Details of Disease

General Information of Disease (ID: DISKDI9L)

• Disease Name: Fetal akinesia deformation sequence 1
• Synonyms: FADS1; Pena-Shokeir syndrome, type 1; Pena-Shokeir syndrome type 1
• Definition: Any fetal akinesia deformation sequence in which the cause of the disease is a mutation in the MUSK gene.
• Disease Hierarchy:
  DISAOT9S: Fetal akinesia deformation sequence
  DISKDI9L: Fetal akinesia deformation sequence 1
• Disease Identifiers:
  MONDO ID: MONDO_0100101
  MESH ID: C536647
  UMLS CUI: C1276035
  OMIM ID: 208150
  MedGen ID: 220903
  HPO ID: HP:0001989
  Orphanet ID: 994
  SNOMED CT ID: 401138005

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	Limited	Biomarker	[1]
MUSK	TT6SA0X	Strong	Autosomal recessive	[2]
MUSK	TT6SA0X	Strong	Genetic Variation	[3]
SLC18A3	TTV8KWS	Strong	GermlineCausalMutation	[4]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC18A3	DT3T2K0	Supportive	Autosomal recessive	[4]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NMNAT2	DE2HB58	Strong	Genetic Variation	[5]

This Disease Is Related to 21 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GLE1	OT0K44H1	Limited	Biomarker	[1]
DOK7	OTR2V7HO	Supportive	Autosomal recessive	[6]
MYOD1	OTV2S79X	Supportive	Autosomal recessive	[7]
NUP88	OT647WOR	Supportive	Autosomal recessive	[8]
SLC18A3	OTAUUY4B	Supportive	Autosomal recessive	[4]
CHRND	OTLUUP7C	moderate	Biomarker	[6]
CHRNG	OTXC2UR7	moderate	Genetic Variation	[9]
DPAGT1	OTYEJAGZ	moderate	Biomarker	[10]
PDHA1	OTGEU8IK	moderate	Genetic Variation	[11]
AGRN	OTWJENAZ	Strong	Biomarker	[12]
ASCC1	OTH4VAP9	Strong	Biomarker	[13]
DTNA	OTVBIRH2	Strong	Biomarker	[14]
FLAD1	OTY8R02L	Strong	Genetic Variation	[15]
GBE1	OTK2N05B	Strong	Biomarker	[16]
KIF14	OTXHT4JM	Strong	Biomarker	[1]
MUSK	OTERKP1U	Strong	Autosomal recessive	[2]
NEB	OT7P9IR3	Strong	Biomarker	[17]
OFD1	OTAZW5TK	Strong	Biomarker	[18]
PIGS	OTCC4CEN	Strong	Genetic Variation	[19]
KLHL40	OTMPMD6W	Definitive	Genetic Variation	[20]
RAPSN	OTGMSWDQ	Definitive	Autosomal recessive	[21]

References

• [1] Next generation sequencing in recurrent pregnancy loss-approaches and outcomes.Eur J Med Genet. 2020 Feb;63(2):103644. doi: 10.1016/j.ejmg.2019.04.001. Epub 2019 Apr 13.
• [2] Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence. Eur J Hum Genet. 2015 Sep;23(9):1151-7. doi: 10.1038/ejhg.2014.273. Epub 2014 Dec 24.
• [3] Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.Am J Med Genet A. 2019 Apr;179(4):655-658. doi: 10.1002/ajmg.a.61060. Epub 2019 Feb 4.
• [4] SLC18A3 variants lead to fetal akinesia deformation sequence early in pregnancy. Am J Med Genet A. 2019 Jul;179(7):1362-1365. doi: 10.1002/ajmg.a.61186. Epub 2019 May 6.
• [5] Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence.Exp Neurol. 2019 Oct;320:112961. doi: 10.1016/j.expneurol.2019.112961. Epub 2019 May 25.
• [6] Germline mutation in DOK7 associated with fetal akinesia deformation sequence. J Med Genet. 2009 May;46(5):338-40. doi: 10.1136/jmg.2008.065425. Epub 2009 Mar 3.
• [7] Deficiency of the myogenic factor MyoD causes a perinatally lethal fetal akinesia. J Med Genet. 2016 Apr;53(4):264-9. doi: 10.1136/jmedgenet-2015-103620. Epub 2016 Jan 5.
• [8] Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence. PLoS Genet. 2018 Dec 13;14(12):e1007845. doi: 10.1371/journal.pgen.1007845. eCollection 2018 Dec.
• [9] CHRNG genotype-phenotype correlations in the multiple pterygium syndromes. J Med Genet. 2012 Jan;49(1):21-6. doi: 10.1136/jmedgenet-2011-100378.
• [10] Fetal akinesia deformation sequence due to a congenital disorder of glycosylation.Am J Med Genet A. 2015 Oct;167A(10):2411-7. doi: 10.1002/ajmg.a.37184. Epub 2015 May 31.
• [11] Massive parallel sequencing identifies RAPSN and PDHA1 mutations causing fetal akinesia deformation sequence.Eur J Paediatr Neurol. 2017 Sep;21(5):745-753. doi: 10.1016/j.ejpn.2017.04.641. Epub 2017 Apr 26.
• [12] Null variants in AGRN cause lethal fetal akinesia deformation sequence.Clin Genet. 2020 Apr;97(4):634-638. doi: 10.1111/cge.13677. Epub 2019 Dec 11.
• [13] Molecular autopsy in maternal-fetal medicine.Genet Med. 2018 Apr;20(4):420-427. doi: 10.1038/gim.2017.111. Epub 2017 Jul 20.
• [14] Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy. Am J Hum Genet. 2008 Dec;83(6):714-24. doi: 10.1016/j.ajhg.2008.10.022. Epub 2008 Nov 20.
• [15] Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited.Birth Defects Res A Clin Mol Teratol. 2009 Aug;85(8):677-94. doi: 10.1002/bdra.20611.
• [16] Metabolic disorders of fetal life: glycogenoses and mitochondrial defects of the mitochondrial respiratory chain.Semin Fetal Neonatal Med. 2011 Aug;16(4):181-9. doi: 10.1016/j.siny.2011.04.010. Epub 2011 May 28.
• [17] 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.
• [18] Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies.Prenat Diagn. 2015 Nov;35(11):1073-8. doi: 10.1002/pd.4648. Epub 2015 Aug 3.
• [19] Mutations in PIGS, Encoding a GPI Transamidase, Cause a Neurological Syndrome Ranging from Fetal Akinesia to Epileptic Encephalopathy. Am J Hum Genet. 2018 Oct 4;103(4):602-611. doi: 10.1016/j.ajhg.2018.08.014. Epub 2018 Sep 27.
• [20] Identification of KLHL40 mutations by targeted next-generation sequencing facilitated a prenatal diagnosis in a family with three consecutive affected fetuses with fetal akinesia deformation sequence.Prenat Diagn. 2016 Dec;36(12):1135-1138. doi: 10.1002/pd.4949. Epub 2016 Nov 18.
• [21] Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. Am J Hum Genet. 2008 Jan;82(1):222-7. doi: 10.1016/j.ajhg.2007.09.016.