SOD has a reported incidence of approximately 1 in 10,000 live births. It impacts both genders equally.

As most cases of SOD are sporadic, a clear cause is not known, pointing towards a multifactorial origin involving both genetic and environmental influences. Mutations in genes involved in brain and pituitary gland development such as HESX1, SOX2, SOX3, and OTX2 have been associated with SOD in some individuals. Environmental risk factors include young maternal age, maternal diabetes, and exposure to certain medications, alcohol, viral infections or vascular injuries during pregnancy.

Symptoms of SOD may vary widely depending upon which components of the three main features (optic nerve hypoplasia, midline brain abnormalities and pituitary dysfunction) are present.

Visual Symptoms

• Partial to complete vision loss

• Nystagmus (involuntary eye movement)

• Strabismus (misalignment of eyes)

Neurological & Developmental

• Seizures

• Developmental delay

• Learning disabilities

• Hypotonia or motor delays

• Intellectual disability (in some cases)

Endocrine Symptoms (from pituitary dysfunction)

• Growth hormone deficiency, resulting in short stature

• Hypothyroidism

• Adrenal insufficiency

• Delayed or precocious puberty

• Low blood sugar

• Diabetes insipidus (excessive urine production)

The severity and type of symptoms of SOD differs among individuals. About one-third of affected individuals experience all three associated clinical manifestations: underdevelopment of the optic nerve, underdevelopment of the pituitary gland, and the abnormal formation of the structures along the midline of the brain. In some individuals, symptoms and anomalies may be present at birth, in others they may develop later in childhood.

Optic nerves may be affected in only one side or both sides, leading to loss of clear vision (low visual acuity), significant visual impairment, and even blindness in one eye or both eyes. In healthy individuals, the black center of the eyes (pupil) dilate or constrict in response to changes in the brightness of the environment to adjust the amount of light that enters the eyes. Individuals affected by De Morsier syndrome may experience abnormal dilation in response to light. They may also experience episodes of repetitive, uncontrolled movement of the eyes (nystagmus), and inwardly or outwardly deviated eyes. Low muscle tone is also a common symptom that results in muscles feeling floppy which makes it difficult to move muscles properly or maintain a good posture. 

The most common symptom of the underdevelopment of the pituitary gland is short stature. This is because the pituitary gland regulates the production of growth hormone which stimulates growth. Other symptoms associated with deficiency of other hormones or the abnormal formation of brain structures include excessive thirst or hunger, inability to regulate body temperature, obesity, low blood sugar, abnormalities in genital organs, early puberty, and sleep disturbances.  

Affected individuals may have seizures, developmental delay, and cerebral palsy. Cerebral palsy is a movement disorder that causes poor movement coordination, muscle stiffness, muscle weakness, and tremors.

Clinical diagnosis of SOD requires at least two of the three key features (optic nerve hypoplasia, midline brain defects, pituitary hormone abnormalities).

Diagnostic tools include:

• MRI of the brain to assess structural abnormalities

• Blood tests for pituitary hormone (GH, ACTH, TSH, LH/FSH) levels

• Ophthalmologic evaluation for optic nerve hypoplasia and vision assessment

• Developmental and neurological assessments

• Genetic testing to identify associated mutations in some cases.

To confirm the diagnosis of De Morsier syndrome, a Magnetic Resonance Imaging (MRI) is typically performed to assess the size and location of the pituitary gland and other associated structures. An MRI also allows for the evaluation of the optic nerve as well as midline brain structures such as the corpus callosum which connects the left and right hemispheres of the brain. Additionally, different tests can be performed to test the function of the pituitary gland. The pituitary gland releases growth hormone into the bloodstream to stimulate growth and regulates the production of hormones by other organs such as the thyroid gland, adrenal gland, and gonads (testes and ovaries). Consequently, tests that assess the function of these glands can provide insight into the function of the pituitary gland.

No cure exists for SOD;  management focuses on treating symptoms and preventing complications using a multidisciplinary approach to optimize growth and development.

• Hormone deficiencies are treated with hormone replacement therapy (e.g., growth hormone, cortisol, thyroid hormone).

• Vision support includes low vision aids and therapy.

• Developmental, physical and occupational therapies are tailored to the patient’s needs.

• Early intervention and coordinated care are critical for optimal outcomes.

The prognosis for individuals with SOD is highly variable, depending on the specific nature and severity of their symptoms. In mild cases, there is near-normal development with hormone and vision support. For severe cases, there may be significant visual, developmental and hormonal impairments. Life expectancy is generally normal, and early diagnosis and intervention can improve outcomes dramatically.

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