Gillespie syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 9, 2017
StartDiseasesGillespie syndrome

Gillespie syndrome is a disorder that causes eye deformities, developmental delays, and muscle coordination issues. It is named after American ophthalmologist Fredrick Gillespie, who discovered the disorder in 1965. Another name for Gillespie syndrome is Aniridia-cerebellar ataxia-mental deficiency or ACAMD.


Definition & Facts

Gillespie syndrome is the result of a gene mutation that contributes to the way an embryo develops in the womb, disrupting normal development of the eyes and the brain. One important trait of the disorder is aniridia, a partial or complete absence of the iris in one or both eyes. Because the iris (colored part of the eye) is not fully developed, the pupils are large and sensitive to light.

Another factor is the failure of the cerebellum to completely develop, leading to poor motor coordination, balance problems, and intellectual disability. All patients with Gillespie syndrome have aniridia, but only 2 percent of individuals who have aniridia also have Gillespie syndrome. Researchers believe the disorder is likely to be inherited, but it's extremely rare. Less than 30 cases have been reported in medical literature.

Symptoms & Complaints

About 90 percent of Gillespie syndrome patients have all three of these traits: an underdeveloped iris, cognitive impairment, and lack of coordination.

Children with Gillespie syndrome have round pupils, but the edges of the iris are scalloped, with strands of the iris extending into the front surface of the lens. Gillespie syndrome can also affect the cornea, optic nerve, and retina.

Without a full iris, vision is blurred, eyes are sensitive to the light, and patients experience involuntary eye movements. 50 percent or more patients experience blurred vision and light sensitivity. There's also an increased risk of glaucoma, scarring, and cataracts.

Another trait is the underdevelopment of the cerebellum, the area of the brain that receives information from the spinal cord and sensory systems, and in turn regulates motor movements. Individuals with this condition have weak muscle tone and have trouble walking. There have also been documented cases of delay in developmental skills like crawling, walking, and mild to moderate intellectual disabilities.


The cause of Gillespie syndrome is not known, although it is believed to be inherited. In a small number of individuals it is thought to be caused by a gene mutation which can be either dominant or recessive. The gene, called PAX6, lacks a protein that normally would bind to DNA and regulate the way other genes function. This disrupts the way an embryo develops, especially during the formation of the brain and eyes.

It is possible for both parents to carry the mutated gene without showing signs of the disorder. With each pregnancy shared by the same parents there's a 25 percent risk that the child will inherit one of these genes from each parent, giving the child the disease. In 50 percent of cases, the child may inherit only one mutated gene from one parent and will carry the gene, but still remain healthy. In another 25 percent of cases the child will not inherit the mutated gene and will still be healthy.

Diagnosis & Tests

There is no specific test for Gillespie syndrome, but it is important to have an infant tested by an ophthalmologist if an eye abnormality is suspected. Parents may notice that the child's pupils are large and dilated and that they are sensitive to light. This can be recognized within the first four weeks after birth. The ophthalmologist will likely test for aniridia, and determine if it is mild or severe.

Other vision problems can be diagnosed during infancy. However, even with a diagnosis of aniridia, it is still too early for Gillespie syndrome to be detected; not all children diagnosed with aniridia will have Gillespie syndrome.

The developmental and balance issues that accompany this disorder still haven't had a chance to manifest. As the child grows, if lack of coordination and cognitive impairment are suspected, additional testing should be done.

A full diagnosis can be made as early as 18 months to around age 3. Underdevelopment of the brain can be confirmed by imaging techniques, and the doctor may order a computed tomography (CT) scans or magnetic resonance imaging (MRI) scans of the brain. In some cases imaging will determine that the cerebrum and cerebellum are smaller than they should be, but this is not always a common characteristic of the disorder. 

Treatment & Therapy

Treatment for Gillespie syndrome is based on the specific symptoms and needs of the individual. Generally a group of specialists are required to coordinate an approach for care, including pediatricians, ophthalmologists, optometrists, physical therapists and others. Experts stress the importance of early intervention to ensure that children with visual problems, mental retardation, developmental delays, and coordination problems reach their full potential as adults.

Children with this disorder need training and stimulation to develop motor skills. Some may need eyeglasses. Others may benefit from the assistance of equipment like walkers or wheelchairs. Services that can be of assistance to affected children may include speech therapy, physical therapy, special education, and various social and vocational services. 

Prevention & Prophylaxis

There are no specific measures to take to prevent Gillespie syndrome, other than researching family history for any previous appearance of the disorder. Genetic counseling is often helpful to determine which risk factors are present and can be passed on to children. This is voluntary and can be done either before or during pregnancy, so that parents can make informed decisions.

One type of genetic test called carrier testing is used to identify people who carry one copy of a gene mutation. If it is present in both parents, it causes a genetic disorder. There is a blood test to identify the PAX6 gene. Arrangements can be made through a health care provider or genetic counselor. Since there is no cure for Gillespie syndrome, the best solution is to have the disorder diagnosed as early as possible, and manage symptoms with the help of health care professionals.