SCDO3
MCID: SPN297
MIFTS: 48

Spondylocostal Dysostosis 3, Autosomal Recessive (SCDO3)

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

Aliases & Classifications for Spondylocostal Dysostosis 3, Autosomal Recessive

MalaCards integrated aliases for Spondylocostal Dysostosis 3, Autosomal Recessive:

Name: Spondylocostal Dysostosis 3, Autosomal Recessive 57 74
Spondylocostal Dysostosis 12 53 25 37 15
Spondylocostal Dysostosis, Autosomal Recessive 3 12 13 72
Jarcho-Levin Syndrome 12 25 72
Scdo3 57 74
Scdo 53 25
Dysostosis, Spondylocostal, Autosomal Recessive, Type 3 40
Spondylothoracic Dysostosis 12
Spondylothoracic Dysplasia 12
Dysostosis, Spondylocostal 40
Costovertebral Dysplasia 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
two patients have been independently reported (last curated february 2019)


HPO:

32
spondylocostal dysostosis 3, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0050568
KEGG 37 H00517
MeSH 44 D004413
MedGen 42 C1853296
UMLS 72 C0265343 C1853296

Summaries for Spondylocostal Dysostosis 3, Autosomal Recessive

Genetics Home Reference : 25 Spondylocostal dysostosis is a group of conditions characterized by abnormal development of bones in the spine and ribs. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). Many people with this condition have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae. In addition to spinal abnormalities, some of the rib bones may be fused together or missing. Affected individuals have short, rigid necks and short torsos because of the bone malformations. As a result, people with spondylocostal dysostosis have short bodies but normal-length arms and legs, called short-trunk dwarfism. The spine and rib abnormalities, which are present from birth, cause other signs and symptoms of spondylocostal dysostosis. Infants with this condition have small chests that cannot expand adequately, often leading to life-threatening breathing problems. As the lungs expand in the narrow chest, the muscle that separates the abdomen from the chest cavity (the diaphragm) is forced down and the abdomen is pushed out. The increased pressure in the abdomen can cause a soft out-pouching around the lower abdomen (inguinal hernia), particularly in males with spondylocostal dysostosis. Some people with spondylocostal dysostosis also have a type of birth defect known as a neural tube defect. Neural tube defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Examples of neural tube defects that occur in people with spondylocostal dysostosis include a spinal cord abnormality known as spina bifida and a brain abnormality called a Chiari malformation. Although breathing problems can be fatal early in life, many affected individuals live into adulthood. Spondylocostal dysostosis has often been grouped with a similar condition called spondylothoracic dysostosis, and both are sometimes called Jarcho-Levin syndrome; however, they are now considered distinct conditions.

MalaCards based summary : Spondylocostal Dysostosis 3, Autosomal Recessive, also known as spondylocostal dysostosis, is related to spondylocostal dysostosis 5 and spondylocostal dysostosis 1, autosomal recessive. An important gene associated with Spondylocostal Dysostosis 3, Autosomal Recessive is LFNG (LFNG O-Fucosylpeptide 3-Beta-N-Acetylglucosaminyltransferase), and among its related pathways/superpathways are Notch signaling pathway and Mesodermal Commitment Pathway. Affiliated tissues include bone, brain and lung, and related phenotypes are scoliosis and kyphosis

Disease Ontology : 12 A dysostosis that results in abnormal development located in vertebrae or located in ribs. The bones of the spine do not develop properly, which causes them to be misshapen and abnormally joined together.

NIH Rare Diseases : 53 Spondylocostal dysostosis is a group of conditions characterized by abnormal development of the bones in the spine and ribs. In the spine, the vertebrae are misshapen and fused. Many people with this condition have an abnormal side-to-side curvature of the spine (scoliosis). The ribs may be fused together or missing. These bone malformations lead to short, rigid necks and short midsections. Infants with spondylocostal dysostosis have small, narrow chests that cannot fully expand. This can lead to life-threatening breathing problems. Males with this condition are at an increased risk for inguinal hernia, where the diaphragm is pushed down, causing the abdomen to bulge out. There are several types of spondylocostal dysostosis. These types have similar features and are distinguished by their genetic cause and how they are inherited, autosomal recessive or autosomal dominant . Some of the autosomal recessive types of spondylocostal dysostosis are called "Jarcho-Levin syndrome", a term that is more often used as a synonym for a similar condition known as "spondylothoracic dysostosis". Treatment is symptomatic and supportive and may include respiratory support and surgery to correct inguinal hernia and scoliosis.

