MCID: OPS002
MIFTS: 38

Opsismodysplasia

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Opsismodysplasia

MalaCards integrated aliases for Opsismodysplasia:

Name: Opsismodysplasia 57 76 53 59 75 37 29 13 6 40 73
Opsmd 57 75

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:



Summaries for Opsismodysplasia

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 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 (summary by Below et al., 2013). (258480)

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

NIH Rare Diseases : 53 Opsismodysplasia is a rare skeletal dysplasia characterized by congenitalshort 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.

UniProtKB/Swiss-Prot : 75 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 : 76 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

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

Human phenotypes related to Opsismodysplasia:

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

MGI Mouse Phenotypes related to Opsismodysplasia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.33 INPPL1 PHEX SH3PXD2B
2 growth/size/body region MP:0005378 9.26 SH3PXD2B FGF23 INPPL1 PHEX
3 limbs/digits/tail MP:0005371 8.8 FGF23 PHEX SH3PXD2B

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 19)
# Title Authors Year
1
INPPL1 gene mutations in opsismodysplasia. ( 27708270 )
2017
2
Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects. ( 28869677 )
2017
3
Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. ( 27233067 )
2016
4
Opsismodysplasia: Phosphate Wasting Osteodystrophy Responds to Bisphosphonate Therapy. ( 26157786 )
2015
5
Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1. ( 24953221 )
2014
6
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. ( 23273569 )
2013
7
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. ( 23552673 )
2013
8
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. ( 23273567 )
2013
9
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. ( 23464704 )
2013
10
Opsismodysplasia. ( 20422326 )
2010
11
Atlanto-axial segmentation defects and os odontoideum in two male siblings with opsismodysplasia. ( 19050869 )
2009
12
Hypophosphatemic rickets in opsismodysplasia. ( 17315533 )
2007
13
A further case of opsismodysplasia with hydrocephalus. ( 16473316 )
2006
14
Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. ( 12624139 )
2003
15
Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal recessive inheritance. ( 10076884 )
1999
16
Opsismodysplasia: a case report. ( 9125065 )
1997
17
Opsismodysplasia: another case and literature review. ( 7551158 )
1995
18
Additional case of opsismodysplasia supporting autosomal recessive inheritance. ( 8209898 )
1994
19
Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the hand and the vertebrae. ( 6496568 )
1984

Variations for Opsismodysplasia

UniProtKB/Swiss-Prot genetic disease variations for Opsismodysplasia:

75
# 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

ClinVar genetic disease variations for Opsismodysplasia:

