Spondylocostal Dysostosis

Mendelian MONDO:0000359 Pathograph 3 Show in embeddings browser Vertebral Malformation Disorders

Spondylocostal dysostosis (SCDO) is a congenital axial-skeleton malformation disorder defined radiographically as multiple segmentation defects of the vertebrae in combination with rib abnormalities. It arises from disruption of somitogenesis: the vertebrae and ribs are serially repeated derivatives of the somites, which are produced one pair at a time by the segmentation clock — a coupled Notch/Wnt/FGF oscillator in the presomitic mesoderm — so a lesion in the clock or its Notch components perturbs many segments at once. Autosomal recessive SCDO is caused by biallelic variants in the Notch-pathway genes DLL3 (SCDO1), MESP2 (SCDO2), LFNG (SCDO3), and HES7 (SCDO4), as well as RIPPLY2 and TBX6. Clinically it presents with a short trunk, short neck, usually mild non-progressive scoliosis, and — in severely affected neonates — a small thorax with restrictive respiratory compromise. SCDO is the prototype conformer of the axial-skeleton serial-homology mechanism module.

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1
Inheritance
3
Pathophys.
9
Phenotypes
3
Pathograph
2
Medical Actions
6
Subtypes
1
References
🏷

Classifications

ISDS Skeletal Nosology
dysostoses with predominant vertebral and costal involvement
👪

Inheritance

1
Autosomal Recessive
SCDO is most commonly inherited in an autosomal recessive manner, caused by biallelic pathogenic variants in segmentation-clock / Notch-pathway genes.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"Identification of biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 can confirm the diagnosis of autosomal recessive SCDO."
GeneReviews establishes autosomal recessive inheritance and the causative Notch-pathway gene panel for SCDO.
◆

