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What

Isaacs’ syndrome is a rare disorder affecting the signaling between nerves and muscles. It is characterized by involuntary muscle contractions, stiffness and cramping (especially in the limbs), increased skin temperature and sweating, and fasciculations. fasciculations are involuntary twitchings of groups of muscle fibers leading to a coarse form of muscle contraction. The involuntary muscle contractions and delayed muscle relaxation persist even during sleep and general anesthesia. The symptoms are caused by abnormal continuous signaling at the end of peripheral nerve fibers that activate muscle fibers.

Who

Isaacs’ Syndrome is a very rare disease. Males and females are equally affected. The age of onset is between 15 and 60 years with most people exhibiting symptoms before age 40.

Signs and Symptoms

People with Isaacs’ syndrome have some or many of the following: 1. Continuous or intermittent muscle twitching 2. Progressive stiffness and inability to relax the muscles 3. Weakened reflexes (also called hyporeflexia) 4. Slurred speech 5. Difficulty chewing and swallowing 6. Difficulty breathing – if muscles of the throat (pharyngeal) or windpipe (laryngeal) are affected 7. Weakness, especially in the lower legs 8. Losing one’s balance when startled 9. Muscle pain, but numbness is uncommon 10. Myokimia, which is a symptom that describes continuous fine vibrating muscle movements that can be seen as undulating under the skin that overlies that muscle group 11. Decreased spontaneous gross motor activity 12. Inability to coordinate voluntary muscle movements (ataxia) and difficulty walking 13. Increased sweating 14. Sometimes Isaacs Syndrome is associated with malignancies of the thymus or lung

Possible Causes

There are hereditary (genetic) and acquired forms of the disorder. The genetic form is called generalized familial neuromyotonia and is inherited in an autosomal dominant pattern, possibly due to a mutation on the short arm of chromosome 12. This means that the child receives one altered gene carrying Isaacs syndrome from one parent to develop the disorder. The acquired forms of Isaacs’ syndrome can classified into 1) focal neuromyotonia where only a certain region of the body is affected or 2) generalized sporadic neuromyotonia where the disease affects the whole body. The acquired forms can result from toxic exposure (for instance, to gold or mercury) or from certain tumors located in the thoracic region (between the neck and the abdomen). They can also occur as an autoimmune disease where the body’s immune system starts to abnormally produce antibodies that target the muscle nerves and thus affect muscle movement.

Diagnosis

Isaacs’ syndrome is diagnosed based on the patient’s past medical history, physical exam and electromyography (EMG). EMG is used to record electrical activity in the muscles and is abnormal in patients with Isaacs’ syndrome. Analysis of cerebrospinal fluid, which can be obtained by lumbar puncture, may help confirm the diagnosis. Diagnosis can also be made through identification of the abnormal auto-antibodies that are targeting the muscle nerves and affecting muscle movement.

Treatment

There is no cure or specific treatment for this disorder. However, treatments for some of the symptoms are available. Anticonvulsant medications, like phenytoin, low dose acetazolamide, and carbamazepine may prevent the symptoms from occurring by stopping the abnormal impulses. Immunosuppressive therapy is used in individuals in whom the autoimmune form of the disorder is suspected. Plication of the diaphragm (procedure that puts folds or tucks in the main muscle that controls breathing) to help patients breathe is used to treat some individuals. Ongoing research includes looking into other possible treatments like oxygen inhalation (to help muscle relaxation and hand spasms) and surgery to block motor nerves and sensory nerves that control the muscle unit. Therapies that have been used without success include steroids, calcium, barbiturates, diazepam, IVIG and quinidine.

Prognosis

While there is as yet no cure for this disease, management of patient’s symptoms is available. Long term prognosis is uncertain at this time (research is scarce since the disease is very rare).

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

National Institute of Neurological Disoders and Stroke
A well written summary of the syndrome with other helpful information on the website.

CancerWeb Project
From the Dept of Medical Oncology, University of Newcastle on Tyne, this site offers a short definition of the syndrome with links to many medical terms.

Clinical Trials.gov
A website with links to ongoing clinical trials.

Google Search for Isaac's Syndrome

References and Sources

1. Isaacs’ Syndrome. www.bchealthguide.org/kbase/nord/nord758.htm 2. What is Isaacs’ Syndrome? www.ohiohealth.com/healthreference/reference/FADB0EBD-B204-4D92-AF51978B7119F909.htm?category=6303 3. A Review of Isaacs’ Syndrome. neuro-www.mgh.harvard.edu/forum_2/ParkinsonsDiseaseF/Isaacssyndrome.html 4. What is Isaacs’ Syndrome? ; Is there any treatment? ; What is the prognosis?. www.ninds.nih.gov/health_and_medical/disorders/isaacs_syndrome.htm