KEGG : 37
Spondylocostal dysostosis (SCDO) is a group of disorders characterized by vertebral defects along the entire spinal column with rib fusions and deletions. SCD arises from disturbed somite segmentation during embryonic development due to mutations in Notch pathway genes.

UniProtKB/Swiss-Prot : 74 Spondylocostal dysostosis 3, 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.

Wikipedia : 75 Spondylocostal dysostosis is a rare, heritable axial skeleton growth disorder. It is characterized by... more...

More information from OMIM: 609813 PS277300

Related Diseases for Spondylocostal Dysostosis 3, 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 3, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 88)
# Related Disease Score Top Affiliating Genes
1 spondylocostal dysostosis 5 33.2 TBX6 HES7
2 spondylocostal dysostosis 1, autosomal recessive 31.4 MESP2 LFNG HES7 DLL3
3 spondylocostal dysostosis, autosomal recessive 28.3 RIPPLY2 MESP2 LFNG HES7 DLL3
4 dysostosis 27.9 TBX6 RIPPLY2 MESP2 LFNG HES7 DLL3
5 scoliosis 27.8 TBX6 RIPPLY2 MESP2 LFNG HES7 DLL3
6 spondylocostal dysostosis 6, autosomal recessive 12.9
7 spondylocostal dysostosis 4, autosomal recessive 12.8
8 hydrocephalus, sprengel anomaly, and costovertebral dysplasia 12.7
9 spondylocostal dysostosis 2 12.6
10 spondylocostal dysostosis 4 12.6
11 spondylocostal dysostosis-hypospadias-intellectual disability syndrome 12.4
12 spondylocostal dysostosis 3 11.6
13 spondylocostal dysostosis 1 11.6
14 neural tube defects 10.8
15 respiratory failure 10.7
16 hydrocephalus 10.6
17 congenital hydrocephalus 10.6
18 diastematomyelia 10.5
19 split spinal cord malformation 10.5
20 syringomyelia, noncommunicating isolated 10.4
21 vesicoureteral reflux 1 10.4
22 chiari malformation type ii 10.4
23 syringomyelia 10.4
24 lung disease 10.4
25 chiari malformation 10.4
26 spina bifida occulta 10.3
27 meckel diverticulum 10.3
28 osteoporosis 10.3
29 pancreas, annular 10.3
30 anus, imperforate 10.3
31 duodenal atresia 10.3
32 wilms tumor 5 10.3
33 bone mineral density quantitative trait locus 8 10.3
34 bone mineral density quantitative trait locus 15 10.3
35 pulmonary hypertension 10.3
36 myelomeningocele 10.3
37 intestinal atresia 10.3
38 meningocele 10.3
39 placenta praevia 10.3
40 synostosis 10.3
41 hypothyroidism 10.3
42 heart septal defect 10.3
43 atrial heart septal defect 10.3
44 holoprosencephaly 10.3
45 polyhydramnios 10.3
46 skeletal dysplasias 10.3
47 back pain 10.3
48 overgrowth syndrome 10.3
49 diaphragmatic hernia, congenital 10.2
50 robinow syndrome, autosomal recessive 1 10.2

Graphical network of the top 20 diseases related to Spondylocostal Dysostosis 3, Autosomal Recessive:



Diseases related to Spondylocostal Dysostosis 3, Autosomal Recessive

Symptoms & Phenotypes for Spondylocostal Dysostosis 3, Autosomal Recessive

Human phenotypes related to Spondylocostal Dysostosis 3, Autosomal Recessive:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 scoliosis 32 HP:0002650
2 kyphosis 32 HP:0002808
3 short stature 32 HP:0004322
4 vertebral segmentation defect 32 HP:0003422
5 rib fusion 32 HP:0000902
6 slender finger 32 HP:0001238
7 hypoplasia of the odontoid process 32 HP:0003311
8 supernumerary vertebral ossification centers 32 HP:0004598

