OPSMD
MCID: OPS002
MIFTS: 34

Opsismodysplasia (OPSMD)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Respiratory diseases, Smell/Taste diseases
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Aliases & Classifications for Opsismodysplasia

MalaCards integrated aliases for Opsismodysplasia:

Name: Opsismodysplasia 57 19 58 75 73 28 5 38 71
Opsmd 57 73

Characteristics:


Inheritance:

Autosomal recessive 58 57

Prevelance:

<1/1000000 (Worldwide) 58

Age Of Onset:

Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
may result in death in neonatal period or early childhood


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Opsismodysplasia

OMIM®: 57 Opsismodysplasia (OPSMD) 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 08-Dec-2022)

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

GARD: 19 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 genetic changes in the INPPL1 the gene. It is inherited in an autosomal recessive manner.

UniProtKB/Swiss-Prot: 73 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.

Orphanet: 58 Opsismodysplasia is a skeletal dysplasia characterized by congenital dwarfism and facial dysmorphism.

Wikipedia: 75 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:

# Related Disease Score Top Affiliating Genes
1 osteochondrodysplasia 10.3
2 bone disease 10.1
3 hydrocephalus, congenital, 1 9.9
4 ataxia with vitamin e deficiency 9.9
5 hypophosphatemic rickets, x-linked recessive 9.9
6 hypophosphatemia 9.9
7 rickets 9.9
8 hydrocephalus 9.9
9 polyhydramnios 9.9
10 spondylodysplastic dysplasia 9.9

Graphical network of the top 20 diseases related to Opsismodysplasia:



Diseases related to Opsismodysplasia

Symptoms & Phenotypes for Opsismodysplasia

Human phenotypes related to Opsismodysplasia:

58 30 (show top 50) (show all 62)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000256
2 frontal bossing 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002007
3 respiratory insufficiency 58 30 Very rare (1%) Very frequent (99-80%)
HP:0002093
4 delayed skeletal maturation 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002750
5 depressed nasal bridge 58 30 Very rare (1%) Very frequent (99-80%)
HP:0005280
6 short nose 58 30 Very rare (1%) Very frequent (99-80%)
HP:0003196
7 brachydactyly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001156
8 large fontanelles 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000239
9 abnormally ossified vertebrae 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0100569
10 tapered finger 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001182
11 severe short stature 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003510
12 hypoplastic pubic bone 58 30 Very rare (1%) Very frequent (99-80%)
HP:0003173
13 hypoplastic ischia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0003175
14 squared iliac bones 58 30 Very rare (1%) Very frequent (99-80%)
HP:0003177
15 hypoplastic vertebral bodies 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0008479
16 abnormal epiphysis morphology 30 Hallmark (90%) HP:0005930
17 abnormal metaphysis morphology 30 Hallmark (90%) HP:0000944
18 hypotonia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001252
19 recurrent respiratory infections 58 30 Frequent (33%) Frequent (79-30%)
HP:0002205
20 flat occiput 58 30 Frequent (33%) Frequent (79-30%)
HP:0005469
21 splenomegaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001744
22 hepatomegaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002240
23 joint stiffness 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001387
24 broad thumb 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011304
25 pectus excavatum 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000767
26 narrow chest 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000774
27 blue sclerae 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000592
28 hypertelorism 30 Very rare (1%) HP:0000316
29 hypophosphatemia 30 Very rare (1%) HP:0002148
30 prominent forehead 30 Very rare (1%) HP:0011220
31 low-set ears 30 Very rare (1%) HP:0000369
32 motor delay 30 Very rare (1%) HP:0001270
33 high forehead 30 Very rare (1%) HP:0000348
34 short metacarpal 30 Very rare (1%) HP:0010049
35 short foot 30 Very rare (1%) HP:0001773
36 oligohydramnios 30 Very rare (1%) HP:0001562
37 short palm 30 Very rare (1%) HP:0004279
38 posteriorly rotated ears 30 Very rare (1%) HP:0000358
39 short phalanx of finger 30 Very rare (1%) HP:0009803
40 long palpebral fissure 30 Very rare (1%) HP:0000637
41 metaphyseal cupping 30 Very rare (1%) HP:0003021
42 hypoplasia of the odontoid process 30 Very rare (1%) HP:0003311
43 soft, doughy skin 30 Very rare (1%) HP:0001027
44 small foramen magnum 30 Very rare (1%) HP:0002677
45 shallow orbits 30 Very rare (1%) HP:0000586
46 renal phosphate wasting 30 Very rare (1%) HP:0000117
47 scoliosis 30 HP:0002650
48 short neck 30 HP:0000470
49 anteverted nares 30 HP:0000463
50 abnormality of the metaphysis 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Head:
macrocephaly
large fontanelles

