Septo-Optic Dysplasia

What is Septo-Optic Dysplasia?

Septo-optic dysplasia (SOD) is a very rare disorder that is characterized by the abnormal development of optic disk, pituitary problems as well as agenesis or absence of septum pellucidum, the portion of the brain responsible for separating the anterior horns or lateral ventricles of the brain. Other intracranial malformations include lobar holoprosencephaly and schizencephaly.

The condition is also referred to as de Morsier syndrome.

Septo-Optic Dysplasia Epidemiology

Septo-optic dysplasia is a rare disorder, occurring only in case of one out of every 100,000 individuals of the population. It is more common in areas where there is low income, high unemployment and more number of teenage pregnancies. Although a link has been suggested between the disorder and young mothers, the significance of maternal age is still under debate.

Septo-Optic Dysplasia Causes

SOD is a congenital condition that is believed to be a part of holoprosencephaly spectrum. Common features may include blindