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 58 77 54 60 76 38 30 13 6 41 74
Opsmd 58 76

Characteristics:

Orphanet epidemiological data:

60
opsismodysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
opsismodysplasia:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Opsismodysplasia

OMIM : 58 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)

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 : 54 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 : 76 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 : 77 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:

60 33 (show all 49)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000256
2 frontal bossing 60 33 hallmark (90%) Very frequent (99-80%) HP:0002007
3 abnormality of epiphysis morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0005930
4 respiratory insufficiency 60 33 hallmark (90%) Very frequent (99-80%) HP:0002093
5 delayed skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0002750
6 depressed nasal bridge 60 33 hallmark (90%) Very frequent (99-80%) HP:0005280
7 short nose 60 33 hallmark (90%) Very frequent (99-80%) HP:0003196
8 abnormality of the metaphysis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000944
9 brachydactyly 60 33 hallmark (90%) Very frequent (99-80%) HP:0001156
10 severe short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0003510
11 large fontanelles 60 33 hallmark (90%) Very frequent (99-80%) HP:0000239
12 tapered finger 60 33 hallmark (90%) Very frequent (99-80%) HP:0001182
13 hypoplastic pubic bone 60 33 hallmark (90%) Very frequent (99-80%) HP:0003173
14 hypoplastic ischia 60 33 hallmark (90%) Very frequent (99-80%) HP:0003175
15 squared iliac bones 60 33 hallmark (90%) Very frequent (99-80%) HP:0003177
16 hypoplastic vertebral bodies 60 33 hallmark (90%) Very frequent (99-80%) HP:0008479
17 abnormally ossified vertebrae 33 hallmark (90%) HP:0100569
18 muscular hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001252
19 recurrent respiratory infections 60 33 frequent (33%) Frequent (79-30%) HP:0002205
20 flat occiput 60 33 frequent (33%) Frequent (79-30%) HP:0005469
21 pectus excavatum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000767
22 splenomegaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0001744
23 hepatomegaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0002240
24 joint stiffness 60 33 occasional (7.5%) Occasional (29-5%) HP:0001387
25 broad thumb 60 33 occasional (7.5%) Occasional (29-5%) HP:0011304
26 narrow chest 60 33 occasional (7.5%) Occasional (29-5%) HP:0000774
27 blue sclerae 60 33 occasional (7.5%) Occasional (29-5%) HP:0000592
28 hypophosphatemia 33 occasional (7.5%) HP:0002148
29 renal phosphate wasting 33 occasional (7.5%) HP:0000117
30 hypertelorism 33 HP:0000316
31 short neck 33 HP:0000470
32 anteverted nares 33 HP:0000463
33 long philtrum 33 HP:0000343
34 edema 33 HP:0000969
35 short palm 33 HP:0004279
36 short long bone 33 HP:0003026
37 short foot 33 HP:0001773
38 rhizomelia 33 HP:0008905
39 polyhydramnios 33 HP:0001561
40 disproportionate short-limb short stature 33 HP:0008873
41 flat acetabular roof 33 HP:0003180
42 abnormal vertebral ossification 60 Very frequent (99-80%)
43 generalized hypotonia 33 HP:0001290
44 bell-shaped thorax 33 HP:0001591
45 anterior rib cupping 33 HP:0000907
46 protuberant abdomen 33 HP:0001538
47 metaphyseal cupping 33 HP:0003021
48 severe platyspondyly 33 HP:0004565
49 posterior rib cupping 33 HP:0000922

Symptoms via clinical synopsis from OMIM:

58
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

MGI Mouse Phenotypes related to Opsismodysplasia:

47
# 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 FGF23 INPPL1 PHEX SH3PXD2B
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 30 INPPL1

Anatomical Context for Opsismodysplasia

MalaCards organs/tissues related to Opsismodysplasia:

42
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
Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. ( 23273567 )
2013
7
Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. ( 23273569 )
2013
8
Opsismodysplasia: implications of mutations in the developmental gene INPPL1. ( 23464704 )
2013
9
Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. ( 23552673 )
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:

76
# 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 36)
# Gene Variation Type Significance SNP ID Assembly Location
1 INPPL1 NM_001567.3(INPPL1): c.1976C> T (p.Pro659Leu) single nucleotide variant Pathogenic rs397514508 GRCh37 Chromosome 11, 71944143: 71944143
2 INPPL1 NM_001567.3(INPPL1): c.1976C> T (p.Pro659Leu) single nucleotide variant Pathogenic rs397514508 GRCh38 Chromosome 11, 72233099: 72233099
3 INPPL1 NM_001567.3(INPPL1): c.545C> A (p.Ser182Ter) single nucleotide variant Pathogenic rs397514509 GRCh37 Chromosome 11, 71940160: 71940160
4 INPPL1 NM_001567.3(INPPL1): c.545C> A (p.Ser182Ter) single nucleotide variant Pathogenic rs397514509 GRCh38 Chromosome 11, 72229116: 72229116
5 INPPL1 NM_001567.3(INPPL1): c.768delA (p.Glu258Serfs) deletion Pathogenic rs797044468 GRCh37 Chromosome 11, 71940721: 71940721
6 INPPL1 NM_001567.3(INPPL1): c.768delA (p.Glu258Serfs) deletion Pathogenic rs797044468 GRCh38 Chromosome 11, 72229677: 72229677
7 INPPL1 NM_001567.3(INPPL1): c.2415+1G> A single nucleotide variant Pathogenic rs655423 GRCh37 Chromosome 11, 71945660: 71945660
8 INPPL1 NM_001567.3(INPPL1): c.2415+1G> A single nucleotide variant Pathogenic rs655423 GRCh38 Chromosome 11, 72234616: 72234616
9 INPPL1 NM_001567.3(INPPL1): c.1975C> T (p.Pro659Ser) single nucleotide variant Pathogenic rs397514510 GRCh37 Chromosome 11, 71944142: 71944142
10 INPPL1 NM_001567.3(INPPL1): c.1975C> T (p.Pro659Ser) single nucleotide variant Pathogenic rs397514510 GRCh38 Chromosome 11, 72233098: 72233098
11 INPPL1 NM_001567.3(INPPL1): c.278_282delAGACC (p.Gln93Profs) deletion Pathogenic rs797044469 GRCh37 Chromosome 11, 71939423: 71939427
12 INPPL1 NM_001567.3(INPPL1): c.278_282delAGACC (p.Gln93Profs) deletion Pathogenic rs797044469 GRCh38 Chromosome 11, 72228379: 72228383
13 INPPL1 NM_001567.3(INPPL1): c.1201C> T (p.Arg401Trp) single nucleotide variant Pathogenic rs397514511 GRCh37 Chromosome 11, 71941843: 71941843
14 INPPL1 NM_001567.3(INPPL1): c.1201C> T (p.Arg401Trp) single nucleotide variant Pathogenic rs397514511 GRCh38 Chromosome 11, 72230799: 72230799
15 INPPL1 NM_001567.3(INPPL1): c.2164T> A (p.Phe722Ile) single nucleotide variant Pathogenic rs397514512 GRCh37 Chromosome 11, 71944740: 71944740
16 INPPL1 NM_001567.3(INPPL1): c.2164T> A (p.Phe722Ile) single nucleotide variant Pathogenic rs397514512 GRCh38 Chromosome 11, 72233696: 72233696
17 INPPL1 NM_001567.3(INPPL1): c.94_121del (p.Glu32Metfs) deletion Pathogenic rs797044470 GRCh37 Chromosome 11, 71936122: 71936149
18 INPPL1 NM_001567.3(INPPL1): c.94_121del (p.Glu32Metfs) deletion Pathogenic rs797044470 GRCh38 Chromosome 11, 72225078: 72225105
19 INPPL1 NM_001567.3(INPPL1): c.24_39delGGGCCCGGGGGGCGCC (p.Gly9Trpfs) deletion no interpretation for the single variant rs878853119 GRCh37 Chromosome 11, 71936052: 71936067
20 INPPL1 NM_001567.3(INPPL1): c.24_39delGGGCCCGGGGGGCGCC (p.Gly9Trpfs) deletion no interpretation for the single variant rs878853119 GRCh38 Chromosome 11, 72225008: 72225023
21 INPPL1 NM_001567.3(INPPL1): c.35dup (p.Ala13Argfs) duplication no interpretation for the single variant rs878853122 GRCh37 Chromosome 11, 71936063: 71936063
22 INPPL1 NM_001567.3(INPPL1): c.35dup (p.Ala13Argfs) duplication no interpretation for the single variant rs878853122 GRCh38 Chromosome 11, 72225019: 72225019
23 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
24 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
25 INPPL1 NM_001567.3(INPPL1): c.768_769delAG (p.Glu258Alafs) deletion Pathogenic rs746647683 GRCh37 Chromosome 11, 71940721: 71940722
26 INPPL1 NM_001567.3(INPPL1): c.768_769delAG (p.Glu258Alafs) deletion Pathogenic rs746647683 GRCh38 Chromosome 11, 72229677: 72229678
27 INPPL1 NM_001567.3(INPPL1): c.1687_1691delACCTC (p.Thr563Glyfs) deletion no interpretation for the single variant rs878853121 GRCh37 Chromosome 11, 71943355: 71943359
28 INPPL1 NM_001567.3(INPPL1): c.1687_1691delACCTC (p.Thr563Glyfs) deletion no interpretation for the single variant rs878853121 GRCh38 Chromosome 11, 72232311: 72232315
29 INPPL1 NM_001567.3(INPPL1): c.2071C> T (p.Arg691Trp) single nucleotide variant Pathogenic rs878853123 GRCh37 Chromosome 11, 71944515: 71944515
30 INPPL1 NM_001567.3(INPPL1): c.2071C> T (p.Arg691Trp) single nucleotide variant Pathogenic rs878853123 GRCh38 Chromosome 11, 72233471: 72233471
31 INPPL1 NM_001567.3(INPPL1): c.1845dup (p.Ile616Tyrfs) duplication Pathogenic rs1135401750 GRCh38 Chromosome 11, 72232758: 72232758
32 INPPL1 NM_001567.3(INPPL1): c.1845dup (p.Ile616Tyrfs) duplication Pathogenic rs1135401750 GRCh37 Chromosome 11, 71943802: 71943802
33 INPPL1 NM_001567.3(INPPL1): c.1636G> A (p.Val546Ile) single nucleotide variant Uncertain significance rs376117918 GRCh37 Chromosome 11, 71943304: 71943304
34 INPPL1 NM_001567.3(INPPL1): c.1636G> A (p.Val546Ile) single nucleotide variant Uncertain significance rs376117918 GRCh38 Chromosome 11, 72232260: 72232260
35 INPPL1 NM_001567.4(INPPL1): c.1108_1155del (p.Ser370_Lys385del) deletion Uncertain significance GRCh38 Chromosome 11, 72230379: 72230426
36 INPPL1 NM_001567.4(INPPL1): c.1108_1155del (p.Ser370_Lys385del) deletion Uncertain significance GRCh37 Chromosome 11, 71941423: 71941470

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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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