Oculocerebral Syndrome with Hypopigmentation is an extremely rare inherited disorder characterized by the lack of normal color (hypopigmentation) of the skin and hair and abnormalities of the central nervous system that affect the eyes and certain parts of the brain (oculocerebral). Physical findings at birth include unusually light skin color and silvery-gray hair. Abnormal findings associated with the central nervous system may include abnormal smallness of one or both eyes (microphthalmia); clouding (opacities) of the front, clear portion of the eye through which light passes (cornea); and/or rapid, involuntary eye movements (nystagmus). Additional symptoms that may develop during infancy include involuntary muscle contractions, associated loss of muscle function (spastic paraplegia), developmental delays, and/or mental retardation. Oculocerebral Syndrome with Hypopigmentation is believed to be inherited as an autosomal recessive genetic trait.
Oculocerebral Syndrome with Hypopigmentation, also known as Cross Syndrome, is an extremely rare inherited disorder that may be apparent at birth (congenital) or during early infancy. The first visible signs of the disorder are decreased color (hypopigmentation) or total lack of color (depigmentation) of the skin and hair. The skin is usually very light and may be extremely sensitive to exposure to the sun. In most cases, the hair is often silvery or silvery-gray in color at birth. In addition, infants with Oculocerebral Syndrome with Hypopigmentation may be abnormally sensitive to light (photosensitivity).
Later during infancy, affected infants may begin to exhibit more serious abnormalities. By three months of age, an infant with Oculocerebral Syndrome with Hypopigmentation may exhibit symptoms associated with abnormalities of the central nervous system (i.e., affecting parts of the brain and the eyes). These symptoms may include slow involuntary purposeless movements of various muscles, especially those in the hands (athetoid movements); impaired ability to coordinate voluntary movements (ataxia); movement of the head beyond the normal range of motion (hyperextension), and/or increased rigidity in some muscles causing stiffness and limitation of movement. In more severe cases, children may experience lack of voluntary movements of the arms and legs (spastic tetraplegia). Other neurological symptoms may include exaggerated reflexes and/or fixation of several joints in a permanently flexed position (joint contractures). The legs, arms, shoulders, and hips are the sites that are most often involved. Affected individuals may also have a high-pitched cry or make constant sucking sounds.
Infants with Oculocerebral Syndrome with Hypopigmentation may also have abnormalities of the eyes including abnormal smallness of one or both eyes (microphthalmia). In some cases, the front clear portion of the eyes through which light passes (corneas) may also be unusually small (microcornea). Affected infants may also exhibit abnormal clouding (opacity) of the corneas; rapid side-to-side involuntary eye movements (horizontal nystagmus); an outward turning of the eyelids, exposing the delicate membranes that line the inside of the eyelids (ectropion palpebral conjunctivae); loss of transparency (opacity) of the lenses of the eyes (cataracts); and/or wasting away (atrophy) of the iris and/or the optic nerve (optic atrophy). Such eye abnormalities may result in varying degrees of visual impairment or, in some cases, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.
Children with Oculocerebral Syndrome with Hypopigmentation may also exhibit mental retardation, abnormally slow physical development (growth retardation), a delay in reaching developmental milestones (e.g., holding up their heads, sitting, walking, etc.), and/or a delay in the acquisition of skills requiring the coordination of muscular and mental activity (psychomotor retardation).
Between the ages of six months to three years, when the baby teeth emerge from the gums, most infants with this disorder may develop abnormally large gums (gingival fibromatosis). The overgrown gums may be pink and leathery and have small pebble-like bumps on the surface. In rare cases, the gums may completely cover the teeth and protrude from the mouth. If not corrected, enlargement of the gums may cause speech problems, or in severe cases, may interfere with breathing and swallowing.
Other findings in children with Oculocerebral Syndrome with Hypopigmentation may include an abnormally long appearance to the head (dolichocephaly), a highly-arched roof of the mouth (palate), widely spaced teeth, and/or underdevelopment of a muscle (diaphragm) that is necessary for proper breathing (oligophrenia). Oligophrenia may cause respiratory difficulties. In one case reported in the medical literature, urinary tract abnormalities were present.
Oculocerebral Syndrome with Hypopigmentation is believed to be inherited as an autosomal recessive genetic trait. 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.
Parents of several individuals with the disorder have been closely related by blood (consanguineous). In these cases, there is a higher than normal chance that both parents carry, and consequently may pass on, the genes necessary for development of the disorder.
Oculocerebral Syndrome with Hypopigmentation is an extremely rare disorder that affects males and females in equal numbers. Fewer than 15 cases have been reported in the medical literature. Most of these observed cases occurred within families.
Abnormally small eyes and lack of skin and hair color are usually apparent at birth (congenital). Neurological abnormalities (e.g., athetoid movements, ataxia, etc.) may become apparent by three months of age. Some affected infants exhibit abnormally enlarged gums (gingival fibromatosis) when the first teeth emerge from the gums (at age six months to three years). Other symptoms (e.g., developmental delays, mental retardation, etc.) may become apparent later during infancy or childhood.
The diagnosis of Oculocerebral Syndrome with Hypopigmentation may be confirmed based upon a thorough clinical evaluation and detailed patient history, characteristic physical findings, specialized laboratory tests, imaging techniques, and/or genetic testing. Oculocerebral Syndrome with Hypopigmentation may be suspected in infants with characteristic neurological and ocular abnormalities occurring in association with the presence of abnormally light skin and silvery-gray hair.
Abnormal lack of skin color (cutaneous hypopigmentation) and abnormally small eye(s) are usually obvious at birth or in early infancy. Ultrasonography may be used to confirm a diagnosis of microphthalmia. Ultrasonography, a testing method that creates an image of internal structures by measuring the reflection of sound waves, may demonstrate that the length from the front to the back of the eye (anteroposterior axis) is smaller than normal (microphthalmia). Horizontal side-to-side eye movements (nystagmus) and outward turning of the eyelids (ectropion palpebral conjunctivae) may also be observed at birth. Enlarged gums (gingival fibromatosis) may develop when the first teeth emerge from the gums (usually around six months to three years of age). Neurological abnormalities, such as athetoid movements and ataxia, may become apparent around three months of age. Other symptoms (e.g., developmental delays, mental retardation, etc.) may not become apparent until late infancy or childhood.
Internal abnormalities such as an underdeveloped diaphragm (oligophrenia) may be detected through a combination of observation and internal imaging techniques, such as computerized tomography (CT) scanning. CT scanning is an imaging technique in which a computer and x-rays are used to create a film showing cross-sectional images of certain organs.
The treatment of Oculocerebral Syndrome with Hypopigmentation is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dentists, physicians who specialize in disorders of the eyes (ophthamologists), physicians who specialize in skin disorders (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Specific therapies for the treatment of Oculocerebral Syndrome with Hypopigmentation are symptomatic and supportive. Due to lack of normal skin color, an affected child's skin may be highly sensitive to sun exposure; therefore, sunscreen, hats, and long sleeves may be recommended to avoid sunburn. Wearing sunglasses and other preventative measures may also be recommended to protect affected individuals from the sun.
Corrective glasses or contact lenses may be used to help improve vision. In some cases, eye surgery may be performed.
The size of the gums may be reduced with surgery. However, the enlargement may recur as more teeth emerge and/or when secondary teeth grow in, requiring subsequent surgery.
Early intervention is important to ensure that affected children with Oculocerebral Syndrome with Hypopigmentation reach their potential. Special services that may be beneficial to affected children may include special remedial education and other medical, social, and/or vocational services.
Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.
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