Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 17;13(4):1136.
doi: 10.3390/jcm13041136.

Transient Neonatal Myasthenia Gravis as a Common Complication of a Rare Disease: A Systematic Review

Jenny Linnea Victoria Lindroos  1   2 , Marte-Helene Bjørk  1   2 , Nils Erik Gilhus  1   2
Affiliations
Review

Transient Neonatal Myasthenia Gravis as a Common Complication of a Rare Disease: A Systematic Review

Jenny Linnea Victoria Lindroos et al. J Clin Med. .

Abstract

Myasthenia gravis (MG) is a rare autoimmune disease. Transient neonatal myasthenia gravis (TNMG) is caused by pathogenic maternal autoantibodies that cross the placenta and disrupt signaling at the neuromuscular junction. This is a systematic review of this transient immunoglobulin G (IgG)-mediated disease. TNMG affects 10-20% of children born to mothers with MG. The severity of symptoms ranges from minor feeding difficulties to life-threatening respiratory weakness. Minor symptoms might go unnoticed but can still interfere with breastfeeding. Acetylcholine-esterase inhibitors and antibody-clearing therapies such as immunoglobulins can be used to treat TNMG, but most children do well with observation only. TNMG is self-limiting within weeks as circulating antibodies are naturally cleared from the blood. In rare cases, TNMG is associated with permanent skeletal malformations or permanent myopathy. The mother's antibodies can also lead to spontaneous abortions. All healthcare professionals meeting pregnant or birthing women with MG or their neonates should be aware of TNMG. TNMG is hard to predict. Reoccurrence is common among siblings. Pre-pregnancy thymectomy and intravenous immunoglobulins during pregnancy reduce the risk. Neonatal fragment crystallizable receptor (FcRn) blocking drugs for MG might reduce TNMG risk.

Keywords: MuSK antibodies; acetylcholine receptor antibodies; autoantibodies; maternal–fetal exchange; myasthenia gravis; neonatal disease; neuromuscular junction.

PubMed Disclaimer

Conflict of interest statement

M.H. Bjørk received speaker honoraria and/or served on scientific advisory boards for Teva, Eisai, AbbVie, Pfizer, Novartis, Lundbeck, Angelini Pharma, Jazz pharmaceuticals, and Lilly over the last 5 years. None of the assignments concerned treatment of myasthenia gravis. N.E. Gilhus received financial support from UCB, Argenx, Janssen, Merck, Roche, Alexion, Immunovant, Huma, Denka, Grifols, and Dianthus. J. Lindroos; declare no conflicts of interest.

Figures

Figure A1
Figure A1
PRISMA flow diagram.
Figure 1
Figure 1
Pathogenic mechanisms of immunoglobulin G (IgG) antibodies (depicted in purple, pink and red) against the acetylcholine receptor (AChR), in relation to the fetal/adult AChR subunit structure, localization of the main immunogenic region (MIR), and the acetylcholine (Ach) binding site.
Figure 2
Figure 2
Antibodies against MuSK inhibit the formation of the MuSK-LRP4-Agrin complex and prevent the activation of intracellular pathways that normally lead to AChR clustering. MuSK is also responsible for anchoring acetylcholine-esterase to the postsynaptic membrane. Abbreviations: MuSK; muscle-specific kinase. LRP4; low-density lipoprotein receptor-related protein 4. AChR; acetylcholine receptor. Ach; acetylcholine. AChE; acetylcholine esterase. ColQ; collagen-like tail subunit of asymmetric acetylcholinesterase.
Figure 3
Figure 3
Neonatal fragment crystallizable receptor (FcRn)-dependent transmission of pathological IgG from mother to child and AChR antibody targets (fAChR depicted in light blue-grey and adAChR depicted in dark blue-grey) according to the fetal/neonatal developmental stage, illustrating the mechanisms for the disease transfer of maternal MG in TNMG. Abbreviations: gw; gestational week.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Gilhus N.E., Hong Y. Maternal myasthenia gravis represents a risk for the child through autoantibody transfer, immunosuppressive therapy and genetic influence. Eur. J. Neurol. 2018;25:1402–1409. doi: 10.1111/ene.13788. - DOI - PubMed
    1. Gilhus N.E. Myasthenia Gravis Can Have Consequences for Pregnancy and the Developing Child. Front. Neurol. 2020;11:554. doi: 10.3389/fneur.2020.00554. - DOI - PMC - PubMed
    1. Ohlraun S., Hoffmann S., Klehmet J., Kohler S., Grittner U., Schneider A., Heuschmann P.U., Meisel A. Impact of myasthenia gravis on family planning: How do women with myasthenia gravis decide and why? Muscle Nerve. 2015;52:371–379. doi: 10.1002/mus.24556. - DOI - PubMed
    1. Haddaway N.R., Page M.J., Pritchard C.C., McGuinness L.A. PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Syst. Rev. 2022;18:e1230. doi: 10.1002/cl2.1230. - DOI - PMC - PubMed
    1. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst. Rev. 2021;10:89. doi: 10.1186/s13643-021-01626-4. - DOI - PMC - PubMed

LinkOut - more resources