Subtypes

6
SCDO1 (DLL3-related) MONDO:0020692
DLL3 hgnc:2909 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in DLL3 (hgnc:2909). hgnc:2909 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Recessive'}
SCDO1 (OMIM:277300) is caused by biallelic pathogenic variants in DLL3, which encodes a Notch ligand acting in the presomitic-mesoderm segmentation clock. It was the first molecularly solved form of SCDO and produces a consistent, distinctive pattern of abnormal vertebral segmentation affecting the entire spine. Note that MONDO carries "spondylothoracic dysostosis" as a RELATED synonym on this DLL3 term; that synonym is a named-entity-confusion hazard, because the classic symmetric "crab-like-rib" STD entity is MESP2-related (see the SCDO2 subtype).
Show evidence (2 references)
PMID:10742114 SUPPORT Human Clinical
"Here we have cloned and sequenced human DLL3 to evaluate it as a candidate gene for SD and identified mutations in three autosomal recessive SD families."
Establishes biallelic DLL3 variants as a cause of autosomal recessive spondylocostal dysostosis, the lesion that defines the SCDO1 subtype.
PMID:16385447 SUPPORT Human Clinical
"Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2)."
Anchors the numbered subtype nomenclature, assigning DLL3 to SCDO1 and MESP2 to SCDO2.
SCDO2 (MESP2-related; includes spondylothoracic dysostosis / Puerto Rican Jarcho-Levin) MONDO:0012097
MESP2 hgnc:29659 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in MESP2 (hgnc:29659). hgnc:29659 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Recessive'}
SCDO2 (OMIM:608681) is caused by biallelic pathogenic variants in MESP2, a bHLH transcription factor that translates segmentation-clock oscillations into somite-boundary and rostrocaudal-polarity specification. This is the subtype that carries the spondylothoracic dysostosis (STD) / classic Puerto Rican "Jarcho-Levin syndrome" phenotype — symmetric, posteriorly fused "crab-like" ribs with a shortened trunk and early-childhood respiratory compromise — attributable to a MESP2 E103X founder mutation. Recording that identity here is the dismech-side mitigation for the ontology gap in issue #4957: MONDO has no distinct STD class, and the string "spondylothoracic dysostosis" appears as a synonym on the DLL3 (SCDO1) and TBX6 (SCDO5) terms rather than on this MESP2 term.
Show evidence (3 references)
PMID:15122512 SUPPORT Human Clinical
"Using a genomewide scanning strategy in one consanguineous family with two affected children, we demonstrated linkage to 15q21.3-15q26.1 and furthermore identified a 4-bp duplication mutation in the human MESP2 gene that codes for a basic helix-loop-helix transcription factor."
Original identification of biallelic MESP2 variants as a cause of spondylocostal dysostosis, defining the SCDO2 subtype.
PMID:18485326 SUPPORT Human Clinical
"Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is an autosomal-recessive disorder characterized by abnormal vertebral segmentation and defects affecting spine formation, with complete bilateral fusion of the ribs at the costovertebral junction producing a..."
Defines the symmetric "crab-like"-rib STD/Jarcho-Levin phenotype that this subtype carries, distinguishing it from the chaotic, asymmetric malsegmentation of the other SCDO subtypes.
PMID:18485326 SUPPORT Human Clinical
"Our findings suggest a founder-effect mutation in the MESP2 gene as a major cause of the classical Puerto Rican form of STD/JLS."
Grounds the STD/Jarcho-Levin eponym on MESP2 (i.e., SCDO2) rather than on the DLL3 or TBX6 terms that carry the STD synonym in MONDO, and supports the Puerto Rican geography annotation.
SCDO3 (LFNG-related) MONDO:0012349
LFNG hgnc:6560 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in LFNG (hgnc:6560). hgnc:6560 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Recessive'}
SCDO3 (OMIM:609813) is caused by biallelic pathogenic variants in LFNG (LUNATIC FRINGE), a glycosyltransferase that modifies Notch receptors and is required for correct oscillation of the segmentation clock. The reported vertebral phenotype is severe. GeneReviews notes that neurologic problems are a management consideration specifically in LFNG-related SCDO.
Show evidence (2 references)
PMID:16385447 SUPPORT Human Clinical
"Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD."
Original identification of LFNG as the third autosomal recessive SCDO gene, defining the SCDO3 subtype.
PMID:20301771 SUPPORT Human Clinical
"Standard treatment of neurologic problems associated with LFNG-related SCDO."
GeneReviews singles out LFNG-related SCDO as the form with neurologic problems requiring management.
SCDO4 (HES7-related) MONDO:0013366
HES7 hgnc:15977 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in HES7 (hgnc:15977). hgnc:15977 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Recessive'}
SCDO4 (OMIM:613686) is caused by biallelic pathogenic variants in HES7, the Notch-driven transcriptional repressor that generates the oscillation of the segmentation clock itself. HES7-related disease is distinguished from the other SCDO subtypes by co-occurring laterality defects (dextrocardia with situs inversus) and neural tube malformations, consistent with an additional role outside somitogenesis.
Show evidence (2 references)
PMID:23897666 SUPPORT Human Clinical
"We found that both individuals were homozygous for the same mutation in HES7, and that this mutation caused a significant reduction of HES7 protein function; HES7 mutation causes SCD4."
Explicitly assigns HES7 to the SCDO4 subtype and demonstrates loss of HES7 function in affected individuals.
PMID:23897666 SUPPORT Human Clinical
"In conclusion, it appears that mutation of HES7 is uniquely associated with defects in vertebral, heart and neural tube formation, and this observation will help provide a discriminatory diagnostic guide in patients with SCD, as well as inform molecular genetic testing."
Supports the laterality and neural tube findings as the features that differentiate SCDO4 from the other subtypes.
SCDO5 (TBX6-related) MONDO:0007389
TBX6 hgnc:11605 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in TBX6 (hgnc:11605). hgnc:11605 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Dominant', 'description': 'The originally described SCDO5 family showed autosomal dominant transmission of a TBX6 stoploss variant acting by haploinsufficiency. GeneReviews treats this as the exception rather than the rule, noting it was reported in a single three-generation family.', 'evidence': [{'reference': 'PMID:23335591', 'reference_title': 'Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.', 'supports': 'SUPPORT', 'evidence_source': 'HUMAN_CLINICAL', 'snippet': 'This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.', 'explanation': 'Original report establishing autosomal dominant transmission for TBX6-related SCDO.'}]} {'name': 'Autosomal Recessive', 'description': 'TBX6 is also listed among the genes in which biallelic pathogenic variants cause autosomal recessive SCDO, so SCDO5 is not exclusively dominant. This block records the recessive mode alongside the dominant one rather than leaving it in the subtype description, where it is not queryable.', 'evidence': [{'reference': 'PMID:20301771', 'reference_title': 'Spondylocostal Dysostosis, Autosomal Recessive.', 'supports': 'SUPPORT', 'evidence_source': 'HUMAN_CLINICAL', 'snippet': 'SCDO caused by biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 is inherited in an autosomal recessive manner.', 'explanation': 'GeneReviews names TBX6 among the genes whose biallelic variants produce autosomal recessive SCDO, which is the basis for recording a recessive mode on the TBX6-anchored SCDO5 subtype.'}]}
SCDO5 (OMIM:122600) is caused by pathogenic variants in TBX6, the T-box transcription factor that patterns the presomitic mesoderm at the determination wavefront. Unlike SCDO1-SCDO4, SCDO5 was first described with autosomal dominant transmission (a stoploss variant acting by haploinsufficiency), although GeneReviews also lists TBX6 among the genes in which biallelic variants confirm autosomal recessive SCDO. Compound TBX6 null-plus-hypomorphic dosage insufficiency is modeled separately in the TBX6-Associated_Congenital_Scoliosis entry. MONDO carries "spondylothoracic dysostosis" as an EXACT synonym on this TBX6 term, which is the specific mis-resolution hazard described in issue #4957 — the STD entity is MESP2-related (SCDO2), not TBX6-related.
Show evidence (2 references)
PMID:23335591 SUPPORT Human Clinical
"Here, we have used exome capture and next-generation sequencing to identify a stoploss mutation in TBX6 that segregates with disease in two generations of one family."
Original identification of TBX6 as an SCDO gene, defining the SCDO5 subtype.
PMID:23335591 SUPPORT Human Clinical
"This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals."
Supports the autosomal dominant inheritance that distinguishes SCDO5 from the recessive SCDO1-SCDO4 subtypes.
SCDO6 (RIPPLY2-related) MONDO:0014694
RIPPLY2 hgnc:21390 HUGO Gene Nomenclature Committee (hgnc) Relation: this subtype is caused by variation in this gene This subtype is caused by variation in RIPPLY2 (hgnc:21390). hgnc:21390 is a gene from the HUGO Gene Nomenclature Committee. {'name': 'Autosomal Recessive'}
SCDO6 (OMIM:616566) is caused by biallelic pathogenic variants in RIPPLY2, which acts with MESP2 to establish somite rostrocaudal polarity. Reported individuals have cervical- and thoracic-predominant vertebral body malformations with limited rib involvement, and myelopathy from congenital cervical spine malformation is a recognized complication.
Show evidence (2 references)
PMID:25343988 SUPPORT Human Clinical
"We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition."
Report that first associated compound heterozygous RIPPLY2 variants with segmentation defects of the vertebrae, the basis of the SCDO6 subtype. This is the paper's own concluding sentence, which names RIPPLY2 explicitly; it replaces a generic SDV-background sentence that never mentioned the gene and so could not license the association claim.
PMID:33410135 SUPPORT Human Clinical
"All patients had multiple vertebral body malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae."
Confirms biallelic RIPPLY2 variants as the SCDO6 lesion and describes the cervical-predominant vertebral phenotype with myelopathy.
⚙