Head And Neck Neck:
short neck
nuchal edema

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

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

Neurologic Central Nervous System:
hypotonia

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

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 08-Dec-2022)

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 28 INPPL1

Anatomical Context for Opsismodysplasia

Organs/tissues related to Opsismodysplasia:

MalaCards : Bone, Skin

Publications for Opsismodysplasia

Articles related to Opsismodysplasia:

(show all 26)
# Title Authors PMID Year
1
INPPL1 gene mutations in opsismodysplasia. 62 57 5
27708270 2017
2
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. 62 57 5
23273569 2013
3
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. 62 57 5
23273567 2013
4
A second locus for Schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1). 57 5
25997753 2015
5
Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. 57 5
17952091 2007
6
Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. 62 57
27233067 2016
7
Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. 62 57
12624139 2003
8
Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal recessive inheritance. 62 57
10076884 1999
9
Opsismodysplasia: another case and literature review. 62 57
7551158 1995
10
Additional case of opsismodysplasia supporting autosomal recessive inheritance. 62 57
8209898 1994
11
Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae. 62 57
6496568 1984
12
Altered chondrocyte differentiation, matrix mineralization and MEK-Erk1/2 signaling in an INPPL1 catalytic knock-out mouse model of opsismodysplasia. 62
31519471 2020
13
Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update. 62
31628071 2020
14
Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects. 62
28869677 2017
15
SHIP2: Structure, Function and Inhibition. 62
27907247 2017
16
Opsismodysplasia: Phosphate Wasting Osteodystrophy Responds to Bisphosphonate Therapy. 62
26157786 2015
17
Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1. 62
24953221 2014
18
SHIP2 signaling in normal and pathological situations: Its impact on cell proliferation. 62
24091101 2014
19
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. 62
23464704 2013
20
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. 62
23552673 2013
21
Opsismodysplasia. 62
20422326 2010
22
Atlanto-axial segmentation defects and os odontoideum in two male siblings with opsismodysplasia. 62
19050869 2009
23
Hypophosphatemic rickets in opsismodysplasia. 62
17315533 2007
24
A further case of opsismodysplasia with hydrocephalus. 62
16473316 2006
25
[Opsismodysplasia]. 62
11528795 2001
26
Opsismodysplasia: a case report. 62
9125065 1997

Variations for Opsismodysplasia

ClinVar genetic disease variations for Opsismodysplasia:

