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Congenital Bilateral Perisylvian Syndrome

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.

Copyright 1996, 2001, 2003, 2012

NORD is very grateful to Phillip L. Pearl, MD, Division Chief, Child Neurology, Children's National Medical Center; Professor of Pediatrics and Neurology, The George Washington University School of Medicine, for assistance in the preparation of this report.

Synonyms of Congenital Bilateral Perisylvian Syndrome

Disorder Subdivisions

General Discussion

Congenital bilateral perisylvian syndrome (CBPS) is an extremely rare neurological disorder that may be apparent at birth (congenital), infancy, or later during childhood. It is characterized by partial paralysis of muscles on both sides (diplegia) of the face, tongue, jaws, and throat (pseudobulbar palsy); difficulties in speaking (dysarthria), chewing (mastication), and swallowing (dysphagia); and/or sudden episodes of uncontrolled electrical activity in the brain (epilepsy). In most cases, mild to severe intellectual disability is also present. Associated symptoms and findings are thought to be due to improper development of the outer surface of the brain (cerebral cortex) during embryonic growth (neuronal dysmigration). In most cases, the disorder appears to occur randomly for unknown reasons (sporadically).

Symptoms

CBPS is characterized by partial paralysis of the muscles on both sides of the face (facial diplegia), seizures, and intellectual disability.

In those with CBPS, impairment of certain nerves (cranial nerves) that emerge from the brain may result in sudden, involuntary spasms of facial muscles as well as partial paralysis of both sides (diplegia) of the face, jaws, tongue, and throat (pharynx). Impaired control of these muscles may cause difficulty chewing (mastication), swallowing (dysphagia), and/or pronouncing certain sounds and words (dysarthria). In some cases, affected individuals may be unable to speak.

Most individuals with CBPS also experience seizures or sudden recurrent episodes in which uncontrolled electrical discharges from nerve cells (neurons) of the outer region of the brain (cerebral cortex) cause involuntary muscle contractions, sensory disturbances, loss of consciousness, and/or other associated findings (epilepsy). Several different types of seizures may occur in the same affected individual. However, reports indicate that the epileptic seizures are most frequently generalized rather than partial in nature. (Epileptic seizures may be broadly categorized into generalized and partial seizures. Generalized seizures appear to arise over a wide area or both sides or hemispheres of the cerebral cortex, while partial seizures have an onset limited to a part of one hemisphere.)

In some cases, generalized seizures may be characterized by sudden breaks or momentary lapses of awareness or action; fluttering of the eyelids; twitching of facial muscles; and/or other findings (absence or petit mal seizures). In those with CBPS, the beginning and end of such seizure episodes may not be as distinct as often seen in absence seizures or they may be associated with loss of muscle tone or other atypical findings (i.e., atypical absence or petit mal seizures). Additional types of generalized seizures occur in some cases. Some affected individuals may have seizure episodes characterized by sustained muscle contraction or muscle jerks followed by sudden loss of muscle tone (atonic [astatic] seizures), potentially causing falls. In addition, some may have seizures characterized by an abrupt loss of consciousness, generalized stiffening of muscles, rhythmic contraction and relaxation of all muscle groups, and other findings (tonic-clonic or grand-mal seizures). In some cases, affected infants may first experience seizures characterized by sudden, brief, involuntary contractions of the neck, trunk, arms, and legs (infantile spasms or West Syndrome). (For more information on these seizure types, use "Epilepsy" or "West" as your search terms in the Rare Disease Database.)

Children with CBPS may also have delays in the development of certain physical, mental, and behavioral skills that are typically acquired at particular stages (developmental milestones), such as language and speech development and certain motor abilities. In addition, mild to severe intellectual disability is usually present.

Causes

The exact cause of CBPS is not completely understood. Associated symptoms and findings are believed to be due to improper development of the outer surface of the brain (cerebral cortex) during embryonic growth. The cerebral cortex, which is responsible for conscious movement and thought, normally consists of several deep folds (gyri) and grooves (sulci). However, in cases of CBPS, newly developed embryonic cells (neuroblasts) fail to migrate to their destined locations in the outer portion of the brain (neuronal dysmigration). As a result, the cerebral cortex does not develop the normal number of cellular layers, and the deep grooves (sulci) that normally develop on the sides (lateral) of both cerebral hemispheres (sylvian fissures or sulcus lateralis cerebri) may form improperly, resulting in an abnormally increased number of folds (gyri) that are unusually small (bilateral perisylvian polymicrogyria). In some cases, the groove separating the front (frontal) and side (parietal) portions (lobes) of the brain (fissure of Rolando or sulcus centralis cerebri) may also be malformed.

In most cases, CBPS appears to occur randomly for unknown reasons (sporadically) in the absence of a family history. However, a few families have been reported in which more than one member has been affected. In such cases, researchers suggest that the condition may potentially be due to an underlying genetic abnormality that may have autosomal recessive inheritance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Affected Populations

CBPS is an extremely rare neurological disorder that was first recognized as a distinct syndrome in the early 1990s. The disorder is usually apparent at birth (congenital) or early in life, based upon characteristic physical findings and specialized imaging tests. In affected individuals who exhibit infantile spasms (West Syndrome), onset of these sudden, involuntary contractions tends to occur within the first six months of life. Onset of other forms of epilepsy potentially associated with CBPS (e.g., atypical absence seizures, atonic-tonic seizures, and/or tonic-clonic seizures) may occur between two to 12 years of life. CBPS appears to affect males and females in equal numbers. Approximately 40 cases of CBPS have been reported in the medical literature.

Related Disorders

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

Pachygyria with mental retardation and seizures is a rare neurological disorder that is characterized by moderate intellectual disability; delays in the acquisition of skills requiring the coordination of physical and mental activities (psychomotor retardation); and/or sudden episodes of uncontrolled electrical activity in the brain (epilepsy). Several different types of epileptic seizures may occur in the same affected individual. Associated symptoms and findings are believed to result from abnormal development of the outer portion of the brain (cerebral cortex) during embryonic growth (neuronal dysmigration). In pachygyria with mental retardation and seizures, it is believed that there is a reduced number of folds in the cerebral cortex that are larger than normal (pachygria) or that the deep folds are abnormally numerous and small (polymicrogyria). In some cases, it is thought that the neuronal dysmigration may be due to an underlying genetic abnormality that may be transmitted as an autosomal recessive trait.

In double cortex syndrome, an abnormal band of brain tissue is present under the outer region of the brain (subcortical band heterotopia); as a result, it may appear as if the brain has a "double" cerebral cortex. Symptoms may vary from case to case, depending upon the extent of cerebral cortex malformation. Most affected individuals have various forms of epilepsy and mild to moderate intellectual disability. Some researchers believe that, in some cases, the abnormal development of the cerebral cortex during embryonic growth (neuronal dysmigration) may be due to an underlying genetic abnormality that may be transmitted as an autosomal dominant trait.

Lissencephaly is a rare brain malformation that may occur as an isolated condition or in association with certain underlying syndromes. The condition is characterized by incomplete development of the folds (gyri) of the cerebral cortex, causing the brain’s surface to appear unusually smooth (agyria). Affected infants may have an abnormally small head (microcephaly); seizures; severe or profound intellectual disability; growth retardation; and impaired motor abilities. If an underlying syndrome is present, there may be additional symptoms and physical findings, such as distinctive abnormalities of the skull and facial (craniofacial) region and/or other physical malformations. Lissencephaly may appear to occur randomly for unknown reasons (sporadically), be inherited, or occur in association with various underlying disorders. (For more information, choose "lissencephaly" as your search term in the Rare Disease Database.)

Neuronal migration disorders are a category of rare neurological disorders, including CBPS, pachygyria with mental retardation and seizures, double cortex syndrome, and lissencephaly, that result from improper development of the cerebral cortex. During normal embryonic growth, newly developed embryonic cells that will later become nerve cells (neuroblasts) migrate to the surface of the brain (neuronal migration), forming several cellular layers. If these embryonic cells fail to migrate to their destined locations (dysmigration), the cerebral cortex may not develop the normal number of cellular layers; as a result, there may be structural abnormalities of the brain's two cerebral hemispheres, such as improper development of the deep grooves (sulci) and folds (gyri) that normally form within the cerebral cortex. Neuronal migration disorders are often characterized by seizures and mild to severe intellectual disability. (For more information on these disorders, use "neuronal migration" or "neuronal dysmigration" as your search terms in the Rare Disease Database.)

Standard Therapies

CBPS may be diagnosed at birth or early in life, based upon a thorough clinical evaluation, a detailed patient history, and a complete neurological evaluation including advanced imaging techniques such as electroencephalography (EEG), computerized tomography (CT) scanning, or magnetic resonance imaging (MRI).

During an EEG, the brain's electrical impulses are recorded; such studies may reveal brain wave patterns that are characteristic of certain types of epilepsy. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the brain.

CT and MRI images may confirm malformations of certain areas of the cerebral cortex (perisylvian and/or perirolandic malformations) and abnormalities of the brain's deep folds and grooves. In addition, analysis of speech abnormalities due to impaired muscle control (dysarthria) may reveal characteristic patterns among individuals with CBPS, such as difficulty with certain vowels or noise ranges.

The treatment of CBPS 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, physical therapists, and others may need to systematically and comprehensively plan an affected child's treatment.

Treatment with anticonvulsant drugs may help prevent, reduce, or control various types of epilepsy associated with CBPS. In affected infants who exhibit sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms in the first six months of life (infantile spasms or West Syndrome), treatment with adrenocorticotropic hormone (ACTH or corticotropin) has resolved the seizures in some cases. In cases when drug therapy is ineffective in preventing or controlling seizures (intractable epilepsy), surgical removal of tissue in certain areas of the brain (focal corticectomy) or surgical division (callosotomy) of the fibers joining the two cerebral hemispheres (corpus callosum) may result in seizure improvement.

Early intervention is important in ensuring that children with CBPS reach their potential. Special services that may be beneficial to affected children may include physical therapy, special remedial education, speech therapy, and other medical, social, and/or vocational services.

Genetic counseling will be of benefit for affected children and their families. Other treatment is symptomatic and supportive.

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 NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (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

Organizations related to Congenital Bilateral Perisylvian Syndrome

[Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., epilepsy or mental retardation).]

References

JOURNAL ARTICLES
Tagawa T, et al. Nonconvulsive status epilepticus in a child with congenital bilateral perisylvian syndrome. Pediatr Neurol. 1999;21:579-82.

Olsen PM, et al. Congenital bilateral perisylvian syndrome. Ugeskr Laeger. 1998;160:4307-309.

Baykan-Kurt B, et al. A clinically recognizable neuronal migration disorder: congenital bilateral perisylvian syndrome. Case report with long-term clinical and EEG follow-up. Seizure. 1997;6:487-93.

Hattori H, et al. Congenital bilateral perisylvian syndrome: first report in a Japanese patient. Jpn J Hum Genet. 1996;41:189-92.

Kuzniecky R, et al. The epileptic spectrum in the congenital bilateral perisylvian syndrome. CBPS multicenter collaborative study. Neurology. 1994;44:379-85.

Kuzniecky R, et al. The congenital bilateral perisylvian syndrome: imaging findings in a multicenter study. CBPS study group. AJNR Am J Neuroradiol. 1994;15:139-44.

Kuzniecky R, et al. Infantile spasms: an early epileptic manifestation in some patients with the congenital bilateral perisylvian syndrome. J Child Neurol. 1994;9:420-23.

Kim HI, et al. Congenital bilateral perisylvian syndrome: analysis of the first four reported Korean patients. J Korean Med Sci. 1994;9:335-40.

Kuzniecky R. Familial diffuse cortical dysplasia. Arch Neurol. 1994;51:307-10.

Kuzniecky R, et al. Congenital bilateral perisylvian syndrome: study of 31 patients. The CBPS multicenter collaborative study. Lancet. 1993;341:608-12.

Palmini A, et al. Stages and patterns of centrifugal arrest of diffuse neuronal migration disorders. Dev Med Child Neurol. 1993;35:331-39.

Shevell MI, et al. Developmental bilateral perisylvian dysplasia. Pediatr Neurol. 1992; 8:299-302.

Report last updated: 2012/10/12 00:00:00 GMT+0