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Transient neonatal myasthenia gravis, i.e., TNMG (also termed neonatal myasthenia gravis), is one of the various forms of myasthenia gravis, i.e., MG. MG is an autoimmune disease in which individuals develop or acquire an antibody in their circulating blood that causes easily fatigable (i.e., weakened after relatively little use) skeletal muscles. This antibody interferes with the acetylcholine-induced activation of the acetylcholine receptors located on the neuromuscular junctions of their skeletal muscless. These antibodies bind to the acetylcholine receptor in most cases of MG, the MuSK protein in uncommon cases of MG, the low-density lipoprotein receptor-related protein 4 (i.e., LRP4) in rare cases of MG, or agrin in very rare cases of MG. This binding reduces the ability of acetylcholine receptors to contract skeletal muscles and thereby easy fatigability of the skeletal muscles in certain areas of the body.

MG may cause fatigable muscle weakness in different areas of the body: a) ocular myasthenia gravis has symptoms of skeletal muscle weakness in the eye that cause ptosis (i.e., eye lid drooping), weak eye lid closure, ptosis, i.e. double vision, and/or strabismus, i.e., double vision; b) skeletal muscles of the arms, legs, trunk, and/or head (without involving eye skeletal muscles) with symptoms of finger and wrist extensions, foot and hand dorsiflexion (backward bending or contracting of hand or foot, and difficulty in raising the arms above the head, getting up from low seats or toilets, walking for prolonged distances, and climbing stairs; and c) bulbar (i.e., involving nerves derived from the lower part of the brain stem termed the medulla oblongata) with symptoms such as slurred speech, dysphagia (i.e., difficulty in swallowing), dysphonia (i.e., hoarse voice), bilateral facial nerve weaknesses, jaw weakness, and respiratory muscle weakness which may lead to a myasthenia crisis, i.e., life-threatening respiratory arrest. MG, particularly in long-standing cases, may have two or all three ocular, arm/leg/trunk/head, or bulbar symptoms.

Cause

TNMG is due to the transfer of antibodies against the acetylcholine receptor, MuSK, LRP4, or agrin protein that is circulating in a pregnant mother's blood. This antibody passes through the placenta and into the fetus's circulation. TNMG affects about 1 in 8 children born to mothers who have been diagnosed with myasthenia gravis. In rare cases, a form of TNMG termed fetal acetylcholine receptor inactivation syndrome (also termed FARIS) develops in the fetus. It occura when maternal antibodies to the acetylcholine receptor are directed at the fetal form of this receptor. The fetal and adult acetylcholine receptors consists of 4 subunit proteins, i.e., (α2, β, γ, δ) and (α2, β, ε, δ), respectively, with the fetal form persisting until about the 33rd week of gestation. The mother may not exhibit manifestations of MG because her antibodies are mainly or exclusively targeting fetal receptor. The fetus may exhibit a severe form of TNMG with, for example, arthrogryposis, i.e., congenital joint contractures; esophageal atresia, i.e., the esophagus ending in a pouch rather then entering the stomach; polyhydramnios, i.e., excessive amniotic fluid in the amniotic sac; and fetal death.

Symptoms

Prior to birth, a fetus with TNMG may exhibit akinesia, i.e., reductions in or absent of fetal movements. This finding may be the first evidence that a fetus has this disease. At and after birth, new born infants may show muscle weaknesses which are most prominent in the bulbar muscles of the head and neck that control swallowing, speaking, chewing, and keeping the jaw in place; feeding difficulties; a weak cry; and breathing difficulties which, while uncommon, can range from mild to life-threatening respiratory arrest. The onset of symptoms is often delayed by 6 to 72 hours on in rare cases up to 4 days. This form of the disease is transient, lasting for about three months. However, in some cases, neonatal MG can lead to other health effects, such as arthrogryposis and even fetal death. These conditions are thought to be initiated when maternal AChR antibodies are directed to the fetal AChR and can last until the 33rd week of gestation, when the γ subunit of AChR is replaced by the ε subunit.

In the FARIS form of NNMG, the mother typically does not have symptoms of MG because her antibodies mainly or exclusively target the fetal acetylcholine receptor. The fetus, however may exhibit a severe form of TNMG with, for example, arthrogryposis, i.e., congenital joint contractures; esophageal atresia, i.e., the esophagus ending in a pouch rather then entering the stomach; polyhydramnios, i.e., excessive amniotic fluid in the amniotic sac; and fetal death.