It is estimated that 1 in 10,000 newborns are affected by De Morsier syndrome. It affects males and females equally but appears to be more common in children born to younger mothers. 

The cause of De Morsier syndrome is mostly unknown. In rare cases, a mutation in one or more of four genes involved in early development can be detected. HESX1, SOX2, SOX3, and OTX2 are genes involved in the development of the eyes, the pituitary gland, the structures in the midline of the brain, and the optic nerve. Although De Morsier syndrome usually occurs in individuals with no family history and is not inherited, there have been reports of this syndrome running in families. In such cases, it is mostly inherited in an autosomal recessive pattern, meaning that both parents have a defect in one of the associated genes but appear healthy. The affected child inherits the defective copy from both parents, resulting in the presentation of symptoms. In a few instances, De Morsier syndrome has been inherited as an autosomal dominant syndrome, meaning that the individual only needs to inherit a defective copy from one parent to exhibit the disease. 

Since mutations in these genes are present in only a small number of individuals affected by De Morsier syndrome, environmental factors such as maternal drug and alcohol abuse, viral infection, or the disruption of blood flow to the fetus have been suggested as possible contributing factors. De Morsier syndrome appears to involve abnormalities in early development, occurring at the 4th to the 6th weeks of pregnancy.

The severity and type of symptoms of De Morsier syndrome differ 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.

The diagnosis of De Morsier syndrome is clinical, based on the presence of two or more features that characterize it. These features are the underdevelopment of the optic nerve, abnormalities in the production of pituitary hormones, and defects in structures along the midline of the brain. In presence of two or more of these features, further visual assessment, medical imaging techniques, and hormonal studies can be performed to confirm the diagnosis.

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.

There is currently no cure for De Morsier syndrome and treatment targets specific symptoms. If hormonal deficiencies exist, hormone replacement therapy can be beneficial. Hormonal replacement therapy involves the administration of hormones that are not produced sufficiently by the body. Furthermore, children may benefit from developmental services for individuals with visual impairment, as well as receiving physical and occupational therapy.

Individuals with De Morsier syndrome have highly variable prognoses, depending on the severity and types of symptoms present. With early diagnosis and prompt management of hormonal abnormalities, the outlook improves.

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