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West syndrome

NORD is very grateful to Susan Koh, MD, Associate Professor, Department of Pediatrics and Neurology, University of Colorado School of Medicine; Director of the Pediatric Epilepsy Program, Children's Hospital of Colorado, for assistance in the preparation of this report.

Synonyms of West syndrome

  • epileptic spasms
  • infantile spasms

Disorder Subdivisions

  • x linked infantile spasms

General Discussion

West syndrome is a type of epilepsy characterized by spasms, abnormal brain wave patterns called hypsarrhythmia and sometimes mental retardation. The spasms that occur may range from violent jackknife or "salaam" movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. They can also occur rarely in older patients; if this happens, they are called "epileptic spasms" rather than infantile spasms. There are many different causes of West syndrome and if a specific cause can be identified, a diagnosis of symptomatic West syndrome can be made. If a cause cannot be determined, a diagnosis of cryptogenic West syndrome is made.

Symptoms

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 occurs 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).

Approximately a third of children with West syndrome may develop recurrent epileptic seizures as they age. The syndrome often develops into the Lennox-Gastaut syndrome with mixed types of seizures that are difficult to control and mental retardation. (For more information on Lennox-Gastaut syndrome, see the Related Disorders section below.). Approximately another third of children with West syndrome will continue to have epileptic spasms at an older age group. The last third of patients will have spasms that resolve with time, usually in patients who have no clear etiology.

Causes

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 such as hemimegalencephaly or cortical dysplasia, infections, chromosomal abnormalities such as Down syndrome, neurocutaneous disorders such as tuberous sclerosis complex (TSC), Sturge Weber syndrome, incontinentia pigmenti, several different metabolic/genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup urine disorder, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency, Otahara’s syndrome, and an abnormality (mutation) in the ARX gene or CDKL5 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.

X-linked West syndrome can be caused by a mutation in the CDKL5gene 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.

Affected Populations

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.

Related Disorders

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.)

Standard Therapies

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. If a pattern called hypsarrhythmia is noted, especially during sleep, this can help to suggest that a patient has infantile spasms. However, there are times when a patient may have infantile spasms and does not have the hypsarrhythmia pattern due to a lag time between clinical symptoms and EEG pattern. Therefore, an overnight, long term video EEG monitoring is preferable compared to a routine 20 minute EEG study in some cases of infantile spasms.

Brain Scans, such as:

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. However, this does not provide as detailed a picture as a MRI.

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.

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 and CDKL5 genes associated with X-linked West syndrome. It is also available for tuberous sclerosis complex. Some genetic disorders will require CSF fluid for genetic testing such as in nonketotic hyperglycemia which may require CSF samples to test for glycine as well as mitochondrial diseases which may require CSF to test for lactate. A genetic mutation of STXBP1 has recently been noted in patients with Otahara’s syndrome as well.

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. The benefits of the medication need to be weighed with the side effects of each treatment. For example, ACTH and other steroids are known to cause issues with immunosuppression, hypertension, gastric issues, agitation and irritability, glucose in the urine, etc. Vigabatrin may cause an irreversible visual field defect, irritability, and transient hyperintensity of deep structures in the MRI. In a recent multicenter study looking at steroid treatment compared to vigabatrin, it was felt that steroids may have better seizure control compared to vigabatrin at 2 weeks of treatment, but that the effectiveness was the same after a year. In addition, vigabatrin was more effective in patients with tuberous sclerosis or cortical dysplasia compared to steroids. It is felt that a quicker time between diagnosis and treatment will have less deleterious effect on the development compared to a longer lead time. If these treatments are not successful, other medications such as benzodiazepines, valproic acid, topiramate, rufinamide and zonisamide may be used. Ketogenic diet has also been successful at times in the treatment of infantile spasms. 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.

Investigational Therapies

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:

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

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Contact for additional information about West syndrome:

Susan Koh, MD
Director of the Epilepsy Program
Children's Hospital of Colorado
Associate Professor of Pediatrics and Neurology
University of Colorado School of Medicine
720-777-6895
susan.koh@childrenscolorado.org

Organizations related to West syndrome

References

REVIEW ARTICLES
Pellock JM, et al. Infantile spasms: a US consensus report. Epilepsia. 2010;51(10):2175-89
Riikonen RS. Favourable prognostic factors with infantile spasms. Eur J Paediatri neurol. 2010:14(1): 13-8.

Maguire MJ, et al. Prevalence of visual field loss following exposure to vigabatrin therapy: a systematic review. Epilepsia 2010:51(12):2423-31.
Kossoff EH. Infantile spasms. Neurologist. Mar 2010. 16(2): 69-75.

Hancock EC. Treatment of infantile spasms. Cochrane Database Syst Rev. 2008:(4): CD 001770.

JOURNAL ARTICLES
Mohamed BP, et al. Seizure outcome in infantile spasms- a retrospective study. Epilepsia. 2011: 52(4):746-52.

O'Callaghan FJ. et al. The effect of lead time to treatment and of age of onset as evidence from the United Kingdom Infantile Spasms trial. Epilepsia. Jul 2011. 52(7): 1359-64.

Yum MS. Surgical treatment for localization related infantile spasms. Clinical Neurology and Neurosurgery. Apr 2011. 113 (3):213-7.

Caraballo RH, et al. Infantile spasms without hypsarrythmia: a study of 16 cases. Seizure. Apr 2011. 20(3): 197-202.

Olson HE, et al. Rufinamide for the treatment of epileptic spasms. Epilepsy and Behavior. Feb 2011. 20(2):344-8.

Osborne, JP, et al. The underlying etiology of infantile spasms (West syndrome) from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. Oct 2010. 51(10):2168-74.

Hong AM, et al. Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants. Epilepsia 2010:51(8):1403-7.

Darke K, et al. Developmental and epilepsy outcomes at age 4 years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: a multi-centre randomised trial. Arch Dis Child. 2010:95(5): 382-6.

Elterman RD, et al. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol. 2010:25(11): 1340-7.

Yum MS, et al. Zonisamide in West syndrome: an open label study. Epileptic Disord. 2009:11(4):339-44.

Peltzer B, et al. Topiramate and adrenocorticotropic hormone (ACTH) as initial treatment for infantile spasms. J Child Neurol. 2009:24(4): 400-5.

Lux, AL, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicenter randomized trial. Lancet Neurol 2005; 4:714-7.

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.

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.

INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Epileptic Encephalopathy, Early Infantile, 1; EIEE1. Entry No: 308350. Last Edited:December 22, 2011. http://omim.org/entry/308350 Accessed on:February 1, 2012.

Glauser, TA. Infantile Spasm (West Syndrome) eMedicine. http://www.emedicine.com/neuro/topic171.htm Updated:January 26, 2012. Accessed on:February 1, 2012.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2012/02/06 00:00:00 GMT+0

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