Rare Myasthenic Syndromes
Reviewed by: HU Medical Review Board | Last reviewed: May 2021 | Last updated: October 2022
Myasthenic syndromes are conditions that cause problems with the communication between nerves and muscles. These are rare diseases of the neuromuscular junction, similar to myasthenia gravis (MG), but are actually different diseases. Only a few hundred people in the United States are known to have these myasthenic syndromes:1-4
- Lambert-Eaton myasthenic syndrome (LEMS)
- Neuromyotonia (Isaacs’ syndrome)
- Congenital myasthenic syndrome
Some myasthenic syndromes are hereditary, meaning a person inherited genes that cause these conditions. Some are not.
Lambert-Eaton myasthenic syndrome
About 400 people in the United States are known to have Lambert-Eaton myasthenic syndrome (LEMS). The first LEMS symptoms usually include muscle weakness in the thighs followed by the shoulders. This weakness grows slowly over weeks or months and often spreads to other muscles in the:
- Arms and hands
- Legs and feet
- Face and neck
Other symptoms include:1
- Dry mouth
- Dry eyes
- Decreased sweating
LEMS is caused by antibodies that interfere with communication between the nerve and muscle.
About 6 out of 10 people with LEMS also have small cell lung cancer (SCLC). LEMS and SCLC tend to be found in men over age 60 years who have a history of smoking. These men often develop LEMS and muscle weakness months or years before being diagnosed with small cell lung cancer.1
However, LEMS may also occur in people who do not have cancer. This happens most often in younger adults often who have a personal or family history of autoimmune disease. These people normally develop LEMS around age 35 and do not develop lung cancer. LEMS is extremely rare in children, with only 11 known cases.1
Isaacs’ syndrome is also called neuromyotonia or peripheral nerve hyperexcitability. Symptoms gradually increase and include muscle cramps, twitching, stiffness, and weakness. The muscle twitches occur all day and night, and even under general anesthesia.2
Isaacs’ syndrome is so rare that little is known about the condition. Doctors believe that both a hereditary and acquired form may exist. In some people a thymoma, small cell lung cancer, or Hodgkin lymphoma may occur at the same time. It most often begins before age 40. Other symptoms include:3
- Increased sweating
- Lack of muscle coordination
- Confusion, memory loss, hallucinations
Congenital myasthenic syndromes
Congenital myasthenic syndromes (CMS) are a group of rare conditions that cause muscle weakness in newborns, infants, or young children. All CMS feature muscle weakness that gets worse with activity. The muscles most often affected include:4
- Arms and legs
Weakness in these muscles may make it hard for the child to learn to walk or speak.
The muscle weakness can be mild to severe. It can be constant in some children but come and go in others. In some children it gets worse over time, while in others the muscle weakness happens only sometimes.
These syndromes are caused by mutations in at least 32 different genes. Genetic testing is needed to tell which subtype of CMS a person has. Treatment can be very different depending on the subtype.4
Between 2 and 12 children per 1 million may have CMS. Because CMS is so rare and there are so many subtypes, it is hard to know what the long-term outcome is for children with congenital myasthenic syndromes.4