MCID: SPN348
MIFTS: 28

Spondylometaphyseal Dysplasia, Axial

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

Aliases & Classifications for Spondylometaphyseal Dysplasia, Axial

MalaCards integrated aliases for Spondylometaphyseal Dysplasia, Axial:

Name: Spondylometaphyseal Dysplasia, Axial 57 75 73
Axial Spondylometaphyseal Dysplasia 53 59
Spondylometaphyseal Dysplasia Axial 29 6
Axial Smd 57 53
Smdax 57 75
Spondylometaphyseal Dysplasia Axial Type 53
Smd, Axial 57
Smd Axial 53

Characteristics:

Orphanet epidemiological data:

59
axial spondylometaphyseal dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable skeletal phenotype


HPO:

32
spondylometaphyseal dysplasia, axial:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spondylometaphyseal Dysplasia, Axial

UniProtKB/Swiss-Prot : 75 Spondylometaphyseal dysplasia, axial: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDAX is characterized by metaphyseal changes of truncal-juxtatruncal bones, including the proximal femora. Main clinical features are postnatal growth failure, rhizomelic short stature in early childhood evolving into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and function rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on fundoscopic examination and cone-rod dystrophy on electroretinogram. The radiological hallmarks include short ribs with flared, cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora.

MalaCards based summary : Spondylometaphyseal Dysplasia, Axial, also known as axial spondylometaphyseal dysplasia, is related to spondyloepimetaphyseal dysplasia, strudwick type. An important gene associated with Spondylometaphyseal Dysplasia, Axial is C21orf2 (Chromosome 21 Open Reading Frame 2). Affiliated tissues include bone and retina, and related phenotypes are hypertelorism and frontal bossing

NIH Rare Diseases : 53 Axial spondylometaphyseal dysplasia is a genetic disorder of bone growth. The term “axial” means towards the center of the body. “Sphondylos” is a Greek term meaning vertebra. “Metaphyseal dysplasia” refers to abnormalities at the ends of long bones. Axial spondylometaphyseal dysplasia primarily affects the bones of the chest, pelvis, spine, upper arms and upper legs, and results in shortened stature. For reasons not well understood, this rare skeletal dysplasia is also associated with early and progressive vision loss. The underlying genetic cause of axial spondylometaphyseal dysplasia is currently unknown. It is thought to be inherited in an autosomal recessive fashion.

OMIM : 57 Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on electroretinogram. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora (summary by Suzuki et al., 2011). (602271)

Related Diseases for Spondylometaphyseal Dysplasia, Axial

Diseases related to Spondylometaphyseal Dysplasia, Axial via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 spondyloepimetaphyseal dysplasia, strudwick type 10.0

Symptoms & Phenotypes for Spondylometaphyseal Dysplasia, Axial

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
optic atrophy
pigmentary retinal degeneration
reduced visual fields
narrowing of retinal vessels
more
Skeletal Limbs:
coxa vara
rhizomelic limb shortening
irregular proximal femoral metaphyses
short femoral necks

GenitourinaryInternal GenitaliaMale:
reduced sperm motility

AbdomenSpleen:
splenomegaly (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
widened anterior ribs
anterior cupping of ribs

Skeletal Pelvis:
lacy iliac wings
narrow sacrosciatic notch

Growth Height:
short stature

Skeletal:
spondylometaphyseal dysplasia

Skeletal Spine:
mild platyspondyly

Chest External Features:
small chest
thoracic deformation
harrison grooves (in some patients)

Respiratory Lung:
respiratory distress in neonatal period (in some patients)
pneumonia, recurrent (in some patients)

Skeletal Hands:
metacarpal shortening (in some patients)


Clinical features from OMIM:

602271

Human phenotypes related to Spondylometaphyseal Dysplasia, Axial:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
2 frontal bossing 59 32 frequent (33%) Frequent (79-30%) HP:0002007
3 delayed skeletal maturation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002750
4 short nose 59 32 occasional (7.5%) Occasional (29-5%) HP:0003196
5 anteverted nares 59 32 occasional (7.5%) Occasional (29-5%) HP:0000463
6 visual impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000505
7 optic atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0000648
8 short stature 59 32 Very frequent (99-80%) HP:0004322
9 photophobia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000613
10 platyspondyly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000926
11 telecanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000506
12 rhizomelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008905
13 downslanted palpebral fissures 59 32 occasional (7.5%) Occasional (29-5%) HP:0000494
14 proptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000520
15 astigmatism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000483
16 rod-cone dystrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000510
17 cupped ribs 59 32 hallmark (90%) Very frequent (99-80%) HP:0000887
18 proximal femoral metaphyseal irregularity 59 32 frequent (33%) Frequent (79-30%) HP:0003411
19 irregular iliac crest 59 32 frequent (33%) Frequent (79-30%) HP:0003796
20 thoracic hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0005257
21 nystagmus 32 HP:0000639
22 abnormality of the metaphysis 59 Very frequent (99-80%)
23 recurrent pneumonia 32 HP:0006532
24 coxa vara 32 HP:0002812
25 spondylometaphyseal dysplasia 32 HP:0002657
26 anterior rib cupping 32 HP:0000907
27 short femoral neck 32 HP:0100864
28 narrow greater sacrosciatic notches 32 HP:0003375

Drugs & Therapeutics for Spondylometaphyseal Dysplasia, Axial

Search Clinical Trials , NIH Clinical Center for Spondylometaphyseal Dysplasia, Axial

