OPSMD
MCID: OPS002
MIFTS: 37

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 56 74 52 58 73 36 29 13 6 39 71
Opsmd 56 73

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
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 delayed skeletal maturation and depressed nasal bridge

NIH Rare Diseases : 52 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 : 56 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 : 73 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 : 74 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 35)
# Related Disease Score Top Affiliating Genes
1 rickets 29.9 PHEX FGF23
2 hypophosphatemic rickets, x-linked recessive 29.8 PHEX FGF23
3 hypophosphatemia 29.6 PHEX FGF23
4 odontochondrodysplasia 29.3 PHEX FGF23
5 hydrocephalus 10.2
6 polyhydramnios 10.2
7 skeletal dysplasias 10.2
8 spondylodysplastic dysplasia 10.2
9 oncogenic osteomalacia 9.8 PHEX FGF23
10 osteomalacia 9.8 PHEX FGF23
11 dental abscess 9.8 PHEX FGF23
12 familial tumoral calcinosis 9.8 PHEX FGF23
13 calcinosis 9.8 PHEX FGF23
14 hypophosphatemic rickets with hypercalciuria, hereditary 9.7 PHEX FGF23
15 enthesopathy 9.7 PHEX FGF23
16 hypophosphatemic rickets, x-linked dominant 9.7 PHEX FGF23
17 metaphyseal chondrodysplasia, jansen type 9.7 PHEX FGF23
18 hypophosphatemic rickets, autosomal dominant 9.7 PHEX FGF23
19 osteoglophonic dysplasia 9.7 PHEX FGF23
20 autosomal recessive hypophosphatemic rickets 9.7 PHEX FGF23
21 phosphorus metabolism disease 9.7 PHEX FGF23
22 arterial calcification of infancy 9.7 PHEX FGF23
23 hypophosphatasia 9.7 PHEX FGF23
24 schimmelpenning-feuerstein-mims syndrome 9.7 PHEX FGF23
25 parathyroid gland disease 9.7 PHEX FGF23
26 tumoral calcinosis, hyperphosphatemic, familial, 1 9.7 PHEX FGF23
27 nevus, epidermal 9.7 PHEX FGF23
28 mineral metabolism disease 9.6 PHEX FGF23
29 hyperphosphatemia 9.6 PHEX FGF23
30 fanconi syndrome 9.6 PHEX FGF23
31 secondary hyperparathyroidism 9.6 PHEX FGF23
32 hyperparathyroidism 9.6 PHEX FGF23
33 bone remodeling disease 9.5 PHEX FGF23
34 nephrocalcinosis 9.5 PHEX FGF23
35 bone disease 9.2 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 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
2 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
3 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
4 short nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003196
5 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
6 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
7 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
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 tapered finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0001182
12 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
13 hypoplastic pubic bone 58 31 hallmark (90%) Very frequent (99-80%) HP:0003173
14 hypoplastic ischia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003175
15 squared iliac bones 58 31 hallmark (90%) Very frequent (99-80%) HP:0003177
16 hypoplastic vertebral bodies 58 31 hallmark (90%) Very frequent (99-80%) HP:0008479
17 abnormally ossified vertebrae 31 hallmark (90%) HP:0100569
18 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
19 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
20 flat occiput 58 31 frequent (33%) Frequent (79-30%) HP:0005469
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 hypertelorism 31 HP:0000316
31 short neck 31 HP:0000470
32 scoliosis 31 HP:0002650
33 anteverted nares 31 HP:0000463
34 edema 31 HP:0000969
35 polyhydramnios 31 HP:0001561
36 long philtrum 31 HP:0000343
37 abnormal vertebral ossification 58 Very frequent (99-80%)
38 short foot 31 HP:0001773
39 disproportionate short-limb short stature 31 HP:0008873
40 short palm 31 HP:0004279
41 rhizomelia 31 HP:0008905
42 protuberant abdomen 31 HP:0001538
43 generalized hypotonia 31 HP:0001290
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:

56
Head And Neck Eyes:
hypertelorism

Head And Neck Head:
macrocephaly
large fontanelles

Head And Neck Face:
frontal bossing
long philtrum

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 Neck:
short neck
nuchal edema

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

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

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. 56 6 61
27708270 2017
2
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. 56 6 61
23273567 2013
3
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. 61 6 56
23273569 2013
4
A second locus for Schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1). 56 6
25997753 2015
5
Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. 6 56
17952091 2007
6
Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. 56 61
27233067 2016
7
Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. 61 56
12624139 2003
8
Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal recessive inheritance. 56 61
10076884 1999
9
Opsismodysplasia: another case and literature review. 61 56
7551158 1995
10
Additional case of opsismodysplasia supporting autosomal recessive inheritance. 61 56
8209898 1994
11
Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae. 61 56
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
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. 61
23464704 2013
20
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. 61
23552673 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 18) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 INPPL1 NM_001567.4(INPPL1):c.1976C>T (p.Pro659Leu)SNV Pathogenic 39473 rs397514508 11:71944143-71944143 11:72233099-72233099
2 INPPL1 NM_001567.4(INPPL1):c.545C>A (p.Ser182Ter)SNV Pathogenic 39474 rs397514509 11:71940160-71940160 11:72229116-72229116
3 INPPL1 NM_001567.4(INPPL1):c.768del (p.Glu258fs)deletion Pathogenic 39475 rs797044468 11:71940721-71940721 11:72229677-72229677
4 INPPL1 NM_001567.4(INPPL1):c.2415+1G>ASNV Pathogenic 39476 rs655423 11:71945660-71945660 11:72234616-72234616
5 INPPL1 NM_001567.4(INPPL1):c.1975C>T (p.Pro659Ser)SNV Pathogenic 39477 rs397514510 11:71944142-71944142 11:72233098-72233098
6 INPPL1 NM_001567.4(INPPL1):c.278_282del (p.Gln93fs)deletion Pathogenic 39478 rs797044469 11:71939421-71939425 11:72228377-72228381
7 INPPL1 NM_001567.4(INPPL1):c.1201C>T (p.Arg401Trp)SNV Pathogenic 39479 rs397514511 11:71941843-71941843 11:72230799-72230799
8 INPPL1 NM_001567.4(INPPL1):c.2164T>A (p.Phe722Ile)SNV Pathogenic 39480 rs397514512 11:71944740-71944740 11:72233696-72233696
9 INPPL1 NM_001567.4(INPPL1):c.94_121del (p.Glu32fs)deletion Pathogenic 39481 rs797044470 11:71936115-71936142 11:72225071-72225098
10 INPPL1 NM_001567.4(INPPL1):c.1845dup (p.Ile616fs)duplication Pathogenic 431058 rs1135401750 11:71943801-71943802 11:72232757-72232758
11 INPPL1 NM_001567.4(INPPL1):c.768_769del (p.Glu258fs)deletion Pathogenic 235824 rs746647683 11:71940721-71940722 11:72229677-72229678
12 INPPL1 NM_001567.4(INPPL1):c.2071C>T (p.Arg691Trp)SNV Pathogenic 235826 rs878853123 11:71944515-71944515 11:72233471-72233471
13 INPPL1 NM_001567.4(INPPL1):c.1636G>A (p.Val546Ile)SNV Uncertain significance 488146 rs376117918 11:71943304-71943304 11:72232260-72232260
14 INPPL1 NM_001567.4(INPPL1):c.1108_1155del (p.Ser370_Lys385del)deletion Uncertain significance 590925 rs1565388201 11:71941420-71941467 11:72230376-72230423
15 INPPL1 NM_001567.4(INPPL1):c.1682_1686ACCTC[1] (p.Thr563fs)short repeat no interpretation for the single variant 242398 rs878853121 11:71943348-71943352 11:72232304-72232308
16 INPPL1 NM_001567.4(INPPL1):c.24_39del (p.Gly9fs)deletion no interpretation for the single variant 242401 rs878853119 11:71936044-71936059 11:72225000-72225015
17 INPPL1 NM_001567.4(INPPL1):c.35dup (p.Ala13fs)duplication no interpretation for the single variant 242400 rs878853122 11:71936057-71936058 11:72225013-72225014
18 INPPL1 NM_001567.4(INPPL1):c.753G>C (p.Gln251His)SNV no interpretation for the single variant 242399 rs878853120 11:71940602-71940602 11:72229558-72229558

UniProtKB/Swiss-Prot genetic disease variations for Opsismodysplasia:

73
# 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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....