Pathophysiology

3
Segmentation Clock Gene Disruption
Biallelic loss-of-function variants in Notch-pathway and segmentation-clock genes (DLL3, MESP2, LFNG, HES7, TBX6; also RIPPLY2) disrupt the oscillatory Notch signaling that drives the segmentation clock in the presomitic mesoderm. Proper regulation of Notch signaling is an absolute requirement for correct patterning of the axial skeleton.
Presomitic (Paraxial) Mesoderm Cell CL:0011007 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Presomitic (Paraxial) Mesoderm Cell, annotated with paraxial cell (CL:0011007). CL:0011007 is a cell type from the Cell Ontology.
DLL3 hgnc:2909 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves DLL3 (hgnc:2909). hgnc:2909 is a gene from the HUGO Gene Nomenclature Committee. MESP2 hgnc:29659 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves MESP2 (hgnc:29659). hgnc:29659 is a gene from the HUGO Gene Nomenclature Committee. LFNG hgnc:6560 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves LFNG (hgnc:6560). hgnc:6560 is a gene from the HUGO Gene Nomenclature Committee. HES7 hgnc:15977 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves HES7 (hgnc:15977). hgnc:15977 is a gene from the HUGO Gene Nomenclature Committee. TBX6 hgnc:11605 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves TBX6 (hgnc:11605). hgnc:11605 is a gene from the HUGO Gene Nomenclature Committee. RIPPLY2 hgnc:21390 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves RIPPLY2 (hgnc:21390). hgnc:21390 is a gene from the HUGO Gene Nomenclature Committee.
Somitogenesis GO:0001756 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Somitogenesis (GO:0001756). GO:0001756 is a biological process from the Gene Ontology. ⚠ ABNORMAL Notch Signaling Pathway GO:0007219 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Notch Signaling Pathway (GO:0007219). GO:0007219 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Disrupted Somite Formation Loss of Notch-driven clock oscillation corrupts periodic somite formation.
Show evidence (2 references)
PMID:16385447 SUPPORT Human Clinical
"These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease."
Identifies the SCDO genes (DLL3, MESP2, LFNG) as Notch-pathway components, the molecular trigger of the disorder.
PMID:20301771 SUPPORT Human Clinical
"Identification of biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 can confirm the diagnosis of autosomal recessive SCDO."
Enumerates the segmentation-clock / Notch-pathway genes whose biallelic variants cause SCDO.
Disrupted Somite Formation
Loss of clock oscillation and wavefront positioning corrupts the periodic formation of somite boundaries, so somites form with abnormal timing, number, or rostrocaudal polarity. The metameric template from which the vertebrae and ribs derive is therefore mis-specified.
Presomitic (Paraxial) Mesoderm Cell CL:0011007 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Presomitic (Paraxial) Mesoderm Cell, annotated with paraxial cell (CL:0011007). CL:0011007 is a cell type from the Cell Ontology.
Segmentation GO:0035282 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Segmentation (GO:0035282). GO:0035282 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Vertebral and Rib Malsegmentation Mis-specified somites give rise to malsegmented vertebrae and ribs.
Show evidence (2 references)
PMID:16385447 SUPPORT Human Clinical
"The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis."
States that SCDO arises from disrupted somitogenesis, the central effector step.
PMID:17965051 SUPPORT Model Organism
"The FGF pathway establishes a posterior-to-anterior signaling gradient in the presomitic mesoderm (PSM), which controls cell maturation and is involved in the positioning of segmental boundaries."
Describes the PSM wavefront that positions segmental boundaries, the mechanism whose disruption mis-forms somites. Evidence source is MODEL_ORGANISM (mouse).
Vertebral and Rib Malsegmentation
Because the vertebrae and ribs are serially homologous somite derivatives, the mis-segmentation manifests as a coordinated multi-segment malformation bundle: multiple vertebral segmentation defects (hemivertebrae, fused/block vertebrae) together with rib abnormalities, producing a short trunk and, in severe disease, a small thorax with respiratory compromise.
Chondrocyte CL:0000138 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Chondrocyte (CL:0000138). CL:0000138 is a cell type from the Cell Ontology. Osteoblast CL:0000062 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Osteoblast (CL:0000062). CL:0000062 is a cell type from the Cell Ontology.
Embryonic Skeletal System Morphogenesis GO:0048704 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Embryonic Skeletal System Morphogenesis (GO:0048704). GO:0048704 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (2 references)
PMID:20301771 SUPPORT Human Clinical
"multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs"
Defines the serially homologous axial bundle — multiple vertebral segmentation defects together with rib abnormalities.
PMID:29765785 SUPPORT Human Clinical
"Patients with spondylocostal dysostosis (SCD) have congenital spine and rib deformities associated with frequently severe thoracic insufficiency and respiratory compromise."
Documents combined congenital spine and rib deformities with thoracic insufficiency, the clinical consequence.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Spondylocostal Dysostosis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Cardiovascular 1
Pulmonary Hypertension Pulmonary arterial hypertension HP:0002092 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary hypertension, annotated with Pulmonary arterial hypertension (HP:0002092). HP:0002092 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"there is a possibility that pulmonary hypertension may eventually impact cardiac function"
GeneReviews notes that restricted pulmonary capacity in severe SCDO can lead to pulmonary hypertension affecting cardiac function.
Digestive 1
Inguinal Hernia HP:0000023 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Inguinal hernia (HP:0000023). HP:0000023 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"Males with SCDO appear to be at increased risk for inguinal hernia."
GeneReviews documents an increased risk of inguinal hernia in males with SCDO.
Head and Neck 1
Short Neck HP:0000470 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Short neck (HP:0000470). HP:0000470 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"short neck"
Short neck is a characteristic clinical feature of SCDO.
Musculoskeletal 4
Multiple Vertebral Segmentation Defects Hemivertebrae HP:0002937 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hemivertebrae (HP:0002937). HP:0002937 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs"
SCDO is defined by multiple vertebral segmentation defects.
Vertebral Fusion HP:0002948 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vertebral fusion (HP:0002948). HP:0002948 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs"
Vertebral fusion is among the multiple vertebral segmentation defects of SCDO.
Rib Abnormalities Abnormal rib morphology HP:0000772 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal rib morphology (HP:0000772). HP:0000772 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs"
Rib abnormalities are a defining component of SCDO.
Scoliosis HP:0002650 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Scoliosis (HP:0002650). HP:0002650 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"non-progressive mild scoliosis in most affected individuals"
Mild non-progressive scoliosis occurs in most individuals with SCDO.
Respiratory 1
Respiratory Insufficiency HP:0002093 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory insufficiency (HP:0002093). HP:0002093 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"Respiratory function in neonates with severe disease may be compromised by reduced size of the thorax."
A small thorax can compromise neonatal respiratory function in severe SCDO.
Growth 1
Disproportionate Short-Trunk Short Stature HP:0003521 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Disproportionate short-trunk short stature (HP:0003521). HP:0003521 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"a short trunk in proportion to height"
SCDO is characterized by a short trunk in proportion to height.
💊