Genetic Tests for Spondylometaphyseal Dysplasia, Axial

Genetic tests related to Spondylometaphyseal Dysplasia, Axial:

# Genetic test Affiliating Genes
1 Spondylometaphyseal Dysplasia Axial 29 C21orf2

Anatomical Context for Spondylometaphyseal Dysplasia, Axial

MalaCards organs/tissues related to Spondylometaphyseal Dysplasia, Axial:

41
Bone, Retina

Publications for Spondylometaphyseal Dysplasia, Axial

Articles related to Spondylometaphyseal Dysplasia, Axial:

# Title Authors Year
1
Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations. ( 28123176 )
2017
2
Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations. ( 26974433 )
2016
3
Axial spondylometaphyseal dysplasia with retinitis pigmentosa--a clinical report and diagnostic clues. ( 23371363 )
2013
4
Axial spondylometaphyseal dysplasia: additional reports. ( 21910225 )
2011
5
Axial spondylometaphyseal dysplasia: Confirmation and further delineation of a new SMD with retinal dystrophy. ( 20503334 )
2010
6
Axial spondylometaphyseal dysplasia. ( 9266195 )
1997

Variations for Spondylometaphyseal Dysplasia, Axial

UniProtKB/Swiss-Prot genetic disease variations for Spondylometaphyseal Dysplasia, Axial:

75
# Symbol AA change Variation ID SNP ID
1 C21orf2 p.Arg73Pro VAR_075924 rs140451304
2 C21orf2 p.Tyr107His VAR_075925 rs763623409
3 C21orf2 p.Pro116Leu VAR_075926 rs922930539
4 C21orf2 p.Leu224Pro VAR_075927
5 C21orf2 p.Val111Met VAR_079182 rs555164150

ClinVar genetic disease variations for Spondylometaphyseal Dysplasia, Axial:

6
(show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 C21orf2 NM_001271441.1(C21orf2): c.218G> C (p.Arg73Pro) single nucleotide variant Pathogenic/Likely pathogenic rs140451304 GRCh38 Chromosome 21, 44333188: 44333188
2 C21orf2 NM_001271441.1(C21orf2): c.218G> C (p.Arg73Pro) single nucleotide variant Pathogenic/Likely pathogenic rs140451304 GRCh37 Chromosome 21, 45753071: 45753071
3 C21orf2 NM_004928.2(C21orf2): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs1114167892 GRCh37 Chromosome 21, 45750181: 45750181
4 C21orf2 NM_004928.2(C21orf2): c.671T> C (p.Leu224Pro) single nucleotide variant Pathogenic rs1114167892 GRCh38 Chromosome 21, 44330298: 44330298
5 C21orf2 NM_004928.2(C21orf2): c.103delA (p.Ile35Phefs) deletion Pathogenic rs1114167893 GRCh37 Chromosome 21, 45755681: 45755681
6 C21orf2 NM_004928.2(C21orf2): c.103delA (p.Ile35Phefs) deletion Pathogenic rs1114167893 GRCh38 Chromosome 21, 44335798: 44335798
7 C21orf2 NM_004928.2(C21orf2): c.545+1G> A single nucleotide variant Pathogenic rs778222701 GRCh38 Chromosome 21, 44331842: 44331842
8 C21orf2 NM_004928.2(C21orf2): c.545+1G> A single nucleotide variant Pathogenic rs778222701 GRCh37 Chromosome 21, 45751725: 45751725
9 C21orf2 NM_004928.2(C21orf2): c.643-23A> T single nucleotide variant Pathogenic rs1131690800 GRCh37 Chromosome 21, 45750232: 45750232
10 C21orf2 NM_004928.2(C21orf2): c.643-23A> T single nucleotide variant Pathogenic rs1131690800 GRCh38 Chromosome 21, 44330349: 44330349
11 C21orf2 NM_004928.2(C21orf2): c.319T> C (p.Tyr107His) single nucleotide variant Pathogenic rs763623409 GRCh38 Chromosome 21, 44333087: 44333087
12 C21orf2 NM_004928.2(C21orf2): c.319T> C (p.Tyr107His) single nucleotide variant Pathogenic rs763623409 GRCh37 Chromosome 21, 45752970: 45752970
13 C21orf2 NM_004928.2(C21orf2): c.347C> T (p.Pro116Leu) single nucleotide variant Pathogenic rs922930539 GRCh38 Chromosome 21, 44333059: 44333059
14 C21orf2 NM_004928.2(C21orf2): c.347C> T (p.Pro116Leu) single nucleotide variant Pathogenic rs922930539 GRCh37 Chromosome 21, 45752942: 45752942
15 C21orf2 NM_004928.2(C21orf2): c.331G> A (p.Val111Met) single nucleotide variant Pathogenic rs555164150 GRCh38 Chromosome 21, 44333075: 44333075
16 C21orf2 NM_004928.2(C21orf2): c.331G> A (p.Val111Met) single nucleotide variant Pathogenic rs555164150 GRCh37 Chromosome 21, 45752958: 45752958

Expression for Spondylometaphyseal Dysplasia, Axial

Search GEO for disease gene expression data for Spondylometaphyseal Dysplasia, Axial.

Pathways for Spondylometaphyseal Dysplasia, Axial

GO Terms for Spondylometaphyseal Dysplasia, Axial

Sources for Spondylometaphyseal Dysplasia, Axial

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