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
kyphosis
hypoplastic odontoid process
multiple vertebral anomalies
'pebble-beach' appearance of vertebral bodies
multiple vertebral ossification centers
more
Chest Ribs Sternum Clavicles And Scapulae:
fused ribs

Skeletal Limbs:
normal long bones

Growth Height:
short stature

Skeletal Pelvis:
normal pelvis

Clinical features from OMIM:

609813

MGI Mouse Phenotypes related to Spondylocostal Dysostosis 3, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.91 DLL3 HES7 LFNG MESP2 NOTCH1 RIPPLY2
2 growth/size/body region MP:0005378 9.87 DLL3 HES7 LFNG MESP2 NOTCH1 RIPPLY2
3 limbs/digits/tail MP:0005371 9.73 DLL3 HES7 LFNG MESP2 RIPPLY2 TBX6
4 mortality/aging MP:0010768 9.7 DLL3 HES7 LFNG MESP2 NOTCH1 RIPPLY2
5 muscle MP:0005369 9.26 DLL3 MESP2 NOTCH1 RIPPLY2
6 skeleton MP:0005390 9.17 DLL3 HES7 LFNG MESP2 NOTCH1 RIPPLY2

Drugs & Therapeutics for Spondylocostal Dysostosis 3, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spondylocostal Dysostosis 3, Autosomal Recessive

Genetic Tests for Spondylocostal Dysostosis 3, Autosomal Recessive

Anatomical Context for Spondylocostal Dysostosis 3, Autosomal Recessive

MalaCards organs/tissues related to Spondylocostal Dysostosis 3, Autosomal Recessive:

41
Bone, Brain, Lung, Spinal Cord, Kidney, Spleen

The Foundational Model of Anatomy Ontology organs/tissues related to Spondylocostal Dysostosis 3, Autosomal Recessive:

19
Vertebrae, Ribs

Publications for Spondylocostal Dysostosis 3, Autosomal Recessive

Articles related to Spondylocostal Dysostosis 3, Autosomal Recessive:

(show top 50) (show all 150)
# Title Authors PMID Year
1
Identification of novel LFNG mutations in spondylocostal dysostosis. 38 8 71
30531807 2019
2
Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype. 38 8 71
16385447 2006
3
Spondylocostal Dysostosis, Autosomal Recessive 38 71
20301771 2009
4
Mutated MESP2 causes spondylocostal dysostosis in humans. 38 8
15122512 2004
5
Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis. 38
31015262 2019
6
Phenotypic heterogeneity of kyphoscoliosis with vertebral and rib defects: a case series. 38
30921094 2019
7
Spondylocostal Dysostosis (Jarcho-Levin Syndrome) in an Adult Patient with Consanguineous Parents, in Long-Term Follow-Up. 38
30448585 2019
8
A Cryptic Cause of Cardiac Arrest. 38
30420309 2019
9
Screening of known disease genes in congenital scoliosis. 38
30196550 2018
10
Spondylocostal Dysostosis (Jarcho Levin Syndrome). 38
29270795 2018
11
Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients. 38
29459493 2018
12
Homozygous DMRT2 variant associates with severe rib malformations in a newborn. 38
29681102 2018
13
Spondylocostal Dysostosis: A Literature Review and Case Report with Long-Term Follow-Up of a Conservatively Managed Patient. 38
29765785 2018
14
Response to Lefebvre et al. 38
28990171 2017
15
Lipomeningomyelocele with Fatty Filum Terminale in a Patient with Jarcho-Levin Syndrome: A Rare Association Requiring Special Attention. 38
29675085 2017
16
Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis. 38
27861764 2017
17
The developmental biology of genetic Notch disorders. 38
28512196 2017
18
Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis. 38
28054739 2017
19
Combined use of Neurally Adjusted Ventilatory Assist (NAVA) and Vertical Expandable Prostethic Titanium Rib (VEPTR) in a patient with Spondylocostal dysostosis and associated bronchomalacia. 38
28196820 2017
20
Congenital hemangioma in spondylocostal dysostosis: a novel association. 38
28300884 2016
21
Mind the gap: an unusual case of a cervical lipomyelocele. 38
27594964 2016
22
[Spondylocostal dysostosis and acute cholangitis in pediatrics emergency room]. 38
29421389 2016
23
Fetus with Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of a Novel Association and Review of the Phenotype. 38
26367183 2016
24
Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1. 38
26801181 2016
25
The many roles of Notch signaling during vertebrate somitogenesis. 38
25483003 2016
26
Spondylocostal dysostosis associated with right-sided polythelia, right-sided rib deformity and meningocoele: Case report with review of literature. 38
26962344 2015
27
Spondylocostal dysostosis (Jarcho-Levine syndrome) associated with occult spinal dysraphism: Report of two cases. 38
26167215 2015
28
Expanding the phenotype of spondylospinal thoracic dysostosis (the Turkel-Chen-Johnson syndrome). 38
25304117 2015
29
Correction: Novel ENU-Induced Mutation in Tbx6 Causes Dominant Spondylocostal Dysostosis-Like Vertebral Malformations in the Rat. 38
26222705 2015
30
Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs. 38
25659135 2015
31
Novel ENU-Induced Mutation in Tbx6 Causes Dominant Spondylocostal Dysostosis-Like Vertebral Malformations in the Rat. 38
26090680 2015
32
Management of thoracic insufficiency syndrome in patients with Jarcho-Levin syndrome using VEPTRs (vertical expandable prosthetic titanium ribs). 38
25378514 2014
33
Spinal and pelvic corrections in a patient with spondylocostal dysplasia syndrome and hemimyelomeningocele. 38
25323186 2014
34
Spondylocostal dysostosis with lipomyelomeningocele: Case report and review of the literature. 38
25624929 2014
35
Spondylocostal dysostosis with tetralogy of Fallot and herniation of the spleen through the diaphragm. 38
24666313 2014
36
Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus. 38
23897666 2013
37
Notch signaling in skeletal health and disease. 38
23554451 2013
38
Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6. 38
23335591 2013
39
Spatiotemporal disorder in the axial skeleton development of the Mesp2-null mouse: a model of spondylocostal dysostosis and spondylothoracic dysostosis. 38
23238123 2013
40
A rare case of fetal spondylocostal dysostosis - prenatal diagnosis and perinatal care in a patient with multiple large leiomyomas. 38
23599829 2013
41
Spondylocostal dysostosis associated with type I split cord malformation and double nipple on one side: a case report. 38
23546915 2013
42
Congenital disorders of glycosylation. Part II. Defects of protein O-glycosylation. 38
24051442 2013
43
Brothers with hypospadias, vertebral segmentation defects, and intellectual disability: new syndrome? 38
23166036 2012
44
Notch signaling in human development and disease. 38
22306179 2012
45
Notch regulation of bone development and remodeling and related skeletal disorders. 38
22002679 2012
46
Genetic and clinical profiles of spondylocostal dysostosis patients in Taiwan. 38
22052723 2011
47
The mouse notches up another success: understanding the causes of human vertebral malformation. 38
21667129 2011
48
Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis. 38
21147753 2011
49
Clinical and radiological distinction between spondylothoracic dysostosis (Lavy-Moseley syndrome) and spondylocostal dysostosis (Jarcho-Levin syndrome). 38
21174082 2011
50
Two novel missense mutations in HAIRY-AND-ENHANCER-OF-SPLIT-7 in a family with spondylocostal dysostosis. 38
20087400 2010

Variations for Spondylocostal Dysostosis 3, Autosomal Recessive

ClinVar genetic disease variations for Spondylocostal Dysostosis 3, Autosomal Recessive:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 LFNG NM_001040168.2(LFNG): c.564C> A (p.Phe188Leu) single nucleotide variant Pathogenic rs104894024 7:2564935-2564935 7:2525301-2525301
2 LFNG NM_001040168.2(LFNG): c.601G> A (p.Asp201Asn) single nucleotide variant Pathogenic 7:2565067-2565067 7:2525433-2525433
3 LFNG NM_001040168.2(LFNG): c.372del (p.Lys124fs) deletion Pathogenic 7:2559867-2559867 7:2520233-2520233
4 LFNG NM_001040168.2(LFNG): c.715C> T (p.Arg239Trp) single nucleotide variant Uncertain significance 7:2565181-2565181 7:2525547-2525547
5 LFNG NM_001040168.2(LFNG): c.1013A> T (p.Glu338Val) single nucleotide variant Uncertain significance 7:2566495-2566495 7:2526861-2526861
6 LFNG NM_001040168.2(LFNG): c.643G> A (p.Ala215Thr) single nucleotide variant Uncertain significance rs1160316709 7:2565109-2565109 7:2525475-2525475
7 LFNG NM_001040168.2(LFNG): c.653C> T (p.Pro218Leu) single nucleotide variant Uncertain significance rs148460430 7:2565119-2565119 7:2525485-2525485
8 LFNG NM_001040168.2(LFNG): c.723C> T (p.Ser241=) single nucleotide variant Likely benign rs115678269 7:2565189-2565189 7:2525555-2525555
9 LFNG NM_001040168.2(LFNG): c.482-4A> G single nucleotide variant Benign rs62444250 7:2564849-2564849 7:2525215-2525215

UniProtKB/Swiss-Prot genetic disease variations for Spondylocostal Dysostosis 3, Autosomal Recessive:

74
# Symbol AA change Variation ID SNP ID
1 LFNG p.Phe188Leu VAR_025850 rs104894024

Copy number variations for Spondylocostal Dysostosis 3, Autosomal Recessive from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 96229 15 86900000 92100000 Copy number MESP2 Spondylocostal dysostosis
2 116536 17 6800000 11200000 Copy number HES7 Spondylocostal dysostosis
3 128868 19 43400000 47800000 Copy number DLL3 Spondylocostal dysostosis
4 223467 7 2100000 4500000 Copy number LFNG Spondylocostal dysostosis

Expression for Spondylocostal Dysostosis 3, Autosomal Recessive

Search GEO for disease gene expression data for Spondylocostal Dysostosis 3, Autosomal Recessive.

Pathways for Spondylocostal Dysostosis 3, Autosomal Recessive

Pathways related to Spondylocostal Dysostosis 3, Autosomal Recessive according to KEGG:

37
# Name Kegg Source Accession
1 Notch signaling pathway hsa04330

GO Terms for Spondylocostal Dysostosis 3, Autosomal Recessive

Biological processes related to Spondylocostal Dysostosis 3, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.8 TBX6 RIPPLY2 NOTCH1 HES7
2 multicellular organism development GO:0007275 9.8 TBX6 RIPPLY2 NOTCH1 MESP2 LFNG HES7
3 determination of left/right symmetry GO:0007368 9.55 RIPPLY2 NOTCH1
4 positive regulation of Notch signaling pathway GO:0045747 9.54 NOTCH1 LFNG
5 regulation of neurogenesis GO:0050767 9.52 NOTCH1 HES7
6 mesoderm development GO:0007498 9.51 TBX6 HES7
7 negative regulation of neurogenesis GO:0050768 9.48 NOTCH1 DLL3
8 cell fate specification GO:0001708 9.46 TBX6 NOTCH1
9 post-anal tail morphogenesis GO:0036342 9.43 RIPPLY2 HES7
10 regulation of Notch signaling pathway GO:0008593 9.4 NOTCH1 LFNG
11 somite rostral/caudal axis specification GO:0032525 9.37 TBX6 RIPPLY2
12 Notch signaling pathway GO:0007219 9.35 RIPPLY2 NOTCH1 MESP2 HES7 DLL3
13 compartment pattern specification GO:0007386 9.33 NOTCH1 LFNG DLL3
14 regulation of somitogenesis GO:0014807 9.32 NOTCH1 LFNG
15 somitogenesis GO:0001756 9.02 RIPPLY2 MESP2 LFNG HES7 DLL3

Molecular functions related to Spondylocostal Dysostosis 3, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Notch binding GO:0005112 8.62 NOTCH1 DLL3

Sources for Spondylocostal Dysostosis 3, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
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32 HPO
33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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