Medical Actions

2
Scoliosis Surgical Management
Action: orthopedic surgical procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is orthopedic surgical procedure (NCIT:C16186). NCIT:C16186 is a clinical intervention from the NCI Thesaurus. Ontology label: Orthopedic Surgical Procedure NCIT:C16186
Surgical intervention for significant scoliosis, including external bracing and growth-friendly instrumentation such as a vertical expandable prosthetic titanium rib (VEPTR) to expand thoracic volume.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"Surgical intervention may be necessary when scoliosis is significant"
Significant scoliosis in SCDO may require surgical management.
Respiratory Support
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
Respiratory support, including intensive care, for the minority of individuals with acute respiratory distress or chronic respiratory failure.
Show evidence (1 reference)
PMID:20301771 SUPPORT Human Clinical
"Respiratory support, including intensive care, is provided as needed"
Respiratory support is provided for severe SCDO with respiratory compromise.
📊

Prevalence

1
General
Unknown Unknown
SCDO is a rare disorder documented mainly through case reports, small cohorts, and molecularly characterized families rather than formal population-prevalence studies; autosomal recessive forms are more frequent in consanguineous populations.
{ }

Source YAML

click to show 
name: Spondylocostal Dysostosis
creation_date: "2026-06-28T00:00:00Z"
category: Mendelian
description: >-
  Spondylocostal dysostosis (SCDO) is a congenital axial-skeleton malformation
  disorder defined radiographically as multiple segmentation defects of the
  vertebrae in combination with rib abnormalities. It arises from disruption of
  somitogenesis: the vertebrae and ribs are serially repeated derivatives of the
  somites, which are produced one pair at a time by the segmentation clock — a
  coupled Notch/Wnt/FGF oscillator in the presomitic mesoderm — so a lesion in
  the clock or its Notch components perturbs many segments at once. Autosomal
  recessive SCDO is caused by biallelic variants in the Notch-pathway genes DLL3
  (SCDO1), MESP2 (SCDO2), LFNG (SCDO3), and HES7 (SCDO4), as well as RIPPLY2 and
  TBX6. Clinically it presents with a short trunk, short neck, usually mild
  non-progressive scoliosis, and — in severely affected neonates — a small
  thorax with restrictive respiratory compromise. SCDO is the prototype
  conformer of the axial-skeleton serial-homology mechanism module.
synonyms:
- Jarcho-Levin syndrome
- spondylothoracic dysostosis
- spondylocostal dysplasia
notes: >-
  The eponym "Jarcho-Levin syndrome" is an umbrella historically applied to both
  spondylocostal dysostosis (SCDO; asymmetric, chaotic vertebral and rib
  malsegmentation) and spondylothoracic dysostosis (STD; the symmetric,
  posteriorly fused "crab-like"/"fan-like" rib form, classically caused by MESP2
  and prevalent in Puerto Rican families). MONDO does not model STD as a distinct
  disease term: "Jarcho-Levin syndrome" is a RELATED synonym of this general SCDO
  term (MONDO:0000359, OMIMPS:277300), whereas "spondylothoracic dysostosis"
  appears only as a scattered synonym on gene-specific SCDO subtype terms
  (SCDO1/DLL3 MONDO:0020692, OMIM:277300; SCDO5/TBX6 MONDO:0007389, OMIM:122600)
  — neither of which is the MESP2 entity. The MESP2 form maps to spondylocostal
  dysostosis 2 (SCDO2; MONDO:0012097, OMIM:608681). Curators should therefore
  record Jarcho-Levin and STD as synonyms here rather than create a separate,
  ambiguously grounded entry (a known named-entity-confusion hazard verified
  2026-06-29). The `has_subtypes` list now pins each numbered SCDO type to its
  gene and MONDO term, so a curator or tool resolving "spondylothoracic
  dysostosis" can be routed to the SCDO2/MESP2 subtype rather than to the DLL3
  or TBX6 terms that carry the STD synonym upstream. The upstream MONDO
  synonym-scope cleanup is tracked in issue #4957.
disease_term:
  preferred_term: spondylocostal dysostosis
  term:
    id: MONDO:0000359
    label: spondylocostal dysostosis
parents:
- Vertebral Malformation Disorders
has_subtypes:
- name: SCDO1
  display_name: SCDO1 (DLL3-related)
  subtype_term:
    preferred_term: spondylocostal dysostosis 1, autosomal recessive
    term:
      id: MONDO:0020692
      label: spondylocostal dysostosis 1, autosomal recessive
  description: >-
    SCDO1 (OMIM:277300) is caused by biallelic pathogenic variants in DLL3,
    which encodes a Notch ligand acting in the presomitic-mesoderm segmentation
    clock. It was the first molecularly solved form of SCDO and produces a
    consistent, distinctive pattern of abnormal vertebral segmentation
    affecting the entire spine. Note that MONDO carries "spondylothoracic
    dysostosis" as a RELATED synonym on this DLL3 term; that synonym is a
    named-entity-confusion hazard, because the classic symmetric
    "crab-like-rib" STD entity is MESP2-related (see the SCDO2 subtype).
  genes:
  - preferred_term: DLL3
    term:
      id: hgnc:2909
      label: DLL3
  inheritance:
  - name: Autosomal Recessive
  evidence:
  - reference: PMID:10742114
    reference_title: "Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Here we have cloned and sequenced human DLL3 to evaluate it as a candidate gene for SD and identified mutations in three autosomal recessive SD families.
    explanation: >-
      Establishes biallelic DLL3 variants as a cause of autosomal recessive
      spondylocostal dysostosis, the lesion that defines the SCDO1 subtype.
  - reference: PMID:16385447
    reference_title: Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2)."
    explanation: >-
      Anchors the numbered subtype nomenclature, assigning DLL3 to SCDO1 and
      MESP2 to SCDO2.
- name: SCDO2
  display_name: SCDO2 (MESP2-related; includes spondylothoracic dysostosis / Puerto Rican Jarcho-Levin)
  subtype_term:
    preferred_term: spondylocostal dysostosis 2, autosomal recessive
    term:
      id: MONDO:0012097
      label: spondylocostal dysostosis 2, autosomal recessive
  description: >-
    SCDO2 (OMIM:608681) is caused by biallelic pathogenic variants in MESP2, a
    bHLH transcription factor that translates segmentation-clock oscillations
    into somite-boundary and rostrocaudal-polarity specification. This is the
    subtype that carries the spondylothoracic dysostosis (STD) / classic Puerto
    Rican "Jarcho-Levin syndrome" phenotype — symmetric, posteriorly fused
    "crab-like" ribs with a shortened trunk and early-childhood respiratory
    compromise — attributable to a MESP2 E103X founder mutation. Recording that
    identity here is the dismech-side mitigation for the ontology gap in
    issue #4957: MONDO has no distinct STD class, and the string
    "spondylothoracic dysostosis" appears as a synonym on the DLL3 (SCDO1) and
    TBX6 (SCDO5) terms rather than on this MESP2 term.
  genes:
  - preferred_term: MESP2
    term:
      id: hgnc:29659
      label: MESP2
  geography:
  - Puerto Rico
  inheritance:
  - name: Autosomal Recessive
  evidence:
  - reference: PMID:15122512
    reference_title: Mutated MESP2 causes spondylocostal dysostosis in humans.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Using a genomewide scanning strategy in one consanguineous family with two affected children, we demonstrated linkage to 15q21.3-15q26.1 and furthermore identified a 4-bp duplication mutation in the human MESP2 gene that codes for a basic helix-loop-helix transcription factor.
    explanation: >-
      Original identification of biallelic MESP2 variants as a cause of
      spondylocostal dysostosis, defining the SCDO2 subtype.
  - reference: PMID:18485326
    reference_title: Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is an autosomal-recessive disorder characterized by abnormal vertebral segmentation and defects affecting spine formation, with complete bilateral fusion of the ribs at the costovertebral junction producing a "crab-like" configuration of the thorax.
    explanation: >-
      Defines the symmetric "crab-like"-rib STD/Jarcho-Levin phenotype that this
      subtype carries, distinguishing it from the chaotic, asymmetric
      malsegmentation of the other SCDO subtypes.
  - reference: PMID:18485326
    reference_title: Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Our findings suggest a founder-effect mutation in the MESP2 gene as a major cause of the classical Puerto Rican form of STD/JLS.
    explanation: >-
      Grounds the STD/Jarcho-Levin eponym on MESP2 (i.e., SCDO2) rather than on
      the DLL3 or TBX6 terms that carry the STD synonym in MONDO, and supports
      the Puerto Rican geography annotation.
- name: SCDO3
  display_name: SCDO3 (LFNG-related)
  subtype_term:
    preferred_term: spondylocostal dysostosis 3, autosomal recessive
    term:
      id: MONDO:0012349
      label: spondylocostal dysostosis 3, autosomal recessive
  description: >-
    SCDO3 (OMIM:609813) is caused by biallelic pathogenic variants in LFNG
    (LUNATIC FRINGE), a glycosyltransferase that modifies Notch receptors and is
    required for correct oscillation of the segmentation clock. The reported
    vertebral phenotype is severe. GeneReviews notes that neurologic problems
    are a management consideration specifically in LFNG-related SCDO.
  genes:
  - preferred_term: LFNG
    term:
      id: hgnc:6560
      label: LFNG
  inheritance:
  - name: Autosomal Recessive
  evidence:
  - reference: PMID:16385447
    reference_title: Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD.
    explanation: >-
      Original identification of LFNG as the third autosomal recessive SCDO
      gene, defining the SCDO3 subtype.
  - reference: PMID:20301771
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Standard treatment of neurologic problems associated with LFNG-related SCDO.
    explanation: >-
      GeneReviews singles out LFNG-related SCDO as the form with neurologic
      problems requiring management.
- name: SCDO4
  display_name: SCDO4 (HES7-related)
  subtype_term:
    preferred_term: spondylocostal dysostosis 4, autosomal recessive
    term:
      id: MONDO:0013366
      label: spondylocostal dysostosis 4, autosomal recessive
  description: >-
    SCDO4 (OMIM:613686) is caused by biallelic pathogenic variants in HES7, the
    Notch-driven transcriptional repressor that generates the oscillation of the
    segmentation clock itself. HES7-related disease is distinguished from the
    other SCDO subtypes by co-occurring laterality defects (dextrocardia with
    situs inversus) and neural tube malformations, consistent with an additional
    role outside somitogenesis.
  genes:
  - preferred_term: HES7
    term:
      id: hgnc:15977
      label: HES7
  inheritance:
  - name: Autosomal Recessive
  evidence:
  - reference: PMID:23897666
    reference_title: Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: We found that both individuals were homozygous for the same mutation in HES7, and that this mutation caused a significant reduction of HES7 protein function; HES7 mutation causes SCD4.
    explanation: >-
      Explicitly assigns HES7 to the SCDO4 subtype and demonstrates loss of HES7
      function in affected individuals.
  - reference: PMID:23897666
    reference_title: Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: In conclusion, it appears that mutation of HES7 is uniquely associated with defects in vertebral, heart and neural tube formation, and this observation will help provide a discriminatory diagnostic guide in patients with SCD, as well as inform molecular genetic testing.
    explanation: >-
      Supports the laterality and neural tube findings as the features that
      differentiate SCDO4 from the other subtypes.
- name: SCDO5
  display_name: SCDO5 (TBX6-related)
  subtype_term:
    preferred_term: spondylocostal dysostosis 5
    term:
      id: MONDO:0007389
      label: spondylocostal dysostosis 5
  description: >-
    SCDO5 (OMIM:122600) is caused by pathogenic variants in TBX6, the
    T-box transcription factor that patterns the presomitic mesoderm at the
    determination wavefront. Unlike SCDO1-SCDO4, SCDO5 was first described with
    autosomal dominant transmission (a stoploss variant acting by
    haploinsufficiency), although GeneReviews also lists TBX6 among the genes in
    which biallelic variants confirm autosomal recessive SCDO. Compound TBX6
    null-plus-hypomorphic dosage insufficiency is modeled separately in the
    TBX6-Associated_Congenital_Scoliosis entry. MONDO carries
    "spondylothoracic dysostosis" as an EXACT synonym on this TBX6 term, which
    is the specific mis-resolution hazard described in issue #4957 — the STD
    entity is MESP2-related (SCDO2), not TBX6-related.
  genes:
  - preferred_term: TBX6
    term:
      id: hgnc:11605
      label: TBX6
  inheritance:
  - name: Autosomal Dominant
    description: >-
      The originally described SCDO5 family showed autosomal dominant
      transmission of a TBX6 stoploss variant acting by haploinsufficiency.
      GeneReviews treats this as the exception rather than the rule, noting it
      was reported in a single three-generation family.
    evidence:
    - reference: PMID:23335591
      reference_title: Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.
      explanation: >-
        Original report establishing autosomal dominant transmission for
        TBX6-related SCDO.
  - name: Autosomal Recessive
    description: >-
      TBX6 is also listed among the genes in which biallelic pathogenic variants
      cause autosomal recessive SCDO, so SCDO5 is not exclusively dominant. This
      block records the recessive mode alongside the dominant one rather than
      leaving it in the subtype description, where it is not queryable.
    evidence:
    - reference: PMID:20301771
      reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: SCDO caused by biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 is inherited in an autosomal recessive manner.
      explanation: >-
        GeneReviews names TBX6 among the genes whose biallelic variants produce
        autosomal recessive SCDO, which is the basis for recording a recessive
        mode on the TBX6-anchored SCDO5 subtype.
  evidence:
  - reference: PMID:23335591
    reference_title: Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Here, we have used exome capture and next-generation sequencing to identify a stoploss mutation in TBX6 that segregates with disease in two generations of one family.
    explanation: >-
      Original identification of TBX6 as an SCDO gene, defining the SCDO5
      subtype.
  - reference: PMID:23335591
