Septo-Optic Dysplasia Health Article

Definition

Septo-optic dysplasia (SOD) is a rare congenital disorder that includes underdevelopment of the nerves at the back of the eye(s), absence of a part of the brain called the septum pellucidum and/or corpus callosum, and dysfunction of the pituitary gland that produces hormones in the body.

Description

SOD is also known as DeMorsier's syndrome and is commonly recognized as the association of three features: underdevelopment of the optic nerves (optic nerve hypoplasia), absence of midline structures of the brain (most often the septum pellucidum), and problems with the functioning of the pituitary gland in the brain that controls hormone production in the body. These three features of SOD most often cause partial or complete blindness and mild to severe visual problems, difficulty with coordination of mental and muscular activities, such as walking, and short stature. Individuals with SOD may have normal intelligence, or learning problems that can range from mild to severe.

Genetic profile

Most often, SOD occurs sporadically and is not inherited. For most individuals with SOD, there is no family history of the condition. However, there have been a few familial cases reported. Benner et al., in 1990, reported a brother and sister both with features of SOD. In addition, Wales and Quarrell in 1996 reported a family in which the parents were related and had both a son and daughter with SOD. These families raise the possibility that there is a form of SOD that is inherited in an autosomal recessive pattern. In autosomal recessive inheritance, two unaffected parents both carry a mutation in a single copy of a gene for a condition. When both parents pass the mutated gene on to a child, the child with two copies of the gene mutation is affected with the condition. People who are related by blood are more likely to be carriers of mutations in the same gene since they inherit their genes from a common ancestor.

Mutations in a gene called HESX1 located on the upper short arm of chromosome 3 have been identified in some people with SOD. The brother and sister whose parents were related were both found to have mutations in both copies of their HESX1 genes. A 2001 study of 228 individuals with SOD or features of SOD revealed that three had a mutation in one copy of their HESX1 gene. One Japanese individual with features of SOD was also found to have a mutation in one copy of his HESX1 gene. Therefore, it is likely that HESX1 is fully or partially causative in a small subset of individuals with SOD. The product of the HESX1 gene is expressed in the brain in early development and has been shown to be involved in the development of structures that give rise to the pituitary gland. In 1998, a strain was created in mice with mutations in the HESX1 gene so that no product was made from the gene. These mice had features similar to individuals with SOD, including pituitary gland dysfunction as well as structural changes in the brain and eyes.

Other causes of SOD are thought to be related to viral infections, diabetes, anti-seizure medications, alcohol, and illicit drug use during pregnancy. In addition, a 2004 study suggested that amniotic bands may be responsible for SOD in some patients. Amniotic bands are formed when the inner membrane of the sac holding the fluid around a fetus tears. Pieces of the amnion may wrap around various parts of the fetus and restrict blood flow to those areas. Limb malformations have been shown to be caused by amniotic bands in some cases. However, in 2004 it was suggested that limb malformations are a recurrent feature of SOD, rather that SOD being caused by amniotic bands.