Case reportFetal acetylcholine receptor inactivation syndrome and maternal myasthenia gravis: A case report
Introduction
A small proportion (<10%) of infants born to mothers with myasthenia gravis (MG) develop, at birth, transient neonatal myasthenic syndrome (NMG) [1]. The severity of NMG is highly variable but generally there is recovery within 4–5 weeks. In the last few years there have been reports of an unusual phenotype in newborns of myasthenic mothers. This is characterized by severe hypotonia and swallowing difficulties at birth followed by partial improvement but persistence of generalized weakness particularly in the bulbar and facial muscles [2], [3]. Oskoui et al. [4] reported three consecutive brothers born to a myasthenic mother. Although in all three the severe neonatal hypotonia and difficulty in swallowing had resolved by 5–6 weeks, facial diplegia associated with a high-arched palate and velopharyngeal incompetence persisted. The maternal fetal/adult acetylcholine receptor antibodies (AChR-Abs) ratio was very high and the authors suggest that the inactivation of fetal AChR impaired fetal movements during development resulting in permanent defects in vulnerable muscles. Here we report a similar case who unfortunately died unexpectedly.
Section snippets
Case report and results
The girl was the first child of a myasthenic mother. The mother underwent thymectomy some years before pregnancy, and during pregnancy was asymptomatic, with only neostigmine treatment. Her family history was negative for malformations, neurological disorders, consanguinity or abortion. The infant was born at 38 weeks of gestational age after an uncomplicated pregnancy and spontaneous vaginal delivery (Apgar 8–9). Both amniotic fluid and fetal movements, monitorized from 24 weeks, were referred
Discussion
NMG occurs in a small proportion of infants born to MG mothers with myasthenia gravis and although the severity of symptoms is highly variable, generally there is recovery within 4–5 weeks. It is not clear why some infants are born with NMG while others remain asymptomatic; specificity of the maternal antibodies for the fetal form of the acetylcholine receptor may be involved [6]. The nicotinic AChR at the neuromuscular junction of striated muscle is composed of five subunits. During
References (13)
- et al.
Maturation of acetylcholine receptor in skeletal muscle: regulation of the AChRgamma-to-epsilon-switch
Dev Biol
(1996) - et al.
Recurrent congenital arthrogryposis leading to a diagnosis of myasthenia gravis in an initially asymptomatic mother
Neuromuscul Disord
(1995) - et al.
Arthrogryposis multiplex congenita with maternal autoantibodies specific for a fetal antigen
Lancet
(1995) - et al.
Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome
Am J Hum Genet
(2006) - et al.
Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit
Am J Hum Genet
(2006) - et al.
Acquired autoimmune myasthenia gravis
Cited by (20)
Clinical and pathophysiologic relevance of autoantibodies in neonatal myasthenia gravis
2021, Pediatrics and NeonatologyCitation Excerpt :Neonatal MG is commonly a transient condition; maternal antibodies commonly bind to both fetal and adult types of AChRs. However, infants born to mothers with antibodies that selectively inhibit the function of the fetal type of AChR may cause severe and persistent myopathic features, often with fetal arthrogryposis; this is known as fetal AChR inactivation syndrome.24 MuSK-MG has a higher prevalence in women in their twenties and thirties.25
Neuromuscular disorders in pregnancy
2020, Handbook of Clinical NeurologyCitation Excerpt :There are some exceptional cases of antibodies to the fetal AChR γ subunit that can result in severe or sometimes fatal fetal arthrogryposis (Vincent et al., 1995; Oskoui et al., 2008). This form is now known as fetal AChR inactivation syndrome (D’Amico et al., 2012). AChR seropositive MG is commonly associated with transient neonatal MG; however, other forms, notably MuSK patients, have been reported.
Neonatal hypotonia and neuromuscular conditions
2019, Handbook of Clinical NeurologyCitation Excerpt :There is generally a good response to anticholinesterases. The severity of signs of neonatal myasthenia is not always related to the severity or duration of maternal disease (D'Amico et al., 2012). The term congenital myasthenic syndromes includes a heterogeneous group of hereditary disorders affecting the neuromuscular junction due to one or more specific mechanisms (Souza et al., 2016; McMacken et al., 2017, 2018; Natera-de Benito et al., 2017; Nicole et al., 2017).
Hypotonia and Weakness: Levels Above the Lower Motor Neuron
2018, Volpe's Neurology of the NewbornMyasthenia Gravis
2016, Encyclopedia of ImmunobiologyArthrogryposis
2015, Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach