Details of Disease

General Information of Disease (ID: DISQY7K4)

• Disease Name: Orofaciodigital syndrome type 6
• Synonyms: oral-Facial-digital syndrome, type 6; polydactyly - cleft lip/palate - psychomotor retardation; Ofds 6; Vradi-Papp syndrome; Vradi syndrome; polydactyly cleft lip palate psychomotor retardation; orofaciodigital syndrome 6; polydactyly, cleft Lip/palate or lingual lump, and psychomotor retardation; oral-facial-digital syndrome type 6; polydactyly-cleft lip/palate-psychomotor retardation syndrome; Varadi-Papp syndrome; Joubert syndrome with oral-facial-digital syndrome; Joubert syndrome with orofaciodigital defect; orofaciodigital syndrome VI; OFD6; Varadi syndrome; orofaciodigital syndrome type 6
• Definition: Joubert syndrome with orofaciodigital defect (or oral-facial-digital syndrome type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD) characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly.
• Disease Hierarchy:
  DISSB296: Orofaciodigital syndrome
  DISD715V: Hereditary neurological disease
  DISOV08L: Central nervous system malformation
  DIS9LHZ1: Joubert syndrome 17
  DISQY7K4: Orofaciodigital syndrome type 6
• Disease Identifiers:
  MONDO ID: MONDO_0010176
  MESH ID: C536531
  UMLS CUI: C2745997
  OMIM ID: 277170
  MedGen ID: 411200
  Orphanet ID: 2754
  SNOMED CT ID: 721873007

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
CEP290	TT3XBOV	Strong	Genetic Variation	[1]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FAM149B1	OTUBPEJ6	Supportive	Autosomal recessive	[2]
KIAA0753	OTMFT2I9	Supportive	Autosomal recessive	[3]
KIF7	OT1J6NAW	Supportive	Autosomal recessive	[4]
OFD1	OTAZW5TK	Supportive	Autosomal recessive	[4]
PDE6D	OTIFVXWD	Supportive	Autosomal recessive	[5]
TCTN3	OTZSHERV	Supportive	Autosomal recessive	[6]
TMEM216	OT1LOKOI	Supportive	Autosomal recessive	[7]
INTU	OTXB13E6	Strong	Biomarker	[8]
TCTN1	OTG5KEV8	Strong	Genetic Variation	[9]
TMEM231	OTF4UYIE	Strong	Genetic Variation	[1]
CPLANE1	OTXGGNNB	Definitive	Mitochondrial	[10]

References

• [1] MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.PLoS Biol. 2016 Mar 16;14(3):e1002416. doi: 10.1371/journal.pbio.1002416. eCollection 2016 Mar.
• [2] Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans. Am J Hum Genet. 2019 Apr 4;104(4):731-737. doi: 10.1016/j.ajhg.2019.02.018. Epub 2019 Mar 21.
• [3] OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome. Hum Mol Genet. 2016 Feb 1;25(3):497-513. doi: 10.1093/hmg/ddv488. Epub 2015 Dec 7.
• [4] Joubert Syndrome. 2003 Jul 9 [updated 2017 Jun 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [5] A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. Hum Mutat. 2014 Jan;35(1):137-46. doi: 10.1002/humu.22470.
• [6] TCTN3 mutations cause Mohr-Majewski syndrome. Am J Hum Genet. 2012 Aug 10;91(2):372-8. doi: 10.1016/j.ajhg.2012.06.017.
• [7] Joubert Syndrome and related disorders. Orphanet J Rare Dis. 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20.
• [8] INTU-related oral-facial-digital syndrome type VI: A confirmatory report.Clin Genet. 2018 Jun;93(6):1205-1209. doi: 10.1111/cge.13238. Epub 2018 Apr 6.
• [9] Expanding the allelic disorders linked to TCTN1 to include Varadi syndrome (Orofaciodigital syndrome type VI). Am J Med Genet A. 2017 Sep;173(9):2439-2441. doi: 10.1002/ajmg.a.38336. Epub 2017 Jun 20.
• [10] C5orf42 is the major gene responsible for OFD syndrome type VI. Hum Genet. 2014 Mar;133(3):367-77. doi: 10.1007/s00439-013-1385-1. Epub 2013 Nov 1.