplasia 10.3
40 brachydactyly 10.3
41 dwarfism 10.3
42 autosomal recessive disease 10.2
43 bone disease 10.2
44 rickets 10.2
45 osteopetrosis 10.2
46 hypotonia 10.2
47 coxa vara 10.2
48 frontometaphyseal dysplasia 1 10.2
49 scoliosis 10.2
50 bone resorption disease 10.1

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 scoliosis 31 HP:0002650
3 muscle weakness 31 HP:0001324
4 mandibular prognathia 31 HP:0000303
5 carious teeth 31 HP:0000670
6 thickened calvaria 31 HP:0002684
7 genu valgum 31 HP:0002857
8 reduced bone mineral density 31 HP:0004349
9 arthralgia 31 HP:0002829
10 platyspondyly 31 HP:0000926
11 hypoplastic frontal sinuses 31 HP:0002738
12 metaphyseal dysplasia 31 HP:0100255
13 metaphyseal widening 31 HP:0003016
14 limited elbow extension 31 HP:0001377
15 abnormal thorax morphology 31 HP:0000765
16 absent paranasal sinuses 31 HP:0002689

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Pyle Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 8.62 CSF1R SFRP4

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

MalaCards organs/tissues related to Pyle Disease:

40
Bone, Cortex, Eye, Brain

Publications for Pyle Disease

Articles related to Pyle Disease:

(show all 21)
# Title Authors PMID Year
1
Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. 57 6
27355534 2016
2
The First Report of Biallelic Missense Mutations in the SFRP4 Gene Causing Pyle Disease in Two Siblings. 6 61
33193738 2020
3
Pyle disease (metaphyseal dysplasia). 61 57
3612703 1987
4
Autosomal recessive inheritance of metaphyseal dysplasia (Pyle disease). 57 61
709903 1978
5
Pyle's disease (familial metaphyseal dysplasia). A presentation of two cases and argument for its separation from craniometaphyseal dysplasia. 57
5440013 1970
6
Familial metaphyseal dysplasia. 57
13245963 1955
7
Familial metaphyseal dysplasia, Pyle's disease. 57
13209025 1954
8
Familial metaphyseal dysplasia. 57
13080520 1953
9
Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation. 61
30982609 2019
10
A novel sequence variant in SFRP4 causing Pyle disease. 61
28100910 2017
11
Pyle disease (metaphyseal dysplasia) presenting in two adult sisters. 61
27920870 2016
12
Metaphyseal dysplasia associated with chronic facial nerve palsy. 61
26847543 2016
13
Pyle metaphyseal dysplasia in an African child: Case report and review of the literature. 61
27245543 2016
14
Intracranial Hypertension in Children: Etiologies, Clinical Features, and Outcome. 61
25762586 2015
15
Pyle metaphyseal dysplasia. 61
18451455 2008
16
[Pyle disease]. 61
11528890 2001
17
Heterogeneity in Schwartz-Jampel chondrodystrophic myotonia. 61
9083764 1997
18
Multicentric fibromatosis with metaphyseal dysplasia. 61
8475296 1993
19
The radiological manifestations of metaphyseal dysplasia (Pyle disease). 61
465917 1979
20
A review of the osteopetroses. 61
335376 1977
21
Roentgenography of the ear and eye in Pyle disease. 61
4364304 1974

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.481_487delGTACAGG Deletion Pathogenic 242997 rs879253778 7:37954014-37954020 7:37914412-37914418
2 SFRP4 NM_003014.3(SFRP4):c.499dupG Duplication Pathogenic 242995 rs879255603 7:37954001-37954002 7:37914399-37914400
3 SFRP4 NM_003014.3(SFRP4):c.694C>T SNV Pathogenic 242996 rs755007671 7:37951818-37951818 7:37912216-37912216
4 SFRP4 NM_003014.4(SFRP4):c.161C>A (p.Ala54Asp) SNV Likely pathogenic 989454 7:37955979-37955979 7:37916377-37916377
5 SFRP4 NM_003014.4(SFRP4):c.373T>A (p.Cys125Ser) SNV Likely pathogenic 989455 7:37955767-37955767 7:37916165-37916165

Expression for Pyle Disease

Search GEO for disease gene expression data for Pyle Disease.

Pathways for Pyle Disease

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 cell surface GO:0009986 8.62 SFRP4 CSF1R

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

# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 8.96 SFRP4 CSF1R
2 negative regulation of cell proliferation GO:0008285 8.62 SFRP4 CSF1R

Sources for Pyle Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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