    reference_title: Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.
    explanation: >-
      Supports the autosomal dominant inheritance that distinguishes SCDO5 from
      the recessive SCDO1-SCDO4 subtypes.
- name: SCDO6
  display_name: SCDO6 (RIPPLY2-related)
  subtype_term:
    preferred_term: spondylocostal dysostosis 6, autosomal recessive
    term:
      id: MONDO:0014694
      label: spondylocostal dysostosis 6, autosomal recessive
  description: >-
    SCDO6 (OMIM:616566) is caused by biallelic pathogenic variants in RIPPLY2,
    which acts with MESP2 to establish somite rostrocaudal polarity. Reported
    individuals have cervical- and thoracic-predominant vertebral body
    malformations with limited rib involvement, and myelopathy from congenital
    cervical spine malformation is a recognized complication.
  genes:
  - preferred_term: RIPPLY2
    term:
      id: hgnc:21390
      label: RIPPLY2
  inheritance:
  - name: Autosomal Recessive
  evidence:
  - reference: PMID:25343988
    reference_title: Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition.
    explanation: >-
      Report that first associated compound heterozygous RIPPLY2 variants with
      segmentation defects of the vertebrae, the basis of the SCDO6 subtype.
      This is the paper's own concluding sentence, which names RIPPLY2
      explicitly; it replaces a generic SDV-background sentence that never
      mentioned the gene and so could not license the association claim.
  - reference: PMID:33410135
    reference_title: Congenital cervical spine malformation due to bi-allelic RIPPLY2 variants in spondylocostal dysostosis type 6.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: All patients had multiple vertebral body malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae.
    explanation: >-
      Confirms biallelic RIPPLY2 variants as the SCDO6 lesion and describes the
      cervical-predominant vertebral phenotype with myelopathy.
inheritance:
- name: Autosomal Recessive
  description: >-
    SCDO is most commonly inherited in an autosomal recessive manner, caused by
    biallelic pathogenic variants in segmentation-clock / Notch-pathway genes.
  evidence:
  - reference: PMID:20301771
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Identification of biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 can confirm the diagnosis of autosomal recessive SCDO.
    explanation: >-
      GeneReviews establishes autosomal recessive inheritance and the
      causative Notch-pathway gene panel for SCDO.
classifications:
  isds_skeletal_category:
  - classification_value: dysostoses_with_predominant_vertebral_and_costal_involvement
    notes: >-
      ISDS Nosology and Classification of Genetic Skeletal Disorders, 2019
      revision (Mortier et al., PMID:31633310), Table 1 group 35 "Dysostoses with
      predominant vertebral with and without costal involvement"; listed as
      "Spondylocostal dysostosis".
prevalence:
- population: General
  prevalence_class: UNKNOWN
  percentage: Unknown
  notes: >-
    SCDO is a rare disorder documented mainly through case reports, small
    cohorts, and molecularly characterized families rather than formal
    population-prevalence studies; autosomal recessive forms are more frequent in
    consanguineous populations.
pathophysiology:
- name: Segmentation Clock Gene Disruption
  conforms_to: "axial_segmentation_serial_homology#Segmentation Clock and Wavefront Dysfunction"
  description: >-
    Biallelic loss-of-function variants in Notch-pathway and segmentation-clock
    genes (DLL3, MESP2, LFNG, HES7, TBX6; also RIPPLY2) disrupt the oscillatory
    Notch signaling that drives the segmentation clock in the presomitic
    mesoderm. Proper regulation of Notch signaling is an absolute requirement for
    correct patterning of the axial skeleton.
  role: trigger
  genes:
  - preferred_term: DLL3
    term:
      id: hgnc:2909
      label: DLL3
  - preferred_term: MESP2
    term:
      id: hgnc:29659
      label: MESP2
  - preferred_term: LFNG
    term:
      id: hgnc:6560
      label: LFNG
  - preferred_term: HES7
    term:
      id: hgnc:15977
      label: HES7
  - preferred_term: TBX6
    term:
      id: hgnc:11605
      label: TBX6
  - preferred_term: RIPPLY2
    term:
      id: hgnc:21390
      label: RIPPLY2
  cell_types:
  - preferred_term: Presomitic (Paraxial) Mesoderm Cell
    term:
      id: CL:0011007
      label: paraxial cell
  biological_processes:
  - preferred_term: Somitogenesis
    term:
      id: GO:0001756
      label: somitogenesis
    modifier: ABNORMAL
  - preferred_term: Notch Signaling Pathway
    term:
      id: GO:0007219
      label: Notch signaling pathway
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16385447
    reference_title: Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease.
    explanation: >-
      Identifies the SCDO genes (DLL3, MESP2, LFNG) as Notch-pathway components,
      the molecular trigger of the disorder.
  - reference: PMID:20301771
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Identification of biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 can confirm the diagnosis of autosomal recessive SCDO.
    explanation: >-
      Enumerates the segmentation-clock / Notch-pathway genes whose biallelic
      variants cause SCDO.
  downstream:
  - target: Disrupted Somite Formation
    description: Loss of Notch-driven clock oscillation corrupts periodic somite formation.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - loss of cyclic Notch target-gene oscillation in the presomitic mesoderm
- name: Disrupted Somite Formation
  conforms_to: "axial_segmentation_serial_homology#Disrupted Somite Boundary Formation"
  description: >-
    Loss of clock oscillation and wavefront positioning corrupts the periodic
    formation of somite boundaries, so somites form with abnormal timing, number,
    or rostrocaudal polarity. The metameric template from which the vertebrae and
    ribs derive is therefore mis-specified.
  role: central_effector
  cell_types:
  - preferred_term: Presomitic (Paraxial) Mesoderm Cell
    term:
      id: CL:0011007
      label: paraxial cell
  biological_processes:
  - preferred_term: Segmentation
    term:
      id: GO:0035282
      label: segmentation
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16385447
    reference_title: Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis.
    explanation: >-
      States that SCDO arises from disrupted somitogenesis, the central effector
      step.
  - reference: PMID:17965051
    reference_title: FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: The FGF pathway establishes a posterior-to-anterior signaling gradient in the presomitic mesoderm (PSM), which controls cell maturation and is involved in the positioning of segmental boundaries.
    explanation: >-
      Describes the PSM wavefront that positions segmental boundaries, the
      mechanism whose disruption mis-forms somites. Evidence source is
      MODEL_ORGANISM (mouse).
  downstream:
  - target: Vertebral and Rib Malsegmentation
    description: Mis-specified somites give rise to malsegmented vertebrae and ribs.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - mis-specified metameric somite template
- name: Vertebral and Rib Malsegmentation
  conforms_to: "axial_segmentation_serial_homology#Vertebral and Costal Malsegmentation"
  description: >-
