Neuromuscular Junction Disorders in Neonates and Infants

Movement depends on a signal being carried from the brain to the muscle.  There are many potential stops along the way: the spinal cord, the peripheral nerve, the space between the nerve and the muscle, and the muscle itself.  The space between the nerve and muscle is called the neuromuscular junction.  There, a neurotransmitter called acetylcholine crosses a short gap, and is received by special receptors.

 When the transmitter hits the receptor, the signal to contract is received. 

Unfortunately, sometimes things go wrong.  The most common example is myasthenia gravis. Myasthenia gravis is an autoimmune disease, meaning it’s caused by the body’s immune system attacking the body itself.  In the case of myasthenia gravis, the immune system attack the neuromuscular junction.  Most myasthenia gravis results from antibodies attacking the receptor for acetylcholine.

Most of the time, myasthenia gravis is thought to affect young women and older men, but the disorder can also impact the very, very young. There are three main forms of  myasthenia gravis in infants and neonates.

Transitory Neonatal Myasthenia

Mothers with myasthenia gravis sometimes pass those antibodies to their children.  In about 20 percent of children with myasthenic mothers, the antibodies cross the placenta and enter the fetus.  Among those mothers who have a child with transitory neonatal myasthenia, the chance of future children developing the disorder is about 75 percent.

Children with transitory neonatal myasthenia are weak from birth.  The muscles are flaccid, and the child may not feed as well as they need to.  If the weakness is severe enough, treatment may be needed with plasmapheresis to remove the antibody.

The diagnosis is confirmed by giving a cholinesterase inhibitor to increase levels of acetylcholine and watch for improvement.

  The disease is managed by supporting feeding with a nasogastric tube if needed.  Drugs such as neostigmine can also be given before feeding.

The good news is that this form of neonatal myasthenia is transitory.  Ninety percent of children fully recover by the time they are two months old.

Congenital Myasthenia

This form of myasthenia gravis is genetic, and usually inherited in an autosomal recessive fashion, meaning that parents may never have had the symptoms of concern.  Those symptoms include facial weakness that develops at birth.  Signs can include difficulty opening the eyes or moving the eyes appropriately. 

Congenital myasthenia can be caused by abnormal release of acetylcholine from the nerves or by problems with the receptors on the muscle.  Unlike other forms of myasthenia gravis, this is not an autoimmune disease.   

No immunosuppressant medications are used in the treatment.  If the cause is due to decreased acetylcholine release, medications such as pyridostigmine can be used to increase the levels of acetylcholine in the neuromuscular junction.


Familial Infantile Myasthenia

Familial infantile myasthenia is associated with polymorphisms on chromosome 17.  Symptoms are present from birth, and include poor feeding and respiratory failure.  This form of myasthenia gravis can be very severe, and sudden infant death may result.  Symptoms generally improve iwht age, however, and the disease may respond to cholinesterase inhibitors, which increase levels of acetylcholine in the neuromuscular junction. 

Other Neuromuscular Problems in Newborns

Too much magnesium in the blood can block calcium release in motor neurons.  This leads to diminished release of acetylcholine.  The most common cause is magnesium sulfate given to the mother.  Certain antibiotics, such as aminoglycosides, can also interfere with transmission at the neuromuscular junction. 

Botulism is a very serious disorder in children caused by toxins produced by the clostridium botulinum bacteria.  Cases may result from eating wild honey or home canned food containing botulinum sores.  Infants usually present at first with constipation and poor feeding, but then symptoms progress into general weakness.  Symptoms may become life threatening, requiring mechanical ventilation in order to support breathing.   Botulism should be suspected in any infant who has sudden onset of inability to open the eyes, diminished activity, constipation and a weak suck, especially  if they’ve potentially been exposed based on their history.  A antitoxin is available, and should be administered as soon as possible.  Botulism is an emergency, requiring immediate hospitalization. 


Olaf A Bodamer, Neuromuscular Disorders in newborns and Infants.  UpToDate Updated. December 4, 2014, Accessed February 24, 2015. 

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