NORD gratefully acknowledges Prof. Ute Moog, MD, PhD, Institute of Human Genetics, University of Heidelberg, for assistance in the preparation of this report.
Oculocerebrocutaneous (OCC) syndrome (OMIM 164180), 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 patients, the eye on the affected side or sides is also abnormally small (microphthalmos). Brain abnormalities associated with OCC syndrome may include enlargement of the ventricular system, multiple fluid-filled spaces within and malformations of the outer region of the cerebral hemispheres (cerebral cortex), absence of the band of nerve fibers that joins the brain's hemispheres (agenesis of the corpus callosum), and a typical malformation of mid- and hindbrain. Affected infants and children often have intellectual disability 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 known so far, the disorder occurs sporadically (with no family history of similar disorders).
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). 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 malformations of the cerebral hemispheres (cerebral cortex), mainly polymicrogyria or periventricular heterotopia; abnormal, fluid-filled spaces in the outer region of the cerebral cortex; absence of the band of nerve fibers that joins the brain’s hemispheres (agenesis of the corpus callosum); and a very characteristic malformation of the mid- and hindbrain with a giant tectum and missing or hypoplastic vermis of the cerebellum. The ventricles (fluid filled cavities) in the brain may be enlarged and obstructive hydrocephalus may occur, 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 leading to rapid enlargement of the head and other symptoms. Many affected infants have intellectual disability, substantial delay in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor impairment), and episodes of uncontrolled electrical activity in the brain (seizures). 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 more 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).
Rarely, infants with OCC syndrome may have other signs, including undescended testes, incomplete closure of the roof of the mouth (cleft palate), clefts involving larger parts of the face or other physical features.
In all reported individuals with OCC syndrome, there is no family history of the disorder. Therefore, geneticists suggest that OCC syndrome is caused by a genetic change (a mutation) that appears to be present in part of the cells of the body only (somatic mosaicism) and is thought to be the consequence of a randomly occurring, new event in one of the cells present at a very early embryonic stage.
A few affected individuals have had relatives with conditions distantly similar but probably unrelated 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.
The exact cause of OCC is still unknown and difficult to determine.
OCC syndrome has been reported more frequently in males than in females; however, the prevalence is unknown. Since the disorder was originally described in 1981 (JW Delleman & JWE Oorthuys), approximately 40 patients have been reported in the medical literature.
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 characteristic findings in at least two of the three systems typically involved (eye, skin, brain).
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).
The management of 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.
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Moog U, Dobyns WB. An update on oculocerebrocutaneous (Delleman-Oorthuys) syndrome. Am J Med Genet C Semin Med Genet. 2018 Dec;178(4):414-422.
Oculocerebrocutaneous Syndrome. Genetic and Rare Diseases Information Center (GARD). Last update 6/15/2015. https://rarediseases.info.nih.gov/gard/106/oculocerebrocutaneous-syndrome/resources/1 Accessed August 12, 2019.
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number: 164180; Last Edit Date: 02/19/2015. http://www.omim.org/entry/164180 Accessed August 12, 2019.
Moog,Ute. Oculocerebrocutaneous syndrome. Orphanet. August 2019; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1647 Accessed August 12, 2019.
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