Transient neonatal myasthenia gravis

Causes

TNMG is caused by maternal antibodies against the adult nicotinic acetylcholine receptor (nAChR) in about 85% of cases, against the MuSK protein in about 6% of cases, and against LRP4 in many of the remaining cases. These antibodies pass from the mother's blood through the placenta into the fetus's circulation and tissues. The condition affects roughly one in eight children born to mothers diagnosed with myasthenia gravis and has also been reported in offspring of mothers whose MG is in remission. In rare instances, the FARIS form develops when maternal antibodies target the fetal form of nAChR, which differs from the adult form by having a gamma subunit instead of an epsilon subunit; the fetal form persists until about the 33rd week of gestation.

Symptoms

A fetus or newborn is likely to have TNMG if a sibling was previously diagnosed with it, or if the offspring of a mother with MG shows reduced, rapidly declining, or absent fetal movements. Fetal movements are first perceived by the mother between the 16th and 20th weeks of pregnancy, peaking by 29 to 38 weeks; a sharp decline or lack of movements signals serious abnormalities. About half of TNMG cases show symptoms at birth, while the remainder appear 6 to 72 hours later, sometimes up to several days after birth, possibly due to immunosuppressive effects of alpha-fetoprotein or transfer of cholinesterase inhibitors from the mother.

Affected newborns typically exhibit skeletal muscle hypotonia and weakness most prominent in head and neck muscles, causing facial diplegia, reduced swallowing control, weak crying, sucking, and chewing, inability to keep the jaw in place, feeding difficulties, and breathing difficulties that rarely require mechanical ventilation. Some infants develop jaundice, likely from inadequate fluid intake. In most cases, dysfunctions improve and resolve within 3 to 4 months as maternal antibodies dissipate.

Diagnosis

Congenital myasthenic syndrome (CMGS) and juvenile myasthenia gravis (JMG) must be distinguished from TNMG. CMGS is an inherited genetic disease without circulating antibodies to adult nAChR, MuSK, or LRP4. JMG involves such antibodies but never presents before 8 months of age.

Classic TNMG symptoms in the offspring of a mother with MG are considered sufficient for diagnosis. However, about 88% of offspring of mothers with MG do not have TNMG, and some affected newborns lack clear clinical abnormalities. In such cases, identification of antibodies to adult nAChR, MuSK, LRP4, or fetal nAChR in the offspring's circulation is the definitive diagnostic standard.

Treatment

Women with MG should receive standard prenatal care including regular fetal growth assessments, self-monitoring of fetal movements starting at 24 weeks, and ultrasound scans before 24 weeks. Newborns of mothers with MG require close monitoring for respiratory depression. A review of 147 TNMG cases found that 4 days of hospital monitoring sufficed to detect respiratory depression and other serious complications. Treatment is mainly supportive and depends on symptom severity, ranging from small oral feedings to mechanical ventilation, with the understanding that symptoms typically resolve within 3 to 4 months.

A recent review recommended treatments based on severity: a positive pharmacological challenge test with neostigmine, intravenous immunoglobulin therapy, or plasmapheresis. Newborns undergoing mechanical ventilation should not receive acetylcholinesterase inhibitors, as these may increase airway secretions and impair ventilation.