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Oculocerebrocutaneous Syndrome

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Copyright 1994, 2000, 2003

Synonyms of Oculocerebrocutaneous Syndrome

Disorder Subdivisions

General Discussion

Oculocerebrocutaneous (OCC) syndrome, a rare genetic disorder, is apparent at birth (congenital). The disorder is characterized primarily by eye (ocular), brain (e.g., cerebral), and skin (cutaneous) malformations. For example, many affected infants have semisolid or fluid-filled swellings (cysts) within the cavities of the skull (orbits) that accommodate the eyeballs and associated structures. In most cases, the eye on the affected side or sides is also abnormally small (microphthalmos). Brain abnormalities associated with OCC syndrome may include malformations of the ventricular system in the middle of the brain, multiple fluid-filled spaces within the outer region of the cerebral hemispheres (cerebral cortex), and absence of the band of nerve fibers that joins the brain's hemispheres (agenesis of the corpus callosum). Affected infants and children may also have mental retardation and episodes of uncontrolled electrical activity in the brain (seizures). In addition, OCC syndrome is characterized by underdevelopment or absence of skin in certain localized regions (focal dermal hypoplasia or aplasia) and most have protruding, flesh-colored or brownish outgrowths of skin (cutaneous tags) within certain facial areas, including around the eyelids, on the cheeks, or near the ears. In all individuals with OCC syndrome, the disorder appears to occur randomly for unknown reasons (isolated, with no family history of similar disorders).

Symptoms

Oculocerebrocutaneous (OCC) syndrome is characterized by distinctive eye (ocular), brain (e.g., cerebral), and skin (cutaneous) malformations. Most infants with the disorder have fluid-filled or semisolid swellings (cysts) within the cavities of the skull (orbits) that accommodate the eyeballs. The eye on the affected side or sides is characteristically small (microphthalmos) or, more rarely, may be absent (anophthalmia). In some cases, the orbital cysts may contain benign (noncancerous), tumor-like nodules (hamartomas) consisting of ocular tissue. Affected infants may have additional ocular abnormalities, such as absence or defects (notches) of tissue (colobomas) of the upper eyelids, the lower eyelids, or the colored part of the eye(s) (irises) or abnormal persistence of the embryonic blood vessel (the hyaloid artery system) that supplies certain regions of the eyes (persistent fetal vasculature). (The hyaloid artery usually disappears during the ninth month of fetal development.)

Infants with OCC syndrome may also have skeletal abnormalities. These may include underdevelopment (hypoplasia) of the orbits or other bones of the skull (e.g., zygomas); malformation of certain ribs or of the bones of the spinal column (vertebrae); and/or abnormal curvature of the spine (scoliosis).

OCC syndrome is also characterized by abnormalities of the brain. These malformations include the presence of abnormal, fluid-filled spaces in the outer region of the cerebral hemispheres (cerebral cortex) and absence of the band of nerve fibers that joins the brain's hemispheres (agenesis of the corpus callosum). Many affected infants also have mental retardation, substantial delay in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), and episodes of uncontrolled electrical activity in the brain (seizures). Less commonly, infants with OCC syndrome may also have obstructive hydrocephalus, a condition in which there is obstructed flow of the fluid surrounding the brain and spinal cord (cerebrospinal fluid [CSF]), resulting in increasing fluid pressure in the brain. Associated symptoms and findings may include abnormal enlargement of the cavities (ventricles) of the brain, and rapid enlargement of the head. In rare cases, infants with OCC syndrome may have protrusion of a portion of the brain and its surrounding membranes (meninges) through a defect in the back of the skull (occipital meningoencephalocele).

OCC syndrome also has distinctive skin (cutaneous) abnormalities. Most infants with the disorder have multiple localized areas in which the skin is underdeveloped (hypoplastic), absent (aplastic), or characterized by "punched-out" defects. In some cases, involved areas appear as abnormal depressions in the skin. Although these lesions primarily affect the head, face, and trunk, they may occur anywhere on the body. Many affected infants also have protruding, brownish or flesh-colored outgrowths of skin (skin or cutaneous tags). Such cutaneous outgrowths usually appear around the eyes (periorbital). However, they may occur in other facial regions, such as the cheeks or near the ears, or, more rarely, in other bodily areas.

In some infants with OCC syndrome, the various cutaneous, ocular, orbital, or other malformations may involve one side of the body (unilateral). In those with unilateral involvement, the left side has been affected about twice as often as the right. As a result, the face appears different on one side from the other (facial asymmetry). Less commonly, due to the presence of certain skeletal abnormalities, such as those mentioned above, one side of the body may appear different from the other (generalized body asymmetry).

In rare cases, infants with OCC syndrome may have other signs, including incomplete closure of the roof of the mouth (cleft palate) or other physical features.

Causes

In all reported individuals with oculocerebrocutaneous (OCC) syndrome, there is no family history of the disorder. Therefore, geneticists suggest that OCC syndrome is caused by a new genetic event (a mutation) that appears to occur randomly for unknown reasons (isolated).

In addition, in a few reported cases, affected individuals have had relatives with conditions distantly similar to OCC syndrome. For example, the mother of one affected individual had defects of ocular tissue affecting both eyes (bilateral colobomas), and a cousin of another had an ocular cyst. According to some researchers, such findings suggest that OCC syndrome might be transmittable as an autosomal dominant trait with variable expressivity.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50%for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Oculocerebrocutaneous (OCC) syndrome has been reported more frequently in males than in females. Since the disorder was originally described in 1981 (JW Delleman), approximately 30 cases have been reported in the medical literature.

Related Disorders

Symptoms of the following disorders may be similar to those of oculocerebrocutaneous (OCC) syndrome. Comparisons may be useful for a differential diagnosis:

Microphthalmia with linear skin defects syndrome (also called microphthalmia, dermal aplasia, and sclerocornea, MIDAS syndrome) is a rare genetic disorder that appears to be caused by an alteration on the X chromosome. The disorder is characterized by eye (ocular) defects, including abnormally small size of the eyes (microphthalmia); fluid-filled swellings (cysts) within the cavities of the skull that accommodate the eyeballs (orbits); and clouding of the front, usually transparent surface of the eyes (corneal opacities). These ocular defects typically occur in association with underdevelopment or absence of skin in "streak-like" (linear) patterns, primarily affecting the head and neck region. Some affected females (or infants with chromosomal anomalies affecting the X chromosome and another chromosome) may have additional abnormalities, including diaphragmatic hernia, respiratory distress in the newborn period, genital malformations, absence of the band of nerve fibers that joins the two hemispheres of the brain (agenesis of the septum pellucidum), episodes of uncontrolled electrical activity in the brain (seizures), or mental retardation.

Focal dermal hypoplasia (also called Gorlin syndrome or Gorlin-Goltz syndrome) is a rare genetic X-linked disorder. The condition is characterized by distinctive abnormalities of the skin, the fingers and toes (digits), the eyes, and other bodily regions. Primary cutaneous abnormalities include underdevelopment of localized areas of skin (focal dermal hypoplasia) with protrusion of fat (herniation); red streaking of the skin; and multiple benign (noncancerous) tumors (papillomas) of the skin or mucous membranes (including the esophagus and the larynx). Most affected females also have ocular defects, such as small eyes (microphthalmia); absence or defects of ocular tissues (colobomas of the iris or the choroid); or abnormal malalignment of one eye in relation to the other (strabismus, usually turned in or esotropia). Limb malformations may include webbing or fusion (syndactyly) of certain fingers or toes; permanent flexion of one or more digits (camptodactyly); additional fingers or toes (polydactyly); or absence of certain digits (usually in the middle of the hand). Also present are skeletal abnormalities, such as an unusually small, rounded skull; malformations of bones in the spinal column (vertebrae); unusual streaks (striations) in the long bones or abnormal curvature of the spine. Many affected individuals also have abnormal eruption, irregular spacing, defective enamal, or absence of some teeth (hypodontia); overgrowth (hypertrophy) of the gums; an abnormal vertical notch in the upper lip (cleft lip); incomplete closure of the roof of the mouth (cleft palate); or other physical abnormalities. Most individuals with the disorder have mental retardation. (For further information on this disorder, choose "focal dermal hypoplasia" as your search term in the Rare Disease Database.)

Encephalocraniocutaneous lipomatosis (ECCL), also called Proteus syndrome, is a rare genetic disorder that is typically characterized by skin abnormalities and ocular defects involving one side of the body (unilateral), episodes of uncontrolled electrical activity in the brain (seizures), and mild to severe mental retardation. Affected individuals may have multiple benign fatty tumors (lipomas) and other benign tumor-like lesions (hamartomas), involving skin of the forehead, cheeks, neck, eyelids, or the surface of the eye (epibulbar dermoids). Additional findings include fluid-filled spaces in the brain (porencephalic cysts) and lipomas of the protective membranes surrounding the brain and spinal cord (i.e., leptomeninges). Affected individuals may have a large head (macrocephaly); hydrocephalus; bony overgrowth of the skull, face and mandible (hyperostosis); localized loss of scalp hair (alopecia); or protruding outgrowths of skin (skin tags) that may involve the eyelids, the nose, or other regions. Some investigators suggest that ECCL may be a localized form of the rare genetic disorder known as Proteus syndrome. (For more information, choose "Proteus" as your search term in the Rare Disease Database.) To date, all individuals with ECCL are the only individuals in their families with the disorder (isolated).

