Details of Disease

General Information of Disease (ID: DISTPWFK)

• Disease Name: Spondylocostal dysostosis
• Synonyms: SCDO; SCD; Jarcho-Levin syndrome; spondylocostal dysplasia; spondylocostal dysostosis; costovertebral dysplasia; Spondylocostal Dysplasia
• Definition: Spondylocostal dysplasia is a rare genetic disorder characterized by defects of the bones of the spine (vertebrae) and abnormalities of the ribs. Ribs can be fused or missing in chaotic patterns. These malformations are present at birth (congenital).|Most times, spondylocostal dysplasia is inherited in an autosomal recessive manner and is caused by a change (mutation) in one of four genes, DLL3, MESP2, LFNG, HES7. Rarely, spondylocostal dysplasia can be inherited in an autosomal dominant manner. One gene, TBX6, is known to cause autosomal dominant spondylocostal dysplasia. There is significant confusion in the medical literature regarding names for spondylocostal dysplasia. For years, this disorder and a similar disorder, spondylothoracic dysplasia, were considered the same disorder and referred to as Jarcho-Levin syndrome. Researchers now know that these disorders are separate entities with different causes and associated malformations.
• Disease Hierarchy:
  DISQRITY: Spinal disease
  DISYKSRF: Genetic disease
  DISHPNVX: Dysplasia
  DISTPWFK: Spondylocostal dysostosis
• Disease Identifiers:
  MONDO ID: MONDO_0000359
  MESH ID: C537565
  UMLS CUI: C0265343
  OMIM ID: 277300
  MedGen ID: 82707
  SNOMED CT ID: 61367005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DLL3	TT1C9K6	Disputed	Biomarker	[1]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC35A3	DTB930Q	moderate	Biomarker	[2]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DMRT2	OTA39QNR	Limited	Autosomal recessive	[3]
HES7	OT6F9R7P	Limited	Genetic Variation	[4]
LFNG	OTPSUBN2	Limited	Genetic Variation	[1]
MESP2	OT7H4LYA	Limited	Genetic Variation	[5]
PAX1	OT0Y3MIM	moderate	Altered Expression	[6]
GDF6	OTERXWJU	Strong	Genetic Variation	[7]
PAX9	OT25J0F7	Strong	Altered Expression	[6]
RIPPLY2	OTDEEDLH	Strong	Biomarker	[8]
TBX6	OTW1Q8RM	Strong	Genetic Variation	[9]

References

• [1] Identification of novel LFNG mutations in spondylocostal dysostosis.J Hum Genet. 2019 Mar;64(3):261-264. doi: 10.1038/s10038-018-0548-2. Epub 2018 Dec 10.
• [2] A human case of SLC35A3-related skeletal dysplasia.Am J Med Genet A. 2017 Oct;173(10):2758-2762. doi: 10.1002/ajmg.a.38374. Epub 2017 Aug 4.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] An InVitro Human Segmentation Clock Model Derived from Embryonic Stem Cells.Cell Rep. 2019 Aug 27;28(9):2247-2255.e5. doi: 10.1016/j.celrep.2019.07.090.
• [5] Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun;82(6):1334-41. doi: 10.1016/j.ajhg.2008.04.014. Epub 2008 May 15.
• [6] Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review.Am J Med Genet A. 2003 Jul 15;120A(2):241-6. doi: 10.1002/ajmg.a.20192.
• [7] Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet. 2009 Mar 15;18(6):1110-21. doi: 10.1093/hmg/ddp008. Epub 2009 Jan 6.
• [8] A Cryptic Cause of Cardiac Arrest.J Emerg Med. 2019 Jan;56(1):e1-e4. doi: 10.1016/j.jemermed.2018.09.044. Epub 2018 Nov 9.
• [9] Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis.Clin Genet. 2017 Jun;91(6):908-912. doi: 10.1111/cge.12918. Epub 2017 Feb 22.