6
(show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 SH3PXD2B NM_001017995.2(SH3PXD2B): c.969delG (p.Arg324Glyfs) deletion Pathogenic rs794728006 GRCh38 Chromosome 5, 172350406: 172350406
2 SH3PXD2B NM_001017995.2(SH3PXD2B): c.969delG (p.Arg324Glyfs) deletion Pathogenic rs794728006 GRCh37 Chromosome 5, 171777410: 171777410
3 INPPL1 NM_001567.3(INPPL1): c.1976C> T (p.Pro659Leu) single nucleotide variant Pathogenic rs397514508 GRCh37 Chromosome 11, 71944143: 71944143
4 INPPL1 NM_001567.3(INPPL1): c.1976C> T (p.Pro659Leu) single nucleotide variant Pathogenic rs397514508 GRCh38 Chromosome 11, 72233099: 72233099
5 INPPL1 NM_001567.3(INPPL1): c.545C> A (p.Ser182Ter) single nucleotide variant Pathogenic rs397514509 GRCh37 Chromosome 11, 71940160: 71940160
6 INPPL1 NM_001567.3(INPPL1): c.545C> A (p.Ser182Ter) single nucleotide variant Pathogenic rs397514509 GRCh38 Chromosome 11, 72229116: 72229116
7 INPPL1 NM_001567.3(INPPL1): c.768delA (p.Glu258Serfs) deletion Pathogenic rs797044468 GRCh37 Chromosome 11, 71940721: 71940721
8 INPPL1 NM_001567.3(INPPL1): c.768delA (p.Glu258Serfs) deletion Pathogenic rs797044468 GRCh38 Chromosome 11, 72229677: 72229677
9 INPPL1 NM_001567.3(INPPL1): c.2415+1G> A single nucleotide variant Pathogenic rs655423 GRCh37 Chromosome 11, 71945660: 71945660
10 INPPL1 NM_001567.3(INPPL1): c.2415+1G> A single nucleotide variant Pathogenic rs655423 GRCh38 Chromosome 11, 72234616: 72234616
11 INPPL1 NM_001567.3(INPPL1): c.1975C> T (p.Pro659Ser) single nucleotide variant Pathogenic rs397514510 GRCh37 Chromosome 11, 71944142: 71944142
12 INPPL1 NM_001567.3(INPPL1): c.1975C> T (p.Pro659Ser) single nucleotide variant Pathogenic rs397514510 GRCh38 Chromosome 11, 72233098: 72233098
13 INPPL1 NM_001567.3(INPPL1): c.278_282delAGACC (p.Gln93Profs) deletion Pathogenic rs797044469 GRCh37 Chromosome 11, 71939423: 71939427
14 INPPL1 NM_001567.3(INPPL1): c.278_282delAGACC (p.Gln93Profs) deletion Pathogenic rs797044469 GRCh38 Chromosome 11, 72228379: 72228383
15 INPPL1 NM_001567.3(INPPL1): c.1201C> T (p.Arg401Trp) single nucleotide variant Pathogenic rs397514511 GRCh37 Chromosome 11, 71941843: 71941843
16 INPPL1 NM_001567.3(INPPL1): c.1201C> T (p.Arg401Trp) single nucleotide variant Pathogenic rs397514511 GRCh38 Chromosome 11, 72230799: 72230799
17 INPPL1 NM_001567.3(INPPL1): c.2164T> A (p.Phe722Ile) single nucleotide variant Pathogenic rs397514512 GRCh37 Chromosome 11, 71944740: 71944740
18 INPPL1 NM_001567.3(INPPL1): c.2164T> A (p.Phe722Ile) single nucleotide variant Pathogenic rs397514512 GRCh38 Chromosome 11, 72233696: 72233696
19 INPPL1 NM_001567.3(INPPL1): c.94_121del28 (p.Glu32Metfs) deletion Pathogenic rs797044470 GRCh37 Chromosome 11, 71936122: 71936149
20 INPPL1 NM_001567.3(INPPL1): c.94_121del28 (p.Glu32Metfs) deletion Pathogenic rs797044470 GRCh38 Chromosome 11, 72225078: 72225105
21 INPPL1 NM_001567.3(INPPL1): c.24_39del16 (p.Gly9Trpfs) deletion no interpretation for the single variant rs878853119 GRCh37 Chromosome 11, 71936052: 71936067
22 INPPL1 NM_001567.3(INPPL1): c.24_39del16 (p.Gly9Trpfs) deletion no interpretation for the single variant rs878853119 GRCh38 Chromosome 11, 72225008: 72225023
23 INPPL1 NM_001567.3(INPPL1): c.35dupG (p.Ala13Argfs) duplication no interpretation for the single variant rs878853122 GRCh37 Chromosome 11, 71936063: 71936063
24 INPPL1 NM_001567.3(INPPL1): c.35dupG (p.Ala13Argfs) duplication no interpretation for the single variant rs878853122 GRCh38 Chromosome 11, 72225019: 72225019
25 INPPL1 NM_001567.3(INPPL1): c.753G> C (p.Gln251His) single nucleotide variant no interpretation for the single variant rs878853120 GRCh37 Chromosome 11, 71940602: 71940602
26 INPPL1 NM_001567.3(INPPL1): c.753G> C (p.Gln251His) single nucleotide variant no interpretation for the single variant rs878853120 GRCh38 Chromosome 11, 72229558: 72229558
27 INPPL1 NM_001567.3(INPPL1): c.768_769delAG (p.Glu258Alafs) deletion Pathogenic rs746647683 GRCh37 Chromosome 11, 71940721: 71940722
28 INPPL1 NM_001567.3(INPPL1): c.768_769delAG (p.Glu258Alafs) deletion Pathogenic rs746647683 GRCh38 Chromosome 11, 72229677: 72229678
29 INPPL1 NM_001567.3(INPPL1): c.1687_1691delACCTC (p.Thr563Glyfs) deletion no interpretation for the single variant rs878853121 GRCh37 Chromosome 11, 71943355: 71943359
30 INPPL1 NM_001567.3(INPPL1): c.1687_1691delACCTC (p.Thr563Glyfs) deletion no interpretation for the single variant rs878853121 GRCh38 Chromosome 11, 72232311: 72232315
31 INPPL1 NM_001567.3(INPPL1): c.2071C> T (p.Arg691Trp) single nucleotide variant Pathogenic rs878853123 GRCh37 Chromosome 11, 71944515: 71944515
32 INPPL1 NM_001567.3(INPPL1): c.2071C> T (p.Arg691Trp) single nucleotide variant Pathogenic rs878853123 GRCh38 Chromosome 11, 72233471: 72233471
33 INPPL1 NM_001567.3(INPPL1): c.1845dup (p.Ile616Tyrfs) duplication Pathogenic rs1135401750 GRCh38 Chromosome 11, 72232758: 72232758
34 INPPL1 NM_001567.3(INPPL1): c.1845dup (p.Ile616Tyrfs) duplication Pathogenic rs1135401750 GRCh37 Chromosome 11, 71943802: 71943802
35 INPPL1 NM_001567.3(INPPL1): c.1115delG (p.Arg372Leufs) deletion no interpretation for the single variant rs1135401751 GRCh37 Chromosome 11, 71941430: 71941430
36 INPPL1 NM_001567.3(INPPL1): c.1115delG (p.Arg372Leufs) deletion no interpretation for the single variant rs1135401751 GRCh38 Chromosome 11, 72230386: 72230386
37 INPPL1 NM_001567.3(INPPL1): c.2331C> G (p.Tyr777Ter) single nucleotide variant no interpretation for the single variant rs368970014 GRCh37 Chromosome 11, 71945575: 71945575
38 INPPL1 NM_001567.3(INPPL1): c.2331C> G (p.Tyr777Ter) single nucleotide variant no interpretation for the single variant rs368970014 GRCh38 Chromosome 11, 72234531: 72234531
39 INPPL1 NM_001567.3(INPPL1): c.1636G> A (p.Val546Ile) single nucleotide variant no interpretation for the single variant rs376117918 GRCh37 Chromosome 11, 71943304: 71943304
40 INPPL1 NM_001567.3(INPPL1): c.1636G> A (p.Val546Ile) single nucleotide variant no interpretation for the single variant rs376117918 GRCh38 Chromosome 11, 72232260: 72232260

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 skeletal system development GO:0001501 9.32 PHEX SH3PXD2B
2 bone development GO:0060348 9.26 PHEX SH3PXD2B
3 cellular response to vitamin D GO:0071305 9.16 FGF23 PHEX
4 cellular response to parathyroid hormone stimulus GO:0071374 8.96 FGF23 PHEX
5 response to sodium phosphate GO:1904383 8.62 FGF23 PHEX

Molecular functions related to Opsismodysplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 SH2 domain binding GO:0042169 8.62 INPPL1 SH3PXD2B

Sources for Opsismodysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....