Details of Disease

General Information of Disease (ID: DISVMP0Y)

• Disease Name: Gordon syndrome
• Synonyms: arthrogryposis distal type 3; DA3; arthrogryposis, distal, type 3; arthrogryposis multiplex congenita, distal, type 2A; camptodactyly, cleft palate, and clubfoot; distal arthrogryposis type 3; camptodactyly-cleft palate-clubfoot syndrome; distal arthrogryposis type IIA; Gordon syndrome
• Definition: An extremely rare multiple congenital malformation syndrome characterized by congenital contractures of hand and feet with variable degrees of severity of camptodactyly, clubfoot and, less frequently, cleft palate. Intelligence is normal but in some cases, additional abnormalities, such as short stature, kyphoscoliosis, ptosis, micrognathia, and cryptorchidism may also be present. Gordon syndrome, Marden-Walker syndrome and arthrogryposis with oculomotor limitation and electroretinal anomalies clinically and genetically overlap, and could represent variable expressions of the same condition.
• Disease Hierarchy:
  DIS3QIEL: Distal arthrogryposis
  DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability
  DISVMP0Y: Gordon syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0007252
  MESH ID: C537288
  UMLS CUI: C0220666
  OMIM ID: 114300
  MedGen ID: 66314
  Orphanet ID: 376
  SNOMED CT ID: 897570002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KCNJ1	TTJ13ST	moderate	Altered Expression	[1]
CUL3	TTPCU0Q	Strong	Biomarker	[2]
SLC12A3	TTP362L	Strong	Genetic Variation	[3]
WNK1	TTJ9UMX	Strong	Genetic Variation	[1]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KLHL3	OTEJ6850	Disputed	Genetic Variation	[4]
CLDN8	OT7IIWXG	moderate	Biomarker	[5]
OSR1	OTB19LEQ	moderate	Biomarker	[6]
TNNI2	OTGGZFSC	moderate	Biomarker	[7]
FBN2	OT3KYJQL	Definitive	Biomarker	[8]
PIEZO2	OTQ7AT38	Definitive	Autosomal dominant	[9]

References

• [1] Gordon Syndrome: a continuing story.Pediatr Nephrol. 2015 Nov;30(11):1903-8. doi: 10.1007/s00467-014-2956-7. Epub 2014 Dec 11.
• [2] Molecular insights from dysregulation of the thiazide-sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide-induced hyponatraemia.Clin Exp Pharmacol Physiol. 2013 Dec;40(12):876-84. doi: 10.1111/1440-1681.12115.
• [3] Detection of mutations in KLHL3 and CUL3 in families with FHHt (familial hyperkalaemic hypertension or Gordon's syndrome).Clin Sci (Lond). 2014 May;126(10):721-6. doi: 10.1042/CS20130326.
• [4] Three cases of Gordon syndrome with dominant KLHL3 mutations.J Pediatr Endocrinol Metab. 2017 Mar 1;30(3):361-364. doi: 10.1515/jpem-2016-0309.
• [5] Paracellular transport in the collecting duct.Curr Opin Nephrol Hypertens. 2016 Sep;25(5):424-8. doi: 10.1097/MNH.0000000000000253.
• [6] Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1.Biochem J. 2006 Jul 1;397(1):223-31. doi: 10.1042/BJ20060220.
• [7] A gain-of-function mutation in Tnni2 impeded bone development through increasing Hif3a expression in DA2B mice.PLoS Genet. 2014 Oct 23;10(10):e1004589. doi: 10.1371/journal.pgen.1004589. eCollection 2014 Oct.
• [8] ENU mutagenesis reveals a novel phenotype of reduced limb strength in mice lacking fibrillin 2.PLoS One. 2010 Feb 9;5(2):e9137. doi: 10.1371/journal.pone.0009137.
• [9] Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am J Hum Genet. 2014 May 1;94(5):734-44. doi: 10.1016/j.ajhg.2014.03.015. Epub 2014 Apr 10.