    Because the vertebrae and ribs are serially homologous somite derivatives,
    the mis-segmentation manifests as a coordinated multi-segment malformation
    bundle: multiple vertebral segmentation defects (hemivertebrae, fused/block
    vertebrae) together with rib abnormalities, producing a short trunk and, in
    severe disease, a small thorax with respiratory compromise.
  role: consequence
  cell_types:
  - preferred_term: Chondrocyte
    term:
      id: CL:0000138
      label: chondrocyte
  - preferred_term: Osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  biological_processes:
  - preferred_term: Embryonic Skeletal System Morphogenesis
    term:
      id: GO:0048704
      label: embryonic skeletal system morphogenesis
    modifier: ABNORMAL
  evidence:
  - reference: PMID:20301771
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs
    explanation: >-
      Defines the serially homologous axial bundle — multiple vertebral
      segmentation defects together with rib abnormalities.
  - reference: PMID:29765785
    reference_title: "Spondylocostal Dysostosis: A Literature Review and Case Report with Long-Term Follow-Up of a Conservatively Managed Patient."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Patients with spondylocostal dysostosis (SCD) have congenital spine and rib deformities associated with frequently severe thoracic insufficiency and respiratory compromise.
    explanation: >-
      Documents combined congenital spine and rib deformities with thoracic
      insufficiency, the clinical consequence.
phenotypes:
- name: Multiple Vertebral Segmentation Defects
  description: >-
    Multiple hemivertebrae and fused/block vertebrae are the defining
    radiographic feature of SCDO, reflecting mis-segmentation across many axial
    segments.
  phenotype_term:
    preferred_term: Hemivertebrae
    term:
      id: HP:0002937
      label: Hemivertebrae
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs
    explanation: SCDO is defined by multiple vertebral segmentation defects.
- name: Vertebral Fusion
  description: Fused/block vertebrae are part of the multiple-segmentation-defect phenotype.
  phenotype_term:
    preferred_term: Vertebral fusion
    term:
      id: HP:0002948
      label: Vertebral fusion
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs
    explanation: Vertebral fusion is among the multiple vertebral segmentation defects of SCDO.
- name: Rib Abnormalities
  description: >-
    Rib malalignment, fusion, or abnormal number accompanies the vertebral
    defects, reflecting the shared somite origin of vertebrae and ribs.
  phenotype_term:
    preferred_term: Abnormal rib morphology
    term:
      id: HP:0000772
      label: Abnormal rib morphology
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs
    explanation: Rib abnormalities are a defining component of SCDO.
- name: Disproportionate Short-Trunk Short Stature
  description: The axial malsegmentation produces a short trunk in proportion to height.
  phenotype_term:
    preferred_term: Disproportionate short-trunk short stature
    term:
      id: HP:0003521
      label: Disproportionate short-trunk short stature
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: a short trunk in proportion to height
    explanation: SCDO is characterized by a short trunk in proportion to height.
- name: Short Neck
  description: A short neck results from cervical vertebral segmentation defects.
  phenotype_term:
    preferred_term: Short neck
    term:
      id: HP:0000470
      label: Short neck
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: short neck
    explanation: Short neck is a characteristic clinical feature of SCDO.
- name: Scoliosis
  description: Most affected individuals have non-progressive mild scoliosis.
  phenotype_term:
    preferred_term: Scoliosis
    term:
      id: HP:0002650
      label: Scoliosis
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: non-progressive mild scoliosis in most affected individuals
    explanation: Mild non-progressive scoliosis occurs in most individuals with SCDO.
- name: Respiratory Insufficiency
  description: >-
    Neonates with severe disease can have respiratory compromise from a small
    thorax; lung growth may improve after infancy.
  phenotype_term:
    preferred_term: Respiratory insufficiency
    term:
      id: HP:0002093
      label: Respiratory insufficiency
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: Respiratory function in neonates with severe disease may be compromised by reduced size of the thorax.
    explanation: A small thorax can compromise neonatal respiratory function in severe SCDO.
- name: Inguinal Hernia
  description: >-
    Males with SCDO are at increased risk for inguinal hernia, a sex-specific,
    management-relevant feature for which GeneReviews advises surveillance of
    affected young males.
  phenotype_term:
    preferred_term: Inguinal hernia
    term:
      id: HP:0000023
      label: Inguinal hernia
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: Males with SCDO appear to be at increased risk for inguinal hernia.
    explanation: GeneReviews documents an increased risk of inguinal hernia in males with SCDO.
- name: Pulmonary Hypertension
  description: >-
    In severely affected individuals with restricted pulmonary capacity, chronic
    respiratory compromise can lead to pulmonary hypertension that may eventually
    impact cardiac function.
  phenotype_term:
    preferred_term: Pulmonary hypertension
    term:
      id: HP:0002092
      label: Pulmonary arterial hypertension
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: there is a possibility that pulmonary hypertension may eventually impact cardiac function
    explanation: GeneReviews notes that restricted pulmonary capacity in severe SCDO can lead to pulmonary hypertension affecting cardiac function.
treatments:
- name: Scoliosis Surgical Management
  description: >-
    Surgical intervention for significant scoliosis, including external bracing
    and growth-friendly instrumentation such as a vertical expandable prosthetic
    titanium rib (VEPTR) to expand thoracic volume.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: orthopedic surgical procedure
    term:
      id: NCIT:C16186
      label: Orthopedic Surgical Procedure
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: Surgical intervention may be necessary when scoliosis is significant
    explanation: Significant scoliosis in SCDO may require surgical management.
- name: Respiratory Support
  description: >-
    Respiratory support, including intensive care, for the minority of
    individuals with acute respiratory distress or chronic respiratory failure.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:20301771
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    reference_title: "Spondylocostal Dysostosis, Autosomal Recessive."
    snippet: Respiratory support, including intensive care, is provided as needed
    explanation: Respiratory support is provided for severe SCDO with respiratory compromise.
references:
- reference: PMID:20301771
  title: "Spondylocostal Dysostosis, Autosomal Recessive."
  tags:
  - GeneReviews
  findings: []
📚

References & Deep Research

References

1
PMID:20301771
Spondylocostal Dysostosis, Autosomal Recessive.
No top-level findings curated for this source.