SMDAX
MCID: SPN348
MIFTS: 32

Spondylometaphyseal Dysplasia, Axial (SMDAX)

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

Aliases & Classifications for Spondylometaphyseal Dysplasia, Axial

MalaCards integrated aliases for Spondylometaphyseal Dysplasia, Axial:

Name: Spondylometaphyseal Dysplasia, Axial 57 72 70
Axial Spondylometaphyseal Dysplasia 20 58 29 6
Axial Smd 57 20
Smdax 57 72
Spondylometaphyseal Dysplasia Axial Type 20
Dysplasia, Spondylometaphyseal, Axial 39
Smd, Axial 57
Smd Axial 20

Characteristics:

Orphanet epidemiological data:

58
axial spondylometaphyseal dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable skeletal phenotype


HPO:

31
spondylometaphyseal dysplasia, axial:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 602271
OMIM Phenotypic Series 57 PS184255
MeSH 44 D010009
MESH via Orphanet 45 C535795
ICD10 via Orphanet 33 Q77.8
UMLS via Orphanet 71 C1865695
Orphanet 58 ORPHA168549
MedGen 41 C1865695
UMLS 70 C1865695

Summaries for Spondylometaphyseal Dysplasia, Axial

UniProtKB/Swiss-Prot : 72 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 and retinitis pigmentosa. An important gene associated with Spondylometaphyseal Dysplasia, Axial is CFAP410 (Cilia And Flagella Associated Protein 410). Affiliated tissues include eye and retina, and related phenotypes are delayed skeletal maturation and visual impairment

GARD : 20 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) (Updated 05-Apr-2021)

Related Diseases for Spondylometaphyseal Dysplasia, Axial

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

(show all 14)
# Related Disease Score Top Affiliating Genes
1 spondyloepimetaphyseal dysplasia, strudwick type 10.5
2 retinitis pigmentosa 10.4
3 neuroretinitis 10.4
4 retinitis 10.4
5 fundus dystrophy 10.3
6 inherited retinal disorder 10.3
7 retinal degeneration 10.2
8 cone-rod dystrophy 2 10.1
9 short-rib thoracic dysplasia 1 with or without polydactyly 10.1
10 3-methylglutaconic aciduria, type iii 10.1
11 short-rib thoracic dysplasia 6 with or without polydactyly 10.1
12 autosomal recessive disease 10.1
13 metaphyseal dysplasia 10.1
14 ciliopathy 10.1

Graphical network of the top 20 diseases related to Spondylometaphyseal Dysplasia, Axial:



Diseases related to Spondylometaphyseal Dysplasia, Axial

Symptoms & Phenotypes for Spondylometaphyseal Dysplasia, Axial

Human phenotypes related to Spondylometaphyseal Dysplasia, Axial:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
2 visual impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000505
3 platyspondyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000926
4 rod-cone dystrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000510
5 rhizomelia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008905
6 cupped ribs 58 31 hallmark (90%) Very frequent (99-80%) HP:0000887
7 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
8 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
9 thoracic hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0005257
10 proximal femoral metaphyseal irregularity 58 31 frequent (33%) Frequent (79-30%) HP:0003411
11 irregular iliac crest 58 31 frequent (33%) Frequent (79-30%) HP:0003796
12 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
13 short nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0003196
14 anteverted nares 58 31 occasional (7.5%) Occasional (29-5%) HP:0000463
15 photophobia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000613
16 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
17 proptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000520
18 telecanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000506
19 astigmatism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000483
20 splenomegaly 31 very rare (1%) HP:0001744
21 short stature 58 31 Very frequent (99-80%) HP:0004322
22 nystagmus 31 HP:0000639
23 abnormality of the metaphysis 58 Very frequent (99-80%)
24 recurrent pneumonia 31 HP:0006532
25 coxa vara 31 HP:0002812
26 retinal degeneration 31 HP:0000546
27 anterior rib cupping 31 HP:0000907
28 short femoral neck 31 HP:0100864
29 spondylometaphyseal dysplasia 31 HP:0002657
30 reduced sperm motility 31 HP:0012207
31 narrow greater sciatic notch 31 HP:0003375

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
nystagmus
optic atrophy
pigmentary retinal degeneration
reduced visual fields
low to no night vision
more
Skeletal Limbs:
coxa vara
rhizomelic limb shortening
irregular proximal femoral metaphyses
short femoral necks

Genitourinary Internal Genitalia Male:
reduced sperm motility

Abdomen Spleen:
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 (Updated 05-Apr-2021)

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 Axial Spondylometaphyseal Dysplasia 29 CFAP410

Anatomical Context for Spondylometaphyseal Dysplasia, Axial

MalaCards organs/tissues related to Spondylometaphyseal Dysplasia, Axial:

40
Eye, Retina

Publications for Spondylometaphyseal Dysplasia, Axial

Articles related to Spondylometaphyseal Dysplasia, Axial:

(show all 12)
# Title Authors PMID Year
1
Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic involvement: Extending the phenotypic spectrum. 6 57 61
28422394 2017
2
Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations. 6 61 57
26974433 2016
3
Axial spondylometaphyseal dysplasia: additional reports. 6 57 61
21910225 2011
4
Axial spondylometaphyseal dysplasia: Confirmation and further delineation of a new SMD with retinal dystrophy. 57 6 61
20503334 2010
5
Identification of Novel Mutations in the LRR-Cap Domain of C21orf2 in Japanese Patients With Retinitis Pigmentosa and Cone-Rod Dystrophy. 57 6
27548899 2016
6
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. 57 6
26167768 2015
7
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. 57 6
23105016 2013
8
Retinitis pigmentosa with osteochondrodysplasia in siblings. 6 57
11702989 2001
9
Axial spondylometaphyseal dysplasia. 57 61
9266195 1997
10
A newly recognized skeletal dysplasia with rhizomelic limbs and retinitis pigmentosa. 57
15372527 2004
11
Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations. 61
28123176 2017
12
Axial spondylometaphyseal dysplasia with retinitis pigmentosa--a clinical report and diagnostic clues. 61
23371363 2013

Variations for Spondylometaphyseal Dysplasia, Axial

ClinVar genetic disease variations for Spondylometaphyseal Dysplasia, Axial:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CFAP410 NM_004928.3(CFAP410):c.671T>C (p.Leu224Pro) SNV Pathogenic 428574 rs1114167892 GRCh37: 21:45750181-45750181
GRCh38: 21:44330298-44330298
2 CFAP410 NM_004928.3(CFAP410):c.319T>C (p.Tyr107His) SNV Pathogenic 428580 rs763623409 GRCh37: 21:45752970-45752970
GRCh38: 21:44333087-44333087
3 CFAP410 NM_004928.3(CFAP410):c.545+1G>A SNV Pathogenic 428578 rs778222701 GRCh37: 21:45751725-45751725
GRCh38: 21:44331842-44331842
4 CFAP410 NM_004928.3(CFAP410):c.103del (p.Ile35fs) Deletion Pathogenic 428575 rs1114167893 GRCh37: 21:45755681-45755681
GRCh38: 21:44335798-44335798
5 CFAP410 NM_004928.3(CFAP410):c.331G>A (p.Val111Met) SNV Pathogenic 428582 rs555164150 GRCh37: 21:45752958-45752958
GRCh38: 21:44333075-44333075
6 CFAP410 NM_004928.3(CFAP410):c.643-23A>T SNV Pathogenic 428579 rs1131690800 GRCh37: 21:45750232-45750232
GRCh38: 21:44330349-44330349
7 CFAP410 NM_004928.3(CFAP410):c.218G>C (p.Arg73Pro) SNV Pathogenic 428573 rs140451304 GRCh37: 21:45753071-45753071
GRCh38: 21:44333188-44333188
8 CFAP410 NM_004928.3(CFAP410):c.347C>T (p.Pro116Leu) SNV Pathogenic 428581 rs922930539 GRCh37: 21:45752942-45752942
GRCh38: 21:44333059-44333059

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

72
# Symbol AA change Variation ID SNP ID
1 CFAP410 p.Arg73Pro VAR_075924 rs140451304
2 CFAP410 p.Tyr107His VAR_075925 rs763623409
3 CFAP410 p.Pro116Leu VAR_075926 rs922930539
4 CFAP410 p.Leu224Pro VAR_075927 rs111416789
5 CFAP410 p.Val111Met VAR_079182 rs555164150

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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