OPSMD
MCID: OPS002
MIFTS: 38

Opsismodysplasia (OPSMD)

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

Aliases & Classifications for Opsismodysplasia

MalaCards integrated aliases for Opsismodysplasia:

Name: Opsismodysplasia 57 73 20 58 72 36 29 13 6 39 70
Opsmd 57 72

Characteristics:

Orphanet epidemiological data:

58
opsismodysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

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


HPO:

31
opsismodysplasia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Opsismodysplasia

KEGG : 36 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

GARD : 20 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) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 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 : 73 Opsismodysplasia is a type of skeletal dysplasia (a bone disease that interferes with bone development)... more...

Related Diseases for Opsismodysplasia

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

(show all 34)
# Related Disease Score Top Affiliating Genes
1 rickets 29.6 PHEX FGF23
2 hypophosphatemic rickets, x-linked recessive 29.5 PHEX FGF23
3 hypophosphatemia 29.4 PHEX FGF23
4 odontochondrodysplasia 29.2 PHEX FGF23
5 hydrocephalus, congenital, 1 9.9
6 hydrocephalus 9.9
7 polyhydramnios 9.9
8 skeletal dysplasias 9.9
9 spondylodysplastic dysplasia 9.9
10 oncogenic osteomalacia 9.8 PHEX FGF23
11 osteomalacia 9.8 PHEX FGF23
12 dental abscess 9.8 PHEX FGF23
13 hypophosphatemic rickets with hypercalciuria, hereditary 9.8 PHEX FGF23
14 familial tumoral calcinosis 9.8 PHEX FGF23
15 calcinosis 9.8 PHEX FGF23
16 enthesopathy 9.8 PHEX FGF23
17 metaphyseal chondrodysplasia, jansen type 9.8 PHEX FGF23
18 hypophosphatemic rickets, autosomal dominant 9.8 PHEX FGF23
19 osteoglophonic dysplasia 9.8 PHEX FGF23
20 phosphorus metabolism disease 9.8 PHEX FGF23
21 autosomal recessive hypophosphatemic rickets 9.8 PHEX FGF23
22 arterial calcification of infancy 9.8 PHEX FGF23
23 hypophosphatasia 9.8 PHEX FGF23
24 mineral metabolism disease 9.8 PHEX FGF23
25 tumoral calcinosis, hyperphosphatemic, familial, 1 9.8 PHEX FGF23
26 hyperphosphatemia 9.8 PHEX FGF23
27 schimmelpenning-feuerstein-mims syndrome 9.8 PHEX FGF23
28 nevus, epidermal 9.8 PHEX FGF23
29 secondary hyperparathyroidism 9.7 PHEX FGF23
30 hyperparathyroidism 9.7 PHEX FGF23
31 fanconi syndrome 9.7 PHEX FGF23
32 bone remodeling disease 9.7 PHEX FGF23
33 hypophosphatemic rickets, x-linked dominant 9.6 PHEX FGF23
34 bone disease 9.5 PHEX FGF23

Graphical network of the top 20 diseases related to Opsismodysplasia:



Diseases related to Opsismodysplasia

Symptoms & Phenotypes for Opsismodysplasia

Human phenotypes related to Opsismodysplasia:

58 31 (show all 50)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
3 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
4 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
5 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
6 short nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003196
7 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
8 brachydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001156
9 abnormality of epiphysis morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0005930
10 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%) HP:0000239
11 abnormally ossified vertebrae 58 31 hallmark (90%) Very frequent (99-80%) HP:0100569
12 tapered finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0001182
13 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
14 hypoplastic pubic bone 58 31 hallmark (90%) Very frequent (99-80%) HP:0003173
15 hypoplastic ischia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003175
16 squared iliac bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0003177
17 hypoplastic vertebral bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0008479
18 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
19 flat occiput 58 31 frequent (33%) Frequent (79-30%) HP:0005469
20 hypotonia 31 frequent (33%) HP:0001252
21 splenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001744
22 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
23 joint stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0001387
24 broad thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0011304
25 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
26 narrow chest 58 31 occasional (7.5%) Occasional (29-5%) HP:0000774
27 blue sclerae 58 31 occasional (7.5%) Occasional (29-5%) HP:0000592
28 hypophosphatemia 31 occasional (7.5%) HP:0002148
29 renal phosphate wasting 31 occasional (7.5%) HP:0000117
30 scoliosis 31 HP:0002650
31 short neck 31 HP:0000470
32 muscular hypotonia 58 Frequent (79-30%)
33 hypertelorism 31 HP:0000316
34 anteverted nares 31 HP:0000463
35 polyhydramnios 31 HP:0001561
36 long philtrum 31 HP:0000343
37 short foot 31 HP:0001773
38 disproportionate short-limb short stature 31 HP:0008873
39 short palm 31 HP:0004279
40 rhizomelia 31 HP:0008905
41 protuberant abdomen 31 HP:0001538
42 generalized hypotonia 31 HP:0001290
43 edema 31 HP:0000969
44 short long bone 31 HP:0003026
45 bell-shaped thorax 31 HP:0001591
46 anterior rib cupping 31 HP:0000907
47 flat acetabular roof 31 HP:0003180
48 metaphyseal cupping 31 HP:0003021
49 severe platyspondyly 31 HP:0004565
50 posterior rib cupping 31 HP:0000922

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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
short tubular bones

Neurologic Central Nervous System:
hypotonia

Abdomen External Features:
prominent abdomen

Respiratory:
respiratory infections, susceptibility to

Genitourinary Kidneys:
renal phosphate wasting (in some patients)

Head And Neck Face:
frontal bossing
long philtrum

Head And Neck Eyes:
hypertelorism

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skeletal Skull:
hypoplastic vertebral bodies
severe platyspondyly

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

Skeletal Feet:
metaphyseal cupping
short feet
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 (Updated 05-Apr-2021)

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:

40
Bone

Publications for Opsismodysplasia

Articles related to Opsismodysplasia:

(show all 26)
# Title Authors PMID Year
1
INPPL1 gene mutations in opsismodysplasia. 61 57 6
27708270 2017
2
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. 6 57 61
23273569 2013
3
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. 61 6 57
23273567 2013
4
A second locus for Schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1). 57 6
25997753 2015
5
Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. 57 6
17952091 2007
6
Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. 61 57
27233067 2016
7
Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. 57 61
12624139 2003
8
Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal recessive inheritance. 57 61
10076884 1999
9
Opsismodysplasia: another case and literature review. 57 61
7551158 1995
10
Additional case of opsismodysplasia supporting autosomal recessive inheritance. 57 61
8209898 1994
11
Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae. 57 61
6496568 1984
12
Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia. 61
31519471 2020
13
Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update. 61
31628071 2020
14
Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects. 61
28869677 2017
15
SHIP2: Structure, Function and Inhibition. 61
27907247 2017
16
Opsismodysplasia: Phosphate Wasting Osteodystrophy Responds to Bisphosphonate Therapy. 61
26157786 2015
17
Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1. 61
24953221 2014
18
SHIP2 signaling in normal and pathological situations: Its impact on cell proliferation. 61
24091101 2014
19
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. 61
23552673 2013
20
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. 61
23464704 2013
21
Opsismodysplasia. 61
20422326 2010
22
Atlanto-axial segmentation defects and os odontoideum in two male siblings with opsismodysplasia. 61
19050869 2009
23
Hypophosphatemic rickets in opsismodysplasia. 61
17315533 2007
24
A further case of opsismodysplasia with hydrocephalus. 61
16473316 2006
25
[Opsismodysplasia]. 61
11528795 2001
26
Opsismodysplasia: a case report. 61
9125065 1997

Variations for Opsismodysplasia

ClinVar genetic disease variations for Opsismodysplasia:

6 (show all 22)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 INPPL1 NM_001567.4(INPPL1):c.1976C>T (p.Pro659Leu) SNV Pathogenic 39473 rs397514508 GRCh37: 11:71944143-71944143
GRCh38: 11:72233099-72233099
2 INPPL1 NM_001567.4(INPPL1):c.545C>A (p.Ser182Ter) SNV Pathogenic 39474 rs397514509 GRCh37: 11:71940160-71940160
GRCh38: 11:72229116-72229116
3 INPPL1 NM_001567.4(INPPL1):c.768del (p.Glu258fs) Deletion Pathogenic 39475 rs797044468 GRCh37: 11:71940721-71940721
GRCh38: 11:72229677-72229677
4 INPPL1 NM_001567.4(INPPL1):c.2415+1G>A SNV Pathogenic 39476 rs655423 GRCh37: 11:71945660-71945660
GRCh38: 11:72234616-72234616
5 INPPL1 NM_001567.4(INPPL1):c.1975C>T (p.Pro659Ser) SNV Pathogenic 39477 rs397514510 GRCh37: 11:71944142-71944142
GRCh38: 11:72233098-72233098
6 INPPL1 NM_001567.4(INPPL1):c.278_282del (p.Gln93fs) Deletion Pathogenic 39478 rs797044469 GRCh37: 11:71939421-71939425
GRCh38: 11:72228377-72228381
7 INPPL1 NM_001567.4(INPPL1):c.1201C>T (p.Arg401Trp) SNV Pathogenic 39479 rs397514511 GRCh37: 11:71941843-71941843
GRCh38: 11:72230799-72230799
8 INPPL1 NM_001567.4(INPPL1):c.2164T>A (p.Phe722Ile) SNV Pathogenic 39480 rs397514512 GRCh37: 11:71944740-71944740
GRCh38: 11:72233696-72233696
9 INPPL1 NM_001567.4(INPPL1):c.94_121del (p.Glu32fs) Deletion Pathogenic 39481 rs797044470 GRCh37: 11:71936115-71936142
GRCh38: 11:72225071-72225098
10 INPPL1 NM_001567.4(INPPL1):c.24_39del (p.Gly9fs) Deletion Pathogenic 235822 rs878853119 GRCh37: 11:71936044-71936059
GRCh38: 11:72225000-72225015
11 INPPL1 NM_001567.4(INPPL1):c.2071C>T (p.Arg691Trp) SNV Pathogenic 235826 rs878853123 GRCh37: 11:71944515-71944515
GRCh38: 11:72233471-72233471
12 INPPL1 NM_001567.4(INPPL1):c.768_769del (p.Glu258fs) Deletion Pathogenic 235824 rs746647683 GRCh37: 11:71940721-71940722
GRCh38: 11:72229677-72229678
13 INPPL1 NM_001567.4(INPPL1):c.35dup (p.Ala13fs) Duplication Pathogenic 235823 rs878853122 GRCh37: 11:71936057-71936058
GRCh38: 11:72225013-72225014
14 INPPL1 NM_001567.4(INPPL1):c.2415+1G>A SNV Pathogenic 235825 rs655423 GRCh37: 11:71945660-71945660
GRCh38: 11:72234616-72234616
15 INPPL1 NM_001567.4(INPPL1):c.1115del (p.Arg372fs) Deletion Pathogenic 431059 rs1135401751 GRCh37: 11:71941430-71941430
GRCh38: 11:72230386-72230386
16 INPPL1 NM_001567.4(INPPL1):c.1845dup (p.Ile616fs) Duplication Pathogenic 431058 rs1135401750 GRCh37: 11:71943801-71943802
GRCh38: 11:72232757-72232758
17 INPPL1 NM_001567.4(INPPL1):c.939+1G>A SNV Pathogenic 931442 GRCh37: 11:71941064-71941064
GRCh38: 11:72230020-72230020
18 INPPL1 NM_001567.4(INPPL1):c.2213-2A>C SNV Likely pathogenic 1027944 GRCh37: 11:71945323-71945323
GRCh38: 11:72234279-72234279
19 INPPL1 NM_001567.4(INPPL1):c.3549_3550insA (p.Glu1184fs) Insertion Likely pathogenic 1029357 GRCh37: 11:71948837-71948838
GRCh38: 11:72237793-72237794
20 INPPL1 NM_001567.4(INPPL1):c.2326+9C>T SNV Uncertain significance 1032754 GRCh37: 11:71945447-71945447
GRCh38: 11:72234403-72234403
21 INPPL1 NM_001567.4(INPPL1):c.1636G>A (p.Val546Ile) SNV Uncertain significance 488146 rs376117918 GRCh37: 11:71943304-71943304
GRCh38: 11:72232260-72232260
22 INPPL1 NM_001567.4(INPPL1):c.1108_1155del (p.Ser370_Lys385del) Deletion Uncertain significance 590925 rs1565388201 GRCh37: 11:71941420-71941467
GRCh38: 11:72230376-72230423

UniProtKB/Swiss-Prot genetic disease variations for Opsismodysplasia:

72
# 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
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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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