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Case Reports
. 2019 Nov 6;7(21):3655-3661.
doi: 10.12998/wjcc.v7.i21.3655.

Compound Heterozygous Mutation of MUSK Causing Fetal Akinesia Deformation Sequence Syndrome: A Case Report

Free PMC article
Case Reports

Compound Heterozygous Mutation of MUSK Causing Fetal Akinesia Deformation Sequence Syndrome: A Case Report

Na Li et al. World J Clin Cases. .
Free PMC article


Background: Fetal akinesia deformation sequence (FADS) is a broad spectrum disorder with absent fetal movements as the unifying feature. The etiology of FADS is heterogeneous and mostly still unknown. A prenatal diagnosis of FADS relies on clinical features obtained by ultrasound and fetal muscle pathology. However, the recent advances of next-generation sequencing (NGS) can effectively provide a definitive molecular diagnosis.

Case summary: A fetus presented after 24 wk and 6 d of gestation with absent fetal movements and multiple abnormal ultrasonographic signs. The mother had had a previous abortion due to a similarly affected fetus a year before. A clinical diagnosis of FADS was made. The parents refused cord blood examination and chose abortion. A molecular diagnosis of fetal muscle using NGS of genes found a compound heterozygous mutation in the MUSK gene: c.220C > T (chr9: 113449410 p.R74W) and c.421delC (chr9: 113457745 p.P141fs).

Conclusion: To our knowledge, this is the first report in China showing that a mutation in MUSK is associated with FADS. This supports previous finding that a lethal mutation of MUSK will cause FADS. A precise molecular diagnosis for genetic counseling and options for a prenatal diagnosis of FADS are very important, especially for recurrent FADS; this may also provide evidence for both prenatal and preimplantation genetic diagnoses.

Keywords: MUSK gene; Case report; Fetal akinesia deformation sequence; Joint contractures.

Conflict of interest statement

Conflict-of-interest statement: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.


Figure 1
Figure 1
An affected family history pedigree. Ultrasound and genetic data revealed a frameshift mutation in muscle, skeletal receptor tyrosine kinase. A: Pedigree of affected family highlights two affected fetuses; B: Photograph of a fetus with fetal akinesia deformation sequence (FADS) from the second pregnancy after an abortion at 25 gestational weeks; C: The second pregnancy displayed polyhydramnios fetal hydrops and micrognathia; D: Sanger sequencing revealed that the mother and father had different heterozygous mutations, and the fetus had a compound heterozygous mutation; E: Mutation sites of c.421delC and c.220C > T in each species and conserved region; F: Mutation sites of Pro141Hisfs*15 and p. R74W in each species and conserved region; G: Domain structure of muscle, skeletal receptor tyrosine kinase (MUSK) protein and other mutations in MUSK previously reported to cause FADS.
Figure 2
Figure 2
Histological, immunohistochemical, and Western blot findings. A: Tissues from the affected fetus; A i: Hematoxylin and eosin staining showed a large variation in muscle fiber size, with many atrophic fibers and increased amounts of loose connective tissue; A ii: Immunohistochemistry with antibody against slow myosin demonstrated only a few scattered type 1 fibers; A iii: Immunohistochemistry with antibody against fast myosin demonstrated that the majority were muscle fibers; B: The results for a control fetus (dead fetus after a spontaneous abortion after the same number of gestational weeks); C: Western blot indicating that the amount of fast myosin heavy chain was significantly higher in the muscles of the affected fetus compared to the control fetus. The loading control is GAPDH. P < 0.05.

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    1. Moessinger AC. Fetal akinesia deformation sequence: an animal model. Pediatrics. 1983;72:857–863. - PubMed
    1. Hall JG. Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. Birth Defects Res A Clin Mol Teratol. 2009;85:677–694. - PubMed
    1. Ravenscroft G, Sollis E, Charles AK, North KN, Baynam G, Laing NG. Fetal akinesia: review of the genetics of the neuromuscular causes. J Med Genet. 2011;48:793–801. - PubMed
    1. Wilbe M, Ekvall S, Eurenius K, Ericson K, Casar-Borota O, Klar J, Dahl N, Ameur A, Annerén G, Bondeson ML. MuSK: a new target for lethal fetal akinesia deformation sequence (FADS) J Med Genet. 2015;52:195–202. - PubMed
    1. Tan-Sindhunata MB, Mathijssen IB, Smit M, Baas F, de Vries JI, van der Voorn JP, Kluijt I, Hagen MA, Blom EW, Sistermans E, Meijers-Heijboer H, Waisfisz Q, Weiss MM, Groffen AJ. Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence. Eur J Hum Genet. 2015;23:1151–1157. - PMC - PubMed

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