Aniridia, cerebellar ataxia, and mental deficiency, also known as Gillespie syndrome, is an extremely rare inherited disorder that is characterized by the absence, in whole (aniridia) or in part (partial aniridia), of the colored portion (iris) of the eye; impaired coordination of voluntary movements due to underdevelopment (hypoplasia) of the brain's cerebellum (cerebellar ataxia); and mental retardation. The condition usually affects both eyes (bilateral) but a few cases have been reported in which only one eye is affected. Some individuals with this syndrome also exhibit a delay in the acquisition of skills requiring coordination of muscular and mental activity (psychomotor retardation). ACAMD is thought to be inherited as an autosomal recessive genetic trait and is extremely rare, with only 20 to 30 cases reported in the medical literature.
Aniridia-cerebellar ataxia-mental deficiency, also known as Gillespie syndrome, is an extremely rare inherited disorder that is characterized by malformations of the eye, neuromuscular abnormalities, developmental delays, and/or mental retardation. Some affected individuals may also exhibit additional physical abnormalities.
The eye abnormality most frequently associated with this disorder is the partial or complete absence of the colored portion (iris) of the eye, resulting in poor vision. Both eyes are usually affected (bilateral). The inner edge of the iris that normally surrounds the pupil (pupillary margin of iris) may be absent, as may be the circular band of muscle fibers in the iris that reduces the size of the pupil (sphincter pupillae) in response to light. In many cases, people with aniridia may also exhibit repeated, involuntary movements of the eye (nystagmus). In addition, during late childhood or early adolescence, the pressure of the fluid in the eye may become abnormally high (glaucoma) in some individuals with aniridia, potentially leading to progressive loss of vision.
Individuals with aniridia-cerebellar ataxia-mental deficiency may also have additional eye abnormalities, such as excessive widening (dilatation) of the pupils (mydriasis) and/or extreme sensitivity to light (photophobia). In addition, they may exhibit droopy eyelids (ptosis); inward deviation of one eye (esotropia), resulting in double vision (diplopia); and/or farsightedness (hypermetropia), causing blurred vision, eye strain, and/or difficulty in viewing close objects.
Aniridia-cerebellar ataxia-mental deficiency is also characterized by neuromuscular abnormalities, such as an impaired ability to coordinate voluntary movement due to incomplete development (hypoplasia) of the cerebellum (cerebellar ataxia). The cerebellum is the part of the brain that plays a role in maintaining balance and posture as well as coordinating voluntary movement. People with this disorder may walk unsteadily and have difficulty positioning the feet and turning (cerebellar gait); they may also speak slowly and haltingly, with pauses between each syllable (scanning speech). Affected individuals may also exhibit severely diminished muscle tone (hypotonia). The cerebellar ataxia does not seem to worsen over time in individuals with this disorder (non-progressive cerebellar ataxia); in fact, in some cases, the control of certain voluntary movements may improve with age.
People with this disorder may also exhibit developmental abnormalities, such as a delay in the acquisition of skills requiring the coordination of muscular and mental activity (psychomotor retardation). As a result, they may achieve certain developmental milestones (e.g., crawling, walking, speaking, etc.) later than normally expected. Mild to moderate mental retardation may also be present.
In rare cases, individuals with aniridia-cerebellar ataxia-mental deficiency may have additional physical abnormalities. For example, affected individuals have exhibited skeletal malformations, such as fusion of certain bones in the spinal column of the neck (cervical vertebrae), flat feet (pes planus), and/or feet with heels that are abnormally turned inward and soles that are flexed (equinovarus clubfeet). Other features have included heart abnormalities, such as a heart murmur, and/or abnormal narrowing of the opening between the heart’s right ventricle and the artery that supplies blood to the lung (pulmonary stenosis).
The disorder aniridia, cerebellar ataxia and mental deficiency is thought to be inherited as an autosomal recessive genetic trait, but researchers have not yet been able to establish the mode of inheritance conclusively. The genetics of the disorder are not well understood at this time.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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.
Aniridia, cerebellar ataxia and mental deficiency is an extremely rare inherited disorder that appears to affect females more than males, although the sample size is very low. Only about 20 or 30 cases have been reported in the medical literature. One report suggests that people with this syndrome make up about 2% of all patients with aniridia.
The diagnosis of aniridia, cerebellar ataxia and mental deficiency may be made at birth if the newborn (neonate) presents with partial absence of the iris in association with hypotonia. Although partial aniridia may be obvious at birth, the other symptoms may not become apparent until later in the child's development. Therefore, the disorder usually is not diagnosed until early childhood, based upon a thorough clinical evaluation, a detailed patient history, specialized laboratory tests, and advanced imaging techniques.
Examination of the eyes using a slit-lamp and an instrument that measures certain angles in the eye (gonioscope), and to reveal any remnants of iris tissue that may be present, help to establish and confirm a diagnosis of partial aniridia. If involuntary movements of the eye (nystagmus) occur in association with aniridia, the ophthalmologist will record eye movements to determine the exact type of nystagmus present.
Cerebellar ataxia due to underdevelopment of the cerebellum (cerebellar hypoplasia) may be confirmed by imaging techniques such as CT (computerized tomography) scanning and MRI (magnetic resonance imaging). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of different organs of the body.
The treatment of ACAMD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat diseases of the eye (ophthalmologists), specialists who assess and correct visual problems with corrective lenses (optometrists), physical therapists, and others may need to work together to ensure a comprehensive approach to treatment.
Early intervention is also important in ensuring that affected children with cerebellar ataxia, developmental delays, and mental retardation 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 also be of benefit for affected families. Other treatment is symptomatic and supportive.
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Kanski JJ, ed. Clinical Ophthalmology. 4th ed. Butterworth-Heinemann. Oxford, UK; 1999:240-42.
Kieslich M, Vanselow K, Wildhardt G, et al. [Present limitations of molecular biological diagnostics of Gillespie syndrome] Klin Peiatr. 2001;213:47-49. German with English abstract.
Dolfus H, Joanny-Flinois O, Doco-Fenzy M, et al. Gillespie syndrome phenotype with a t(X;11)9p22.32;p12) de novo translocation. Am J Ophthalmol. 1998;125:397-99.
Nelson J, Flaherty M, Grattan-Smith P. Gillespie syndrome: report of two further cases. Am J Med Genet. 1997;71:134-38.
Glaser T, Ton CC, Mueller R, et al. Absence of PAX gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation). Genomics. 1994;19:145-48.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Aniridia, Cerebellar Ataxia, and Mental Deficiency. Entry Number; 206700: Last Edit Date; 3/17/2004.
Bakri S. Simon JW. Aniridia in the Newborn. emedicine. Last Updated: June 16, 2005. 10pp.
Gnasia ER. Aniridia, cerebellar ataxia, and mental deficiency. Orphanet. December 2004. 1p.
Gillespie Syndrome. Aniridia Network. nd. 3pp.
Gillespie syndrome 2. Jablonski’s Syndromes Database. Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. nd. 2pp.
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