MCID: SPN310
MIFTS: 41

Spondylocostal Dysostosis 1, Autosomal Recessive

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

Aliases & Classifications for Spondylocostal Dysostosis 1, Autosomal Recessive

MalaCards integrated aliases for Spondylocostal Dysostosis 1, Autosomal Recessive:

Name: Spondylocostal Dysostosis 1, Autosomal Recessive 57 75 29 6
Jarcho-Levin Syndrome 57 75 29 6 73
Spondylothoracic Dysostosis 57 75
Spondylothoracic Dysplasia 57 75
Costovertebral Dysplasia 57 75
Vertebral Anomalies 57 55
Scdo1 57 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
spondylocostal dysostosis 1, autosomal recessive:
Inheritance autosomal recessive inheritance
Mortality/Aging death in infancy


Classifications:



External Ids:

OMIM 57 277300
MedGen 42 C0265343
MeSH 44 D004413
UMLS 73 C0265343

Summaries for Spondylocostal Dysostosis 1, Autosomal Recessive

UniProtKB/Swiss-Prot : 75 Spondylocostal dysostosis 1, autosomal recessive: A condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life.

MalaCards based summary : Spondylocostal Dysostosis 1, Autosomal Recessive, also known as jarcho-levin syndrome, is related to spondylocostal dysostosis 3, autosomal recessive and hajdu-cheney syndrome. An important gene associated with Spondylocostal Dysostosis 1, Autosomal Recessive is DLL3 (Delta Like Canonical Notch Ligand 3), and among its related pathways/superpathways are Wnt / Hedgehog / Notch and Gene regulatory network modelling somitogenesis. Related phenotypes are short neck and rib fusion

OMIM : 57 The spondylocostal dysostoses are a heterogeneous group of axial skeletal disorders characterized by multiple segmentation defects of the vertebrae (SDV), malalignment of the ribs with variable points of intercostal fusion, and often a reduction in rib number. The term 'spondylocostal dysostosis' is best applied to those phenotypes with generalized SDV and a broadly symmetric thoracic cage (summary by Gucev et al., 2010). (277300)

Related Diseases for Spondylocostal Dysostosis 1, Autosomal Recessive

Diseases in the Spondylocostal Dysostosis, Autosomal Recessive family:

Spondylocostal Dysostosis 5 Spondylocostal Dysostosis 1, Autosomal Recessive
Spondylocostal Dysostosis 2, Autosomal Recessive Spondylocostal Dysostosis 3, Autosomal Recessive
Spondylocostal Dysostosis 4, Autosomal Recessive Spondylocostal Dysostosis 6, Autosomal Recessive
Spondylocostal Dysostosis 1 Spondylocostal Dysostosis 2
Spondylocostal Dysostosis 3 Spondylocostal Dysostosis 4

Diseases related to Spondylocostal Dysostosis 1, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 70)
# Related Disease Score Top Affiliating Genes
1 spondylocostal dysostosis 3, autosomal recessive 30.2 DLL3 HES7 LFNG MESP2
2 hajdu-cheney syndrome 29.7 DLL3 HES7
3 alagille syndrome 1 28.9 DLL3 MESP2
4 spondylocostal dysostosis, autosomal recessive 28.9 DLL3 HES7 LFNG MESP2
5 dysostosis 28.0 DLL3 HES7 LFNG MESP2
6 hydrocephalus, sprengel anomaly, and costovertebral dysplasia 12.3
7 sacral agenesis with vertebral anomalies 12.3
8 spondylocostal dysostosis 5 12.2
9 cleft palate short stature vertebral anomalies 12.2
10 polydactyly, postaxial, with dental and vertebral anomalies 12.0
11 spondylocostal dysostosis 1 11.2
12 vater/vacterl association 11.1
13 spondylocostal dysostosis 2, autosomal recessive 11.0
14 tethered cord syndrome 10.9
15 feingold syndrome 1 10.9
16 robinow syndrome, autosomal dominant 1 10.9
17 vacterl association with hydrocephalus 10.9
18 vacterl association, x-linked, with or without hydrocephalus 10.9
19 lateral meningocele syndrome 10.8
20 acrofacial dysostosis 1, nager type 10.8
21 oculocerebrocutaneous syndrome 10.8
22 pseudoachondroplasia 10.8
23 steinfeld syndrome 10.8
24 microphthalmia with limb anomalies 10.8
25 ritscher-schinzel syndrome 1 10.8
26 feingold syndrome 2 10.8
27 anophthalmos with limb anomalies 10.8
28 ichthyosis follicularis atrichia photophobia syndrome 10.8
29 thoraco abdominal enteric duplication 10.8
30 xk aprosencephaly 10.8
31 anus, imperforate 10.1
32 polydactyly 10.0
33 diastematomyelia 9.9
34 cleft palate, isolated 9.8
35 meningocele 9.8
36 vacterl association 9.8
37 cervicitis 9.8
38 dwarfism 9.8
39 neural tube defects 9.8
40 renal hypodysplasia/aplasia 1 9.8
41 tracheoesophageal fistula 9.8
42 neurenteric cyst 9.8
43 microtia 9.8
44 pfeiffer syndrome 9.6
45 fibromuscular dysplasia 9.6
46 hemifacial microsomia with radial defects 9.6
47 hemifacial microsomia 9.6
48 sprengel deformity 9.6
49 tetralogy of fallot 9.6
50 tracheoesophageal fistula with or without esophageal atresia 9.6

