SNP Shot: Genomic Insights

Gillespie syndrome is a rare genetic condition characterized by a combination of features: unusual eye development, low muscle tone present from birth (congenital hypotonia), difficulty with balance and coordination (ataxia), and mild to moderate intellectual disability.

A key feature of Gillespie syndrome is the underdevelopment (hypoplasia) of the iris, the colored part of the eye. Typically, individuals with Gillespie syndrome are missing a portion of the iris (partial aniridia) in both eyes. The remaining iris often displays a distinctive "scalloped" or uneven edge along the pupil. The pupils are abnormally large (dilated) and do not constrict in response to light. These pupil abnormalities stem from issues with the development or function of the sphincter pupillae muscles, which control pupil contraction. These eye problems can lead to blurry vision (reduced visual acuity), sensitivity to light (photophobia), and involuntary rapid eye movements (nystagmus).

The balance and coordination problems seen in Gillespie syndrome are related to the underdevelopment (hypoplasia) of the cerebellum, the brain region responsible for coordinating movement. Cerebellar hypoplasia can cause hypotonia and delays in motor skill development, such as learning to walk. Additionally, difficulties controlling mouth muscles can contribute to delayed speech development. Coordination difficulties typically become apparent in early childhood as the individual attempts to master these skills. Individuals with Gillespie syndrome often experience persistent gait instability and speech difficulties throughout their lives.

Other possible features of Gillespie syndrome include vertebral (spinal bone) abnormalities and heart malformations.

Inheritance:

Gillespie syndrome can follow an autosomal recessive inheritance pattern. In these cases, a mutation must be present in both copies of the responsible gene in each cell. Both parents of an individual with autosomal recessive Gillespie syndrome carry one copy of the mutated gene, but usually do not exhibit any signs or symptoms of the condition themselves. In other cases, Gillespie syndrome follows an autosomal dominant pattern of inheritance, requiring only one copy of the mutated gene in each cell to cause the disorder. Some individuals inherit the altered gene from a parent who also has the condition. Other cases result from new (de novo) mutations in the gene, occurring in individuals with no family history of Gillespie syndrome. It is believed that autosomal dominant Gillespie syndrome cases occur through a dominant-negative effect, where the altered protein produced from the mutated gene interferes with the function of the normal protein produced from the healthy copy of the gene.