Details of Disease

General Information of Disease (ID: DIS668BA)

• Disease Name: Lethal multiple pterygium syndrome
• Synonyms: pterygium syndrome multiple lethal type; pterygium syndrome, multiple, lethal type; multiple pterygium syndrome, lethal type; multiple pterygium syndrome lethal type; lethal multiple pterygium syndrome; autosomal recessive lethal multiple pterygium syndrome; LMPS
• Definition: Multiple pterygium syndrome lethal type is a very rare genetic condition affecting the skin, muscles and skeleton. It is characterized by minor facial abnormalities, prenatal growth deficiency, spine defects, joint contractures, and webbing (pterygia)of the neck, elbows, back of the knees, armpits, and fingers. Fetuses with this condition are usually not born. Some of the prenatal complications include cystic hygroma, hydrops, diaphragmatic hernia, polyhydramnios, underdevelopment of the heart and lungs, microcephaly, bone fusions, joint dislocations, spinal fusion, andbone fractures. Both X-linked and autosomal recessive inheritance have been proposed. Mutations in the CHRNG, CHRNA1, and CHRND genes have been found to cause this condition.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISK8Z6W: Multiple pterygium syndrome
  DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
  DIS668BA: Lethal multiple pterygium syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0009668
  MESH ID: C537377
  UMLS CUI: C1854678
  OMIM ID: 253290
  MedGen ID: 381473
  Orphanet ID: 33108
  SNOMED CT ID: 60192008

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
RYR1	TTU5CIX	Supportive	Autosomal recessive	[1]
CHRNA1	TT54JVQ	moderate	Biomarker	[2]
CHRNA1	TT54JVQ	Strong	Autosomal recessive	[3]
RYR1	TTU5CIX	Strong	GermlineCausalMutation	[1]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GBE1	OTK2N05B	Limited	Genetic Variation	[4]
TPM2	OTA1L0P8	Limited	Genetic Variation	[5]
NEB	OT7P9IR3	Supportive	Autosomal recessive	[6]
RYR1	OTWUB65S	Supportive	Autosomal recessive	[1]
CHRNA1	OT2Z2TCB	Strong	Autosomal recessive	[3]
CHRND	OTLUUP7C	Strong	Autosomal recessive	[7]
CHRNG	OTXC2UR7	Strong	Autosomal recessive	[8]

References

• [1] Lethal multiple pterygium syndrome, the extreme end of the RYR1 spectrum. BMC Musculoskelet Disord. 2016 Mar 1;17:109. doi: 10.1186/s12891-016-0947-5.
• [2] Clinical Reasoning: A child with arthrogryposis: Congenital myasthenic syndrome-CHRNA1 mutation.Neurology. 2018 Sep 4;91(10):e995-e998. doi: 10.1212/WNL.0000000000006126.
• [3] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [4] Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations.Neuromuscul Disord. 2013 Feb;23(2):165-9. doi: 10.1016/j.nmd.2012.11.005. Epub 2012 Dec 3.
• [5] Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy.Neuromuscul Disord. 2009 Feb;19(2):118-23. doi: 10.1016/j.nmd.2008.11.009. Epub 2009 Jan 19.
• [6] Lethal multiple pterygium syndrome: A severe phenotype associated with a novel mutation in the nebulin gene. Neuromuscul Disord. 2017 Jun;27(6):537-541. doi: 10.1016/j.nmd.2017.01.013. Epub 2017 Jan 18.
• [7] Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. J Clin Invest. 2001 Jul;108(1):125-30. doi: 10.1172/JCI12935.
• [8] Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am J Hum Genet. 2006 Aug;79(2):303-12. doi: 10.1086/506257. Epub 2006 Jun 20.