Septo-Optic Dysplasia

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Septo-optic dysplasia


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.


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.


The incidence of SOD is not known, but the condition is considered to be rare. SOD does not occur more often in males or females and is not known to occur more or less frequently in any racial or ethnic group. SOD may become apparent during infancy, childhood, or in adolescence.

Signs and symptoms

A variety of changes in the structure and function of the eye(s) can occur as part of SOD. Most commonly, individuals have optic nerve hypoplasia, meaning that the nerves from the back of the eye to the brain are underdeveloped. The nerves may be small, and there are usually far fewer nerves connecting the eye to the brain than usual. The optic disk (the front surface of the optic nerve) may also be smaller than usual. Infants with SOD may have rapid, involuntary eye movements called nystagmus. Other changes in the structure of the eye may occur, such as strabismus (the eyes can not focus on the same object at the same time), coloboma (notch-like area of absent tissue), and micropthalmia (small openings of the eyes). The optic features of SOD may affect one or both eyes, so that an individual with the condition may have good vision in one eye, or may have decreased or no vision in both eyes.

There can also be a variety of structural changes to the brain in people with SOD. Most often, a membrane in the midline of the brain called the septum pellucidum is absent. This membrane separates the fluid-filled cavities on each side of the brain. Another midline structure, the corpus callosum, may also be absent or underdeveloped. The corpus callosum is the thick band of nerve fibers that connects the two hemispheres of the brain. In addition, the region of the brain that controls voluntary movement, the cerebellum, may be underdeveloped. Other structural brain malformations have been reported in individuals with SOD.

Additional structures in the brain that can be affected in individuals with SOD include the hypothalamus and the pituitary gland. These parts of the brain control the production and release of hormones in the body. Individuals with SOD may not produce enough growth hormone and may exhibit short stature. There may be problems with the production of hormones needed for sexual development, low blood sugar, dehydration, and seizures.

Various other conditions have been reported in individuals with SOD. These include cleft lip and/or palate, limb anomalies, including fusion of fingers or toes and underdevelopment of fingernails or toe nails, and apnea (difficulty breathing).

Patients affected with SOD can present at any age depending on the severity of the symptoms. Signs and symptoms, including failure to thrive, prolonged jaundice (yellow color to the skin caused by extra amounts of bile in the blood), difficulty controlling body temperature, decreased blood sugar, small genitalia, or low muscle tone, can herald the diagnosis of SOD in newborns. Older children may complain of visual difficulties, or have the inability to fixate on an object.

Many individuals with SOD have normal intelligence. However, there is a range of intelligence reported, including those with mild learning delays and those with significant mental retardation. Learning delays and mental retardation may be the result of structural changes in the brain or hormone disorders. Unrecognized visual problems or lack of education appropriate for those with visual impairment may also cause learning delays.


SOD is often suspected when a child with visual impairment also has growth delay. When a diagnosis of SOD is suspected, a person is referred to several specialists who each perform tests to verify the diagnosis. An ophthalmologist can perform vision testing and examinations of the structure of the eye for features of SOD. In individuals with SOD, the optic nerves appear small and gray or pale in color and can be surrounded by a double pigmented ring or margin. In addition, stimulation testing of the optic nerves can be performed. A neurologist (brain specialist) can perform imaging studies of the brain, such as magnetic resonance imaging (MRI) or computerized tomography (CT) scan of the brain, focusing on the visual pathways, the septum pellucidum, hypothalamus-pituitary region, and other midline structures. An endocrinologist can perform blood tests to determine if there are problems with various hormones in the body.

There has been a report of prenatal diagnosis of SOD by an ultrasound that revealed absence of the septum pellucidum. Subsequent blood and urine tests on the mother revealed low levels of the hormone estriol, indicating a problem with the fetal pituitary gland. The diagnosis was confirmed after birth.

Treatment and management

SOD is treated symptomatically. Vision may be improved with corrective lenses, surgery or other treatment. Seizures may be controlled with medication. Hormone deficiencies are managed with hormone replacement therapy, such as growth hormones or thyroid supplements. Hormone problems may arise at different ages, so even if not present initially, a person with SOD should be followed by an endocrinologist over time. Children with SOD should receive early assessments of learning and development so that any supportive therapies, such as physical, speech, or educational therapy, can be initiated. Children with SOD may benefit from an individualized educational plan (IEP) in school, which is a plan created by a child's teachers, therapists, and other individuals who have performed developmental testing and designed techniques best suited to the child's needs. Families may consider placing a child with SOD in a school for visually impaired children. The child's pediatrician can monitor a child for any special needs and refer additional specialists as needed. Individuals and families with SOD may benefit from talking with a genetic counselor about possible patterns of inheritance and recurrence risks for SOD in the family. Families should also be introduced to the appropriate local and national support organizations, such as the American Foundation for the Blind, for further help and assistance.


Prognosis is variable, depending on the number and severity of features present. Most individuals with SOD have significant visual impairment, and many are legally blind. Patients with severe visual impairment may have difficulty obtaining a driver's license or gainful employment. Lifespan is most often normal, however, cortisol deficiency can lead to life-threatening episodes brought about by infection or stress.



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Sonja R. Eubanks, MS, CGC