Details of Disease

General Information of Disease (ID: DIS7V9PS)

• Disease Name: Freeman-Sheldon syndrome
• Synonyms: FSS; arthrogryposis distal type 2A; arthrogryposis, distal, type 2A; DA2A; craniocarpotarsal dysplasia; Craniocarpotarsal dysplasia; Craniocarpotarsal dystrophy; craniocarpotarsal dystrophy; windmill-vane-hand syndrome; whistling face-windmill vane hand syndrome; Freeman Sheldon Syndrome; distal arthrogryposis type 2A; Freeman Sheldon syndrome; arthrogryposis, distal, type 2A (Freeman-Sheldon); whistling-face syndrome; cranio-carpo-tarsal syndrome; Freeman-Sheldon syndrome; whistling face syndrome
• Definition: A very rare, multiple congenital contractures syndrome characterized by a microstomia with a whistling appearance of the mouth, distinctive facies, club foot and joint contractures. FSS is the most severe form of distal arthrogryposis.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DIS2BIP8: Congenital nervous system disorder
  DIS3QIEL: Distal arthrogryposis
  DISC81CM: Arthrogryposis
  DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability
  DIS7V9PS: Freeman-Sheldon syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0008675
  MESH ID: C535483
  UMLS CUI: C0265224
  OMIM ID: 193700
  MedGen ID: 120516
  Orphanet ID: 2053
  SNOMED CT ID: 52616002

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
DHODH	TTLVP78	Strong	Biomarker	[1]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TNNI2	OTGGZFSC	Limited	Biomarker	[2]
TNNT3	OT4C498E	Limited	Biomarker	[3]
NALCN	OTWY7DS0	Supportive	Autosomal dominant	[4]
RAB18	OTNMAQLS	moderate	Biomarker	[5]
CNTN3	OTC1274J	Strong	Biomarker	[6]
MOCOS	OT0TL3Q5	Strong	Biomarker	[6]
MYBPC1	OTRPN93S	Strong	Genetic Variation	[3]
SMCP	OTXKY794	Strong	Biomarker	[6]
TBC1D20	OTDL1T6E	Strong	Biomarker	[7]
TPM2	OTA1L0P8	Strong	Biomarker	[3]
FBN2	OT3KYJQL	Definitive	Biomarker	[8]
MYH3	OTOCCGEB	Definitive	Autosomal dominant	[9]

References

• [1] Identifying Mendelian disease genes with the variant effect scoring tool.BMC Genomics. 2013;14 Suppl 3(Suppl 3):S3. doi: 10.1186/1471-2164-14-S3-S3. Epub 2013 May 28.
• [2] 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.
• [3] A novel TNNI2 mutation causes Freeman-Sheldon syndrome in a Chinese family with an affected adult with only facial contractures.Gene. 2013 Sep 25;527(2):630-5. doi: 10.1016/j.gene.2013.06.082. Epub 2013 Jul 11.
• [4] De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay. Am J Hum Genet. 2015 Mar 5;96(3):462-73. doi: 10.1016/j.ajhg.2015.01.003. Epub 2015 Feb 12.
• [5] ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon degeneration caused by a deletion in Rab18.Exp Neurol. 2015 May;267:143-51. doi: 10.1016/j.expneurol.2015.03.003. Epub 2015 Mar 13.
• [6] Home-Based Exercise Enhances Health-Related Quality of Life in Persons With Spinal Cord Injury: ARandomized Controlled Trial.Arch Phys Med Rehabil. 2018 Oct;99(10):1998-2006.e1. doi: 10.1016/j.apmr.2018.05.008. Epub 2018 Jun 11.
• [7] Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet. 2013 Dec 5;93(6):1001-14. doi: 10.1016/j.ajhg.2013.10.011. Epub 2013 Nov 14.
• [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] Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally. Arch Neurol. 2008 Aug;65(8):1083-90. doi: 10.1001/archneur.65.8.1083.