SNP Shot: Genomic Insights

Congenital fibrosis of the extraocular muscles (CFEOM) is a neurological condition affecting the muscles surrounding the eyes, known as extraocular muscles. These muscles are responsible for controlling eye movement and gaze direction. In individuals with CFEOM, the ability to control these muscles is impaired, resulting in abnormal eye movements. Most commonly, individuals experience difficulty looking upwards, and their side-to-side eye movements may also be restricted. Misalignment of the eyes (strabismus) is also common. To follow moving objects, individuals with CFEOM often turn their head instead of moving their eyes. Furthermore, drooping eyelids (ptosis) are frequently present, further restricting vision.

Researchers have identified several distinct forms of CFEOM, including CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome (sometimes referred to as CFEOM4). The specific eye movement limitations vary among these types, and some are associated with additional symptoms. Individuals with CFEOM1 and CFEOM2 primarily exhibit the eye-related issues described earlier. In CFEOM1, the eyes typically point downwards, while in CFEOM2, they usually turn outwards.

CFEOM3 can involve other neurological problems, such as intellectual disability, social skill deficits, an abnormally small head size (microcephaly), facial muscle weakness, non-functional vocal cords, and Kallmann syndrome. Kallmann syndrome is characterized by delayed or absent puberty and a diminished sense of smell. Some individuals with CFEOM3 may also develop pain, weakness, or reduced sensation in their limbs (peripheral neuropathy), starting in childhood or adulthood.

Brain abnormalities can also occur in individuals with CFEOM3. Some may exhibit abnormal development of the brain's white matter, which contains nerve cell fibers (axons) responsible for transmitting nerve impulses. A specific form of CFEOM3, known as CFEOM3 with polymicrogyria, involves abnormal brain development where the folds and ridges on the brain's surface are smaller and more numerous than usual.

Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities, in addition to the eye movement problems associated with CFEOM.

Inheritance:

The different forms of CFEOM are inherited in distinct ways. CFEOM1 and CFEOM3 follow an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene is needed in each cell to cause the disorder. In some cases, an affected individual inherits the mutation from a parent who also has the condition. In other instances, the mutation arises spontaneously (de novo) in the individual, with no prior family history of the disorder. CFEOM2 is inherited in an autosomal recessive manner, meaning that both copies of the gene in each cell must be mutated for the disorder to manifest. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not exhibit any signs or symptoms of the condition themselves. Tukel syndrome also appears to be inherited in an autosomal recessive pattern, although the specific genetic mutation responsible for this syndrome remains unknown.