Goldenhar syndrome, a term used synonymously with "oculo-auriculo-vertebral (OAV) spectrum," is a rare genetic disorder apparent at birth (congenital). The disorder is characterized by a wide spectrum of signs and physical features that vary greatly in extent and severity from case to case. However, the abnormalities tend to involve the cheekbones, jaws, mouth, ears, eyes, and bones of the spinal column (vertebrae). Although the malformations usually affect one side of the body (unilateral), some affected individuals have such abnormalities on both sides (bilateral) in which one side (usually the left) is more affected than the other. Due to these malformations, the face may appear smaller on one side (hemifacial microsomia). If both sides are affected (bilateral), the face may appear smaller on one side than the other (facial asymmetry). Craniofacial abnormalities include underdevelopment of the cheekbones (malar hypoplasia), bones of the upper and lower jaws, and bones forming a portion of the lower skull (temporal hypoplasia); incomplete development of certain muscles of the face; an abnormally wide mouth (macrostomia); incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip); and/or abnormalities of the teeth. Malformation (microtia) or absence (anotia) of the outer ears (auricles or pinnae) also occurs; narrow, blind ending, or absent external ear canals (atresia); abnormal outgrowths of skin and cartilage on or in front of the ears (preauricular tags); or abnormalities affecting the middle or inner ears, resulting in hearing impairment (either conductive or sensorineural hearing loss). Eye abnormalities may include the formation of solid benign tumors on the surface of the eyeball(s) (epibulbar dermoids and lipodermoids), partial absence of tissue (coloboma) from the upper eyelids, abnormally small eye(s) (microphthalmia), narrowing of the openings (palpebral fissures) between the upper and lower eyelids (blepharophimosis), or other ocular abnormalities. In some individuals, additional physical malformations and/or mild mental retardation may occur. Goldenhar syndrome is usually an isolated event with no family history. A few reports imply is a positive family history, suggesting autosomal dominant or autosomal recessive inheritance. In addition, some investigators have suggested that the disorder may be caused by the combined interaction of a few genes (oligogenic inheritance). (For further information on this disorder, choose "Goldenhar" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Oculocerebrocutaneous (OCC) syndrome may be diagnosed at or shortly after birth based upon a thorough clinical evaluation, identification of characteristic physical findings, and specialized imaging techniques. Some investigators have suggested that minimal diagnostic criteria for OCC syndrome must include the presence of orbital cysts or small eyes (microphthalmia); fluid-filled spaces in the outer region of the brain or obstructed flow of cerebrospinal fluid in the brain, causing increased fluid pressure (hydrocephalus); and localized (focal) skin abnormalities.

Specialized tests detect and/or characterize certain abnormalities associated with the disorder, including ocular defects, cerebral malformations, and seizure activity. These may include advanced imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI); or electroencephalography (EEG).

Treatment
The management of oculocerebrocutaneous (OCC) syndrome is directed toward the specific signs apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; surgeons; physicians who specialize in disorders of the skin (dermatologists); physicians who diagnose and treat neurological disorders (neurologists and neurosurgeons); eye specialists (ophthalmologists); and/or others.

Specific therapies for OCC syndrome are symptomatic and supportive. Intervention may include drainage of orbital cysts; surgical removal (excision) of orbital cysts, hamartomas, or skin tags; or surgical repair of certain abnormalities, such as colobomas of the lids or the cleft palate. The specific surgical interventions will depend on the severity of the anatomical abnormalities, their associated signs, and other factors.

Treatment may include medications to prevent, reduce, or control seizures (anticonvulsant drugs). Those with hydrocephalus may have a specialized device (shunt) surgically implanted to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed.

Genetic counseling may benefit the families of affected individuals. Other treatment for OCC syndrome 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.

Oculocerebrocutaneous Syndrome Resources

Organizations:

References

TEXTBOOKS
Buyse ML, ed. Birth Defects Encyclopedia. Blackwell Scientific Publications. 1990: 1274.

JOURNAL ARTICLES
Wilson RD, et al. Oculocerebrocutaneous Syndrome. Am J Ophthalmol. 1985;99:142-48.

Hoo JJ, et al. Oculocerebrocutaneous Syndrome. Am J Med Genet. 1991;40:290-93.

Leichtoman, AJMG 1994; McCandless AJMG 1998; and Moog, Genet Counsel. 1996.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number: 164180; Last Edit Date: 7/28/98.

Report last updated: 2008/04/21 00:00:00 GMT+0