5 (show all 32)
# 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) DEL 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.278_282del (p.Gln93fs) DEL Pathogenic
39478 rs797044469 GRCh37: 11:71939421-71939425
GRCh38: 11:72228377-72228381
6 INPPL1 NM_001567.4(INPPL1):c.1201C>T (p.Arg401Trp) SNV Pathogenic
39479 rs397514511 GRCh37: 11:71941843-71941843
GRCh38: 11:72230799-72230799
7 INPPL1 NM_001567.4(INPPL1):c.2164T>A (p.Phe722Ile) SNV Pathogenic
39480 rs397514512 GRCh37: 11:71944740-71944740
GRCh38: 11:72233696-72233696
8 INPPL1 NM_001567.4(INPPL1):c.94_121del (p.Glu32fs) DEL Pathogenic
39481 rs797044470 GRCh37: 11:71936115-71936142
GRCh38: 11:72225071-72225098
9 INPPL1 NM_001567.4(INPPL1):c.2071C>T (p.Arg691Trp) SNV Pathogenic
235826 rs878853123 GRCh37: 11:71944515-71944515
GRCh38: 11:72233471-72233471
10 INPPL1 NM_001567.4(INPPL1):c.768_769del (p.Glu258fs) DEL Pathogenic
235824 rs746647683 GRCh37: 11:71940721-71940722
GRCh38: 11:72229677-72229678
11 INPPL1 NM_001567.4(INPPL1):c.35dup (p.Ala13fs) DUP Pathogenic
235823 rs878853122 GRCh37: 11:71936057-71936058
GRCh38: 11:72225013-72225014
12 INPPL1 NM_001567.4(INPPL1):c.2415+1G>A SNV Pathogenic
235825 rs655423 GRCh37: 11:71945660-71945660
GRCh38: 11:72234616-72234616
13 INPPL1 NM_001567.4(INPPL1):c.1115del (p.Arg372fs) DEL Pathogenic
431059 rs1135401751 GRCh37: 11:71941430-71941430
GRCh38: 11:72230386-72230386
14 INPPL1 NM_001567.4(INPPL1):c.1845dup (p.Ile616fs) DUP Pathogenic
431058 rs1135401750 GRCh37: 11:71943801-71943802
GRCh38: 11:72232757-72232758
15 INPPL1 NM_001567.4(INPPL1):c.939+1G>A SNV Pathogenic
931442 rs1948786646 GRCh37: 11:71941064-71941064
GRCh38: 11:72230020-72230020
16 INPPL1 NM_001567.4(INPPL1):c.306C>G (p.Tyr102Ter) SNV Pathogenic
1323117 GRCh37: 11:71939451-71939451
GRCh38: 11:72228407-72228407
17 INPPL1 NM_001567.4(INPPL1):c.3551_3552+1del MICROSAT Pathogenic
1323118 GRCh37: 11:71948835-71948837
GRCh38: 11:72237791-72237793
18 INPPL1 NM_001567.4(INPPL1):c.24_39del (p.Gly9fs) DEL Pathogenic
235822 rs878853119 GRCh37: 11:71936044-71936059
GRCh38: 11:72225000-72225015
19 INPPL1 NM_001567.4(INPPL1):c.1975C>T (p.Pro659Ser) SNV Pathogenic
39477 rs397514510 GRCh37: 11:71944142-71944142
GRCh38: 11:72233098-72233098
20 INPPL1 NM_001567.4(INPPL1):c.3562dup (p.Leu1188fs) DUP Pathogenic
1709919 GRCh37: 11:71949093-71949094
GRCh38: 11:72238049-72238050
21 INPPL1 NM_001567.4(INPPL1):c.115_128del (p.Gly39fs) DEL Likely Pathogenic
1683469 GRCh37: 11:71936142-71936155
GRCh38: 11:72225098-72225111
22 INPPL1 NM_001567.4(INPPL1):c.2356C>T (p.Gln786Ter) SNV Likely Pathogenic
1324584 GRCh37: 11:71945600-71945600
GRCh38: 11:72234556-72234556
23 INPPL1 NM_001567.4(INPPL1):c.24_39del (p.Gly9fs) DEL Likely Pathogenic
242401 rs878853119 GRCh37: 11:71936044-71936059
GRCh38: 11:72225000-72225015
24 INPPL1 NM_001567.4(INPPL1):c.3466del (p.Arg1156fs) DEL Likely Pathogenic
1339494 GRCh37: 11:71948748-71948748
GRCh38: 11:72237704-72237704
25 INPPL1 NM_001567.4(INPPL1):c.2213-2A>C SNV Likely Pathogenic
1027944 rs1948918434 GRCh37: 11:71945323-71945323
GRCh38: 11:72234279-72234279
26 INPPL1 NM_001567.4(INPPL1):c.3549_3550insA (p.Glu1184fs) INSERT Likely Pathogenic
1029357 rs1949036008 GRCh37: 11:71948837-71948838
GRCh38: 11:72237793-72237794
27 INPPL1 NM_001567.4(INPPL1):c.2326+9C>T SNV Uncertain Significance
1032754 rs370540380 GRCh37: 11:71945447-71945447
GRCh38: 11:72234403-72234403
28 INPPL1 NM_001567.4(INPPL1):c.1963A>T (p.Ile655Phe) SNV Uncertain Significance
1683468 GRCh37: 11:71944130-71944130
GRCh38: 11:72233086-72233086
29 INPPL1 NM_001567.4(INPPL1):c.1108_1155del (p.Ser370_Lys385del) DEL Uncertain Significance
590925 rs1565388201 GRCh37: 11:71941420-71941467
GRCh38: 11:72230376-72230423
30 INPPL1 NM_001567.4(INPPL1):c.1636G>A (p.Val546Ile) SNV Uncertain Significance
488146 rs376117918 GRCh37: 11:71943304-71943304
GRCh38: 11:72232260-72232260
31 INPPL1 NM_001567.4(INPPL1):c.987A>G (p.Ser329=) SNV Benign
1170422 GRCh37: 11:71941212-71941212
GRCh38: 11:72230168-72230168
32 INPPL1 NM_001567.4(INPPL1):c.1091-25A>G SNV Benign
1289494 GRCh37: 11:71941381-71941381
GRCh38: 11:72230337-72230337

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

Sources for Opsismodysplasia

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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