Graphical network of the top 20 diseases related to Spondylocostal Dysostosis 1, Autosomal Recessive:



Diseases related to Spondylocostal Dysostosis 1, Autosomal Recessive

Symptoms & Phenotypes for Spondylocostal Dysostosis 1, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Growth:
dwarfism

Chest:
rib anomalies
fused ribs

Neck:
short neck

Limbs:
normal length limbs

Spine:
hemivertebrae
vertebral fusion
block vertebrae
abnormal odontoid process

Resp:
respiratory infection

Thorax:
short trunk

Misc:
infantile death


Clinical features from OMIM:

277300

Human phenotypes related to Spondylocostal Dysostosis 1, Autosomal Recessive:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 short neck 32 HP:0000470
2 rib fusion 32 HP:0000902
3 recurrent respiratory infections 32 HP:0002205
4 hemivertebrae 32 HP:0002937
5 block vertebrae 32 HP:0003305
6 abnormality of the odontoid process 32 HP:0003310
7 severe short stature 32 HP:0003510
8 disproportionate short-trunk short stature 32 HP:0003521

MGI Mouse Phenotypes related to Spondylocostal Dysostosis 1, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.72 DLL3 HES7 LFNG MESP2 PAX1
2 growth/size/body region MP:0005378 9.65 DLL3 HES7 LFNG MESP2 PAX1
3 limbs/digits/tail MP:0005371 9.55 DLL3 HES7 LFNG MESP2 PAX1
4 mortality/aging MP:0010768 9.35 MESP2 PAX1 DLL3 HES7 LFNG
5 skeleton MP:0005390 9.02 DLL3 HES7 LFNG MESP2 PAX1

Drugs & Therapeutics for Spondylocostal Dysostosis 1, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spondylocostal Dysostosis 1, Autosomal Recessive

Genetic Tests for Spondylocostal Dysostosis 1, Autosomal Recessive

Genetic tests related to Spondylocostal Dysostosis 1, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spondylocostal Dysostosis 1, Autosomal Recessive 29 DLL3 MESP2
2 Jarcho-Levin Syndrome 29 HES7 LFNG MESP2

Anatomical Context for Spondylocostal Dysostosis 1, Autosomal Recessive

Publications for Spondylocostal Dysostosis 1, Autosomal Recessive

Articles related to Spondylocostal Dysostosis 1, Autosomal Recessive:

(show all 16)
# Title Authors Year
1
Ten year follow-up of Jarcho-Levin syndrome with thoracic insufficiency treated by VEPTR and MCGR VEPTR hybrid. ( 28608177 )
2017
2
Spondylocostal Dysostosis (Jarcho Levin Syndrome). ( 29270795 )
2017
3
Spondylocostal dysostosis (Jarcho-Levine syndrome) associated with occult spinal dysraphism: Report of two cases. ( 26167215 )
2015
4
Neurosurgical management of a large meningocele in Jarcho-Levin syndrome: clinical and radiological pearls. ( 26199296 )
2015
5
Neural Tube Defects in Jarcho-Levin Syndrome: Study of Twenty-Eight Cases. ( 25792257 )
2015
6
Jarcho-Levin syndrome with diastematomyelia: A case report and review of literature. ( 22408667 )
2011
7
Clinical and radiological distinction between spondylothoracic dysostosis (Lavy-Moseley syndrome) and spondylocostal dysostosis (Jarcho-Levin syndrome). ( 21174082 )
2011
8
[Jarcho-Levin syndrome associated with maternal hypothyroidism]. ( 22185858 )
2011
9
A case of Jarcho-Levin syndrome associated with bilateral cystic renal disease and wilms tumor: MR imaging findings. ( 19863205 )
2009
10
Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho- Levin syndrome. ( 18485326 )
2008
11
Jarcho-Levin syndrome presenting with diaphragmatic hernia. ( 18629769 )
2008
12
Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review. ( 12833407 )
2003
13
Detection of Jarcho-Levin syndrome at 12 weeks' gestation by nuchal translucency screening and three-dimensional ultrasound. ( 11360281 )
2001
14
Jarcho-Levin syndrome: report on a long-term follow-up of an untreated patient. ( 10218183 )
1999
15
Spondylothoracic dysplasia (Jarcho-Levin syndrome) in a Chinese baby. ( 1466945 )
1992
16
Prenatal findings in a case of spondylocostal dysplasia type I (Jarcho-Levin syndrome). ( 3287253 )
1988

Variations for Spondylocostal Dysostosis 1, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Spondylocostal Dysostosis 1, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 DLL3 p.Gly385Asp VAR_009952 rs104894674

ClinVar genetic disease variations for Spondylocostal Dysostosis 1, Autosomal Recessive:

6
(show top 50) (show all 106)
# Gene Variation Type Significance SNP ID Assembly Location
1 DLL3 NM_016941.3(DLL3): c.599_603dupGCGGT (p.Pro202Alafs) duplication Pathogenic rs786200899 GRCh38 Chromosome 19, 39503004: 39503008
2 DLL3 NM_016941.3(DLL3): c.599_603dupGCGGT (p.Pro202Alafs) duplication Pathogenic rs786200899 GRCh37 Chromosome 19, 39993644: 39993648
3 DLL3 NM_016941.3(DLL3): c.945_946delAT (p.Ala317Argfs) deletion Pathogenic rs786200900 GRCh38 Chromosome 19, 39505303: 39505304
4 DLL3 NM_016941.3(DLL3): c.945_946delAT (p.Ala317Argfs) deletion Pathogenic rs786200900 GRCh37 Chromosome 19, 39995943: 39995944
5 DLL3 NM_016941.3(DLL3): c.1154G> A (p.Gly385Asp) single nucleotide variant Pathogenic rs104894674 GRCh37 Chromosome 19, 39997739: 39997739
6 DLL3 NM_016941.3(DLL3): c.1154G> A (p.Gly385Asp) single nucleotide variant Pathogenic rs104894674 GRCh38 Chromosome 19, 39507099: 39507099
7 DLL3 NM_016941.3(DLL3): c.1291_1307dup17 (p.Pro437Thrfs) duplication Pathogenic rs786200901 GRCh38 Chromosome 19, 39507236: 39507252
8 DLL3 NM_016941.3(DLL3): c.1291_1307dup17 (p.Pro437Thrfs) duplication Pathogenic rs786200901 GRCh37 Chromosome 19, 39997876: 39997892
9 DLL3 NM_016941.3(DLL3): c.618delC (p.Cys207Alafs) deletion Pathogenic rs786200902 GRCh38 Chromosome 19, 39503023: 39503023
10 DLL3 NM_016941.3(DLL3): c.618delC (p.Cys207Alafs) deletion Pathogenic rs786200902 GRCh37 Chromosome 19, 39993663: 39993663
11 DLL3 NM_016941.3(DLL3): c.712C> T (p.Arg238Ter) single nucleotide variant Pathogenic rs104894675 GRCh37 Chromosome 19, 39994770: 39994770
12 DLL3 NM_016941.3(DLL3): c.712C> T (p.Arg238Ter) single nucleotide variant Pathogenic rs104894675 GRCh38 Chromosome 19, 39504130: 39504130
13 DLL3 NM_016941.3(DLL3): c.1440delG (p.Pro481Argfs) deletion Pathogenic rs786200903 GRCh38 Chromosome 19, 39507385: 39507385
14 DLL3 NM_016941.3(DLL3): c.1440delG (p.Pro481Argfs) deletion Pathogenic rs786200903 GRCh37 Chromosome 19, 39998025: 39998025
15 DLL3 NM_016941.3(DLL3): c.1511G> A (p.Gly504Asp) single nucleotide variant Pathogenic rs104894676 GRCh37 Chromosome 19, 39998096: 39998096
16 DLL3 NM_016941.3(DLL3): c.1511G> A (p.Gly504Asp) single nucleotide variant Pathogenic rs104894676 GRCh38 Chromosome 19, 39507456: 39507456
17 MESP2 NM_001039958.1(MESP2): c.-11G> A single nucleotide variant Likely benign rs139599055 GRCh37 Chromosome 15, 90319578: 90319578
18 MESP2 NM_001039958.1(MESP2): c.-11G> A single nucleotide variant Likely benign rs139599055 GRCh38 Chromosome 15, 89776347: 89776347
19 MESP2 NM_001039958.1(MESP2): c.412G> A (p.Val138Met) single nucleotide variant Benign rs28462216 GRCh38 Chromosome 15, 89776769: 89776769
20 MESP2 NM_001039958.1(MESP2): c.412G> A (p.Val138Met) single nucleotide variant Benign rs28462216 GRCh37 Chromosome 15, 90320000: 90320000
21 MESP2 NM_001039958.1(MESP2): c.498C> G (p.Pro166=) single nucleotide variant Likely benign rs200336355 GRCh38 Chromosome 15, 89776855: 89776855
22 MESP2 NM_001039958.1(MESP2): c.498C> G (p.Pro166=) single nucleotide variant Likely benign rs200336355 GRCh37 Chromosome 15, 90320086: 90320086
23 MESP2 NM_001039958.1(MESP2): c.531G> A (p.Ala177=) single nucleotide variant Benign/Likely benign rs75049807 GRCh38 Chromosome 15, 89776888: 89776888
24 MESP2 NM_001039958.1(MESP2): c.531G> A (p.Ala177=) single nucleotide variant Benign/Likely benign rs75049807 GRCh37 Chromosome 15, 90320119: 90320119
25 MESP2 NM_001039958.1(MESP2): c.558G> A (p.Gln186=) single nucleotide variant Likely benign rs28546919 GRCh38 Chromosome 15, 89776915: 89776915
26 MESP2 NM_001039958.1(MESP2): c.558G> A (p.Gln186=) single nucleotide variant Likely benign rs28546919 GRCh37 Chromosome 15, 90320146: 90320146
27 MESP2 NM_001039958.1(MESP2): c.671C> T (p.Ser224Phe) single nucleotide variant Likely benign rs71647807 GRCh38 Chromosome 15, 89777028: 89777028
28 MESP2 NM_001039958.1(MESP2): c.671C> T (p.Ser224Phe) single nucleotide variant Likely benign rs71647807 GRCh37 Chromosome 15, 90320259: 90320259
29 MESP2 NM_001039958.1(MESP2): c.908T> C (p.Leu303Pro) single nucleotide variant Likely benign rs185706635 GRCh38 Chromosome 15, 89777265: 89777265
30 MESP2 NM_001039958.1(MESP2): c.908T> C (p.Leu303Pro) single nucleotide variant Likely benign rs185706635 GRCh37 Chromosome 15, 90320496: 90320496
31 DLL3 NM_016941.3(DLL3): c.546C> G (p.Ala182=) single nucleotide variant Benign rs8106337 GRCh38 Chromosome 19, 39502951: 39502951
32 DLL3 NM_016941.3(DLL3): c.546C> G (p.Ala182=) single nucleotide variant Benign rs8106337 GRCh37 Chromosome 19, 39993591: 39993591
33 DLL3 NM_016941.3(DLL3): c.1029C> T (p.Pro343=) single nucleotide variant Benign rs2304214 GRCh37 Chromosome 19, 39996027: 39996027
34 DLL3 NM_016941.3(DLL3): c.1029C> T (p.Pro343=) single nucleotide variant Benign rs2304214 GRCh38 Chromosome 19, 39505387: 39505387
35 DLL3 NM_016941.3(DLL3): c.1562C> T (p.Ser521Phe) single nucleotide variant Likely benign rs191149379 GRCh38 Chromosome 19, 39507507: 39507507
36 DLL3 NM_016941.3(DLL3): c.1562C> T (p.Ser521Phe) single nucleotide variant Likely benign rs191149379 GRCh37 Chromosome 19, 39998147: 39998147
37 DLL3 NM_016941.3(DLL3): c.1674-10C> T single nucleotide variant Benign/Likely benign rs116099821 GRCh38 Chromosome 19, 39507820: 39507820
38 DLL3 NM_016941.3(DLL3): c.1674-10C> T single nucleotide variant Benign/Likely benign rs116099821 GRCh37 Chromosome 19, 39998460: 39998460
39 MESP2 NM_001039958.1(MESP2): c.558_569delGGGGCAGGGGCA (p.Gln202_Gly205del) deletion Benign/Likely benign rs56192595 GRCh37 Chromosome 15, 90320146: 90320157
40 MESP2 NM_001039958.1(MESP2): c.558_569delGGGGCAGGGGCA (p.Gln202_Gly205del) deletion Benign/Likely benign rs56192595 GRCh38 Chromosome 15, 89776915: 89776926
41 MESP2 NM_001039958.1(MESP2): c.306C> A (p.His102Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs77473319 GRCh37 Chromosome 15, 90319894: 90319894
42 MESP2 NM_001039958.1(MESP2): c.306C> A (p.His102Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs77473319 GRCh38 Chromosome 15, 89776663: 89776663
43 DLL3 NM_016941.3(DLL3): c.1066C> T (p.Arg356Trp) single nucleotide variant Uncertain significance rs146274789 GRCh37 Chromosome 19, 39996064: 39996064
44 DLL3 NM_016941.3(DLL3): c.1066C> T (p.Arg356Trp) single nucleotide variant Uncertain significance rs146274789 GRCh38 Chromosome 19, 39505424: 39505424
45 MESP2 NM_001039958.1(MESP2): c.*210C> G single nucleotide variant Uncertain significance rs886051548 GRCh37 Chromosome 15, 90321775: 90321775
46 MESP2 NM_001039958.1(MESP2): c.556C> G (p.Gln186Glu) single nucleotide variant Uncertain significance rs776642665 GRCh37 Chromosome 15, 90320144: 90320144
47 MESP2 NM_001039958.1(MESP2): c.556C> G (p.Gln186Glu) single nucleotide variant Uncertain significance rs776642665 GRCh38 Chromosome 15, 89776913: 89776913
48 MESP2 NM_001039958.1(MESP2): c.1080C> T (p.Ala360=) single nucleotide variant Uncertain significance rs762014488 GRCh37 Chromosome 15, 90321451: 90321451
49 MESP2 NM_001039958.1(MESP2): c.1080C> T (p.Ala360=) single nucleotide variant Uncertain significance rs762014488 GRCh38 Chromosome 15, 89778220: 89778220
50 MESP2 NM_001039958.1(MESP2): c.*210C> G single nucleotide variant Uncertain significance rs886051548 GRCh38 Chromosome 15, 89778544: 89778544

Expression for Spondylocostal Dysostosis 1, Autosomal Recessive

Search GEO for disease gene expression data for Spondylocostal Dysostosis 1, Autosomal Recessive.

Pathways for Spondylocostal Dysostosis 1, Autosomal Recessive

Pathways related to Spondylocostal Dysostosis 1, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.22 DLL3 LFNG
2 9.84 HES7 LFNG MESP2

GO Terms for Spondylocostal Dysostosis 1, Autosomal Recessive

Biological processes related to Spondylocostal Dysostosis 1, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.55 DLL3 HES7 LFNG MESP2 PAX1
2 skeletal system development GO:0001501 9.54 DLL3 HES7 PAX1
3 Notch signaling pathway GO:0007219 9.5 DLL3 HES7 MESP2
4 pattern specification process GO:0007389 9.4 LFNG PAX1
5 regulation of somitogenesis GO:0014807 9.26 HES7 LFNG
6 somitogenesis GO:0001756 9.02 DLL3 HES7 LFNG MESP2 PAX1
7 compartment pattern specification GO:0007386 8.96 DLL3 LFNG

Molecular functions related to Spondylocostal Dysostosis 1, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein dimerization activity GO:0046983 8.62 HES7 MESP2

Sources for Spondylocostal Dysostosis 1, Autosomal Recessive

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