OPSMD
MCID: OPS002
MIFTS: 36

Opsismodysplasia (OPSMD)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Opsismodysplasia

MalaCards integrated aliases for Opsismodysplasia:

Name: Opsismodysplasia 57 75 53 59 74 37 29 13 6 40 72
Opsmd 57 74

Characteristics:

Orphanet epidemiological data:

59
opsismodysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
may result in death in neonatal period or early childhood


HPO:

32
opsismodysplasia:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 258480
KEGG 37 H01828
MeSH 44 D010009
MESH via Orphanet 45 C537122
ICD10 via Orphanet 34 Q78.8
UMLS via Orphanet 73 C0432219
Orphanet 59 ORPHA2746
MedGen 42 C0432219
UMLS 72 C0432219

Summaries for Opsismodysplasia

KEGG : 37
Opsismodysplasia (OPS) is a rare, autosomal-recessive skeletal dysplasia primarily characterized by growth plate defects and delayed bone maturation. Its clinical features are rhizomelic micromelia and facial dysmorphism, including prominent brow, large fontanels, depressed nasal bridge, and small anteverted nose with long philtrum, as well as short feet and hands with sausage-like fingers. Death secondary to respiratory failure during the first few years of life was reported in the cases originally described but the outcome is now known to be highly variable with multiple long-term survivors. Typical radiographical features include short long bones with markedly delayed epiphyseal mineralization, metaphyseal cupping, short metacarpals and phalanges, and severe platyspondyly. Mutations in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1) are found in several families with OPS. However, not all patients have INPPL1 variants suggesting that OPS exhibits genetic heterogeneity.

MalaCards based summary : Opsismodysplasia, also known as opsmd, is related to rickets and hypophosphatemic rickets, x-linked recessive. An important gene associated with Opsismodysplasia is INPPL1 (Inositol Polyphosphate Phosphatase Like 1). Affiliated tissues include bone, and related phenotypes are macrocephaly and frontal bossing

NIH Rare Diseases : 53 Opsismodysplasia is a rare skeletal dysplasia characterized by congenital short stature and characteristic craniofacial abnormalities. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel (the space between the front bones of the skull), and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Children with opsismodysplasia are at an increased risk for respiratory infections and respiratory failure. This condition is caused by mutations in the INPPL1 the gene. It is inherited in an autosomal recessive manner.

OMIM : 57 Opsismodysplasia is a rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death in utero or secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges (summary by Below et al., 2013 and Fradet and Fitzgerald, 2017). (258480)

UniProtKB/Swiss-Prot : 74 Opsismodysplasia: A rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with very delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges.

Wikipedia : 75 Opsismodysplasia is a type of skeletal dysplasia (a bone disease that interferes with bone development)... more...

Related Diseases for Opsismodysplasia

Graphical network of the top 20 diseases related to Opsismodysplasia:



Diseases related to Opsismodysplasia

Symptoms & Phenotypes for Opsismodysplasia

Human phenotypes related to Opsismodysplasia:

59 32 (show all 49)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 frontal bossing 59 32 hallmark (90%) Very frequent (99-80%) HP:0002007
3 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
4 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
5 delayed skeletal maturation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002750
6 depressed nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0005280
7 short nose 59 32 hallmark (90%) Very frequent (99-80%) HP:0003196
8 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
9 brachydactyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001156
10 severe short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003510
11 large fontanelles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000239
12 tapered finger 59 32 hallmark (90%) Very frequent (99-80%) HP:0001182
13 hypoplastic pubic bone 59 32 hallmark (90%) Very frequent (99-80%) HP:0003173
14 hypoplastic ischia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003175
15 squared iliac bones 59 32 hallmark (90%) Very frequent (99-80%) HP:0003177
16 hypoplastic vertebral bodies 59 32 hallmark (90%) Very frequent (99-80%) HP:0008479
17 abnormally ossified vertebrae 32 hallmark (90%) HP:0100569
18 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
19 recurrent respiratory infections 59 32 frequent (33%) Frequent (79-30%) HP:0002205
20 flat occiput 59 32 frequent (33%) Frequent (79-30%) HP:0005469
21 pectus excavatum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000767
22 splenomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001744
23 hepatomegaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0002240
24 joint stiffness 59 32 occasional (7.5%) Occasional (29-5%) HP:0001387
25 broad thumb 59 32 occasional (7.5%) Occasional (29-5%) HP:0011304
26 narrow chest 59 32 occasional (7.5%) Occasional (29-5%) HP:0000774
27 blue sclerae 59 32 occasional (7.5%) Occasional (29-5%) HP:0000592
28 hypophosphatemia 32 occasional (7.5%) HP:0002148
29 renal phosphate wasting 32 occasional (7.5%) HP:0000117
30 hypertelorism 32 HP:0000316
31 short neck 32 HP:0000470
32 anteverted nares 32 HP:0000463
33 long philtrum 32 HP:0000343
34 generalized hypotonia 32 HP:0001290
35 edema 32 HP:0000969
36 short palm 32 HP:0004279
37 short long bone 32 HP:0003026
38 short foot 32 HP:0001773
39 rhizomelia 32 HP:0008905
40 polyhydramnios 32 HP:0001561
41 disproportionate short-limb short stature 32 HP:0008873
42 flat acetabular roof 32 HP:0003180
43 abnormal vertebral ossification 59 Very frequent (99-80%)
44 bell-shaped thorax 32 HP:0001591
45 anterior rib cupping 32 HP:0000907
46 protuberant abdomen 32 HP:0001538
47 metaphyseal cupping 32 HP:0003021
48 severe platyspondyly 32 HP:0004565
49 posterior rib cupping 32 HP:0000922

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
large fontanelles

Head And Neck Neck:
short neck
nuchal edema

Head And Neck Nose:
short nose
anteverted nostrils
flattened nasal bridge

Skeletal Pelvis:
hypoplastic ischia
hypoplastic pubis
horizontal acetabular roof
square iliac bones
medial and lateral spurs

Chest External Features:
bell-shaped thorax
narrow thorax

Skeletal Hands:
metaphyseal cupping
short hands
very short tubular bones

Neurologic Central Nervous System:
hypotonia

Abdomen External Features:
prominent abdomen

Respiratory:
susceptibility to respiratory infections

Genitourinary Kidneys:
renal phosphate wasting (in some patients)

Head And Neck Eyes:
hypertelorism

Head And Neck Face:
frontal bossing
long philtrum

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skeletal Skull:
hypoplastic vertebral bodies
severe platyspondyly

Skeletal Limbs:
metaphyseal cupping
rhizomelic shortening
very short long bones
marked delay in epiphyseal appearance

Skeletal Feet:
metaphyseal cupping
short feet
very short tubular bones

Skeletal Spine:
severe scoliosis

Growth Height:
dwarfism, identifiable at birth

Chest Ribs Sternum Clavicles And Scapulae:
anterior and posterior rib flaring
rib cupping

Metabolic Features:
hypophosphatemia (in some patients)

Clinical features from OMIM:

258480

Drugs & Therapeutics for Opsismodysplasia

Search Clinical Trials , NIH Clinical Center for Opsismodysplasia

Genetic Tests for Opsismodysplasia

Genetic tests related to Opsismodysplasia:

# Genetic test Affiliating Genes
1 Opsismodysplasia 29 INPPL1

Anatomical Context for Opsismodysplasia

MalaCards organs/tissues related to Opsismodysplasia:

41
Bone

Publications for Opsismodysplasia

Articles related to Opsismodysplasia:

(show all 24)
# Title Authors PMID Year
1
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. 38 8 71
23273567 2013
2
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. 38 8 71
23273569 2013
3
INPPL1 gene mutations in opsismodysplasia. 38 8
27708270 2017
4
Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. 38 8
27233067 2016
5
Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. 38 8
12624139 2003
6
Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal recessive inheritance. 38 8
10076884 1999
7
Opsismodysplasia: another case and literature review. 38 8
7551158 1995
8
Additional case of opsismodysplasia supporting autosomal recessive inheritance. 38 8
8209898 1994
9
Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae. 38 8
6496568 1984
10
A second locus for Schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1). 8
25997753 2015
11
Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. 8
17952091 2007
12
Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects. 38
28869677 2017
13
SHIP2: Structure, Function and Inhibition. 38
27907247 2017
14
Opsismodysplasia: Phosphate Wasting Osteodystrophy Responds to Bisphosphonate Therapy. 38
26157786 2015
15
Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1. 38
24953221 2014
16
SHIP2 signaling in normal and pathological situations: Its impact on cell proliferation. 38
24091101 2014
17
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. 38
23552673 2013
18
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. 38
23464704 2013
19
Opsismodysplasia. 38
20422326 2010
20
Atlanto-axial segmentation defects and os odontoideum in two male siblings with opsismodysplasia. 38
19050869 2009
21
Hypophosphatemic rickets in opsismodysplasia. 38
17315533 2007
22
A further case of opsismodysplasia with hydrocephalus. 38
16473316 2006
23
[Opsismodysplasia]. 38
11528795 2001
24
Opsismodysplasia: a case report. 38
9125065 1997

Variations for Opsismodysplasia

ClinVar genetic disease variations for Opsismodysplasia:

6 (show all 18)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 INPPL1 NM_001567.4(INPPL1): c.1976C> T (p.Pro659Leu) single nucleotide variant Pathogenic rs397514508 11:71944143-71944143 11:72233099-72233099
2 INPPL1 NM_001567.4(INPPL1): c.545C> A (p.Ser182Ter) single nucleotide variant Pathogenic rs397514509 11:71940160-71940160 11:72229116-72229116
3 INPPL1 NM_001567.4(INPPL1): c.768del (p.Glu258fs) deletion Pathogenic rs797044468 11:71940721-71940721 11:72229677-72229677
4 INPPL1 NM_001567.4(INPPL1): c.2415+1G> A single nucleotide variant Pathogenic rs655423 11:71945660-71945660 11:72234616-72234616
5 INPPL1 NM_001567.4(INPPL1): c.1975C> T (p.Pro659Ser) single nucleotide variant Pathogenic rs397514510 11:71944142-71944142 11:72233098-72233098
6 INPPL1 NM_001567.4(INPPL1): c.278_282del (p.Gln93fs) deletion Pathogenic rs797044469 11:71939423-71939427 11:72228379-72228383
7 INPPL1 NM_001567.4(INPPL1): c.1201C> T (p.Arg401Trp) single nucleotide variant Pathogenic rs397514511 11:71941843-71941843 11:72230799-72230799
8 INPPL1 NM_001567.4(INPPL1): c.2164T> A (p.Phe722Ile) single nucleotide variant Pathogenic rs397514512 11:71944740-71944740 11:72233696-72233696
9 INPPL1 NM_001567.4(INPPL1): c.94_121del (p.Glu32fs) deletion Pathogenic rs797044470 11:71936122-71936149 11:72225078-72225105
10 INPPL1 NM_001567.4(INPPL1): c.1845dup (p.Ile616fs) duplication Pathogenic rs1135401750 11:71943802-71943802 11:72232758-72232758
11 INPPL1 NM_001567.4(INPPL1): c.768_769del (p.Glu258fs) deletion Pathogenic rs746647683 11:71940721-71940722 11:72229677-72229678
12 INPPL1 NM_001567.4(INPPL1): c.2071C> T (p.Arg691Trp) single nucleotide variant Pathogenic rs878853123 11:71944515-71944515 11:72233471-72233471
13 INPPL1 NM_001567.4(INPPL1): c.1108_1155del (p.Ser370_Lys385del) deletion Uncertain significance 11:71941423-71941470 11:72230379-72230426
14 INPPL1 NM_001567.4(INPPL1): c.1636G> A (p.Val546Ile) single nucleotide variant Uncertain significance rs376117918 11:71943304-71943304 11:72232260-72232260
15 INPPL1 NM_001567.4(INPPL1): c.1682_1686ACCTC[1] (p.Thr563fs) short repeat no interpretation for the single variant rs878853121 11:71943355-71943359 11:72232311-72232315
16 INPPL1 NM_001567.4(INPPL1): c.24_39del (p.Gly9fs) deletion no interpretation for the single variant rs878853119 11:71936052-71936067 11:72225008-72225023
17 INPPL1 NM_001567.4(INPPL1): c.35dup (p.Ala13fs) duplication no interpretation for the single variant rs878853122 11:71936063-71936063 11:72225019-72225019
18 INPPL1 NM_001567.4(INPPL1): c.753G> C (p.Gln251His) single nucleotide variant no interpretation for the single variant rs878853120 11:71940602-71940602 11:72229558-72229558

UniProtKB/Swiss-Prot genetic disease variations for Opsismodysplasia:

74
# Symbol AA change Variation ID SNP ID
1 INPPL1 p.Arg401Trp VAR_069586 rs397514511
2 INPPL1 p.Pro659Ser VAR_069587 rs397514510
3 INPPL1 p.Trp688Cys VAR_069588
4 INPPL1 p.Phe722Ile VAR_069589 rs397514512

Expression for Opsismodysplasia

Search GEO for disease gene expression data for Opsismodysplasia.

Pathways for Opsismodysplasia

GO Terms for Opsismodysplasia

Biological processes related to Opsismodysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to vitamin D GO:0071305 9.16 PHEX FGF23
2 cellular response to parathyroid hormone stimulus GO:0071374 8.96 PHEX FGF23
3 response to sodium phosphate GO:1904383 8.62 PHEX FGF23

Sources for Opsismodysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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