Information on the following diseases can be found in the Related Disorders section of this report:

• Epilepsy
• Lennox-Gastaut Syndrome
• Myoclonus

West syndrome is a type of epilepsy characterized by early onset of spasms, abnormal brain wave patterns called hypsarrhythmia and sometimes mental retardation.

Symptoms associated with West syndrome usually begin during the first year of life. West syndrome is characterized by involuntary muscle spasms that occur due to episodes of uncontrolled electrical disturbances in the brain (seizures). Each involuntary spasm typically begins suddenly and lasts for only a few seconds and occur usually in clusters that can last entirely over 10-20 minutes. Such episodes, which may occur upon awakening or after feeding, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.

Infants with West syndrome also have severe electroencephalogram (EEG) spike wave patterns (hypsarrhythmia), and delays in acquiring skills that require coordination of muscles and voluntary movements (psychomotor retardation).

Children with West syndrome usually develop recurrent epileptic seizures as they age. The syndrome often develops into the Lennox-Gastaut form of epilepsy with seizures that are difficult to control, making early diagnosis very important. (For more information on Lennox-Gastaut syndrome, see the Related Disorders section below.)

A specific cause for West syndrome can be identified in approximately 70-75% of those affected (symptomatic). Any disorder that can lead to brain damage can be an underlying cause of West syndrome including trauma, brain malformations, infections, metabolic diseases, chromosomal abnormalities such as Down syndrome, several different genetic diseases, and an abnormality (mutation) in the ARX gene or STK9 gene located on the X chromosome.

The most common disorder responsible for West syndrome is tuberous sclerosis complex. (TSC). TSC is an autosomal dominant genetic condition associated with seizures, eye, heart and kidney tumors and skin findings.

Other genetic disorders that can result in West syndrome include Sturge-Weber syndrome, incontinentia pigmenti, pyroxidine dependency, non-ketotic hyperglycemia, maple syrup urine disease, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency.

X-linked West syndrome can be caused by a mutation in the STK9 gene or the ARX gene in the X chromosome. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

West syndrome is a rare neurological syndrome that can affect males and females. The X-linked form of West syndrome affects males more often than females.

West syndrome has been estimated to affect 2.5 to 6 of every 10,000 live births in the United States. West syndrome accounts for approximately 30 percent of all cases of epilepsy affecting infants.

Symptoms of the following disorders can be similar to those of West syndrome. Comparisons may be useful for a differential diagnosis:

Epilepsy is a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks are frequently preceded by an "aura", a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. There are many different types of epilepsy and the exact cause is generally unknown. (For more information on this disorder, choose "epilepsy" as your search term in the Rare Disease Database.)

Lennox-Gastaut syndrome (LGS) is a rare disorder that typically becomes apparent during infancy or early childhood. The disorder is characterized by frequent episodes of uncontrolled electrical disturbances in the brain (seizures) and, in many cases, abnormal delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation). Individuals with the disorder may experience several different types of seizures. Lennox-Gastaut syndrome may be due to, or occur in association with, a number of different underlying disorders or conditions. (For more information on this disorder, choose "Lennox-Gastaut" as your search term in the Rare Disease Database.)

Myoclonus is a neurological movement disorder in which there are sudden involuntary muscle contractions. There are many different types of myoclonus including some that are hereditary. Other causes include lack of oxygen, viral, malignancies, and lesions of the central nervous system along with drugs and metabolic disorders. (For more information on this disorder, choose "myoclonus" as your search term in the Rare Disease Database.)

The first step in the treatment of West syndrome is to characterize the patterns of brain activity through measurement with various devices. Among these are:

Electroencephalography (EEG):
This is a painless and non-intrusive means of recording the patterns of electrical activity of the brain. Electrodes placed on the scalp pick up and record the electrical waves during periods of activity and, with luck, during periods of sleep.

Brain Scans, including four scanning methods:

Computed Tomography (CT). Harnessing X-rays to a computer generates pictures of cross-sections of the brain from which the detail of development may be determined. CT is also very good at showing areas of calcification that in some cases, may be essential for the diagnosis.

Magnetic Resonance Imaging (MRI). This instrument produces detailed images of cross-sections or slices of the brain by using the magnetic properties of particular atoms found in the brain.

Proton Emission Tomography (PET). Not yet in as widespread use as any of the above, PET scans, which involve a linear accelerator and even more sophisticated electronics, offer another technique with which to investigate brain activity. PET is especially productive in allowing the investigator to follow metabolic and energy activity in the brain.

Infection as a source of infantile spasms may be determined by blood tests, urine tests and lumbar puncture.

A Wood's lamp is used to examine skin for lesions with lack of skin color in order to determine if tuberous sclerosis is a possible diagnosis.

Molecular genetic testing is available for mutations in the ARX gene associated with X-linked West syndrome. It is also available for Tuberous Sclerosis Complex.

Treatment
The treatment of West syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

In some cases, it is possible that treatment with anticonvulsant drugs may help reduce or control various types of seizure activity associated with West syndrome. Such medications include, adrenocorticotropic hormone (ACTH), prednisone, vigabatrin and pyridoxine. If these treatments are not successful, other medications such as benzodiazepines, valproic acid, lamotrigine, topiramate and zonisamide may be used. Finally, in cases where there is a malformation or tuberous sclerosis complex, epilepsy surgery may be helpful as a last ditch effort to control spasms.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

McKusick VA., ed. Online Mendelian inheritance in man, (OMIM). Baltimore, MD; Johns Hopkins University Press; Entry No: 308350; Last Update:8/20/2007

TEXTBOOKS
Susan Koh, MD. Infantile Spasms. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003: 541.

Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1402, 1405.

Menkes JH, au, Pine JW, et al, eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:744-748.

Adams, RD, et al, eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:323, 332.

REVIEW ARTICLES
Gatti G, et al. The new antiepileptic drugs: pharmacological and clinical aspects. Curr Pharm Des. 2000;6:839-860.

Fejerman N, et al. Vigabatrin as a first-choice drug in the treatment of West syndrome. J Child Neurol. 2000;15:161-65.

Morton LD, et al. Overview of childhood epilepsy and epileptic syndromes and advances in therapy. Curr Pharm Des. 2000;6:879-900.

JOURNAL ARTICLES
Kato M. A new paradigm for West syndrome based on molecular and cell biology. Epilepsy Res. 2006; 70 Suppl 1:S87-95.

Sherr EH. The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. Curr Opin Pediatr. 2003;15(6):567-71.

Ito M, et al. Low-dose ACTH therapy for West syndrome: Initial effects and long-term outcome. Neurology. 2002;58:110-14.

Elterman RD, et al. Randomized trial of vigabatrin in patients with infantile spasms. Neurology. 2001;57:1416-21.

Fukuyama Y. History of classification identification of West syndrome - in quest after the classic. Brain Dev. 2001;23:779-87.

Appleton RE. West syndrome: long-term prognosis and social aspects. Brain Dev. 2001;23:688-91.

Riikonen R. Long-term outcome of patients with West syndrome. Brain Dev.2001;23:683-87.

Asano E, et al. Surgical treatment of West syndrome. Brain Dev. 2001;23:668-76.

Hancock E, et al. The treatment of West syndrome: a Cochrane review of the literature to December 2000. Brain Dev. 2001;23:624-34.

Salonga AM, et al. West syndrome: the Philippine experience. Brain Dev. 2001;23:616-23.

Haas-Lude K, et al. Acute encephalopathy associated with vigabatrin in a six-month-old girl. Epilepsia. 2000;41:68:30.

Ito M, et al. Subdural hematoma during low-dose ACTH therapy in patients with West syndrome. Neurology. 2000;54:2346-2347.

Glauser TA, et al. Long-term response to piamate in patients with West syndrome. Epilepsia. 2000; 41 Suppl 1:S91-94.

Datta AN, et al. Prognosis of seizures occuring in the first year. Pediatr Neurol. 2000;22:386-391

Gaily E, et al. Cognitive deficits after cryptogenic infantile spasms with benign seizure evolution. Dev Med Child Neurol. 1999;41:660-664.

Appleton RE, et al. Randomized, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia. 1999;40:1627-33.

INTERNET:
eMedicine - Infantile Spasm (West Syndrome) : Article by Tracy A Glauser MD
http://www.emedicine.com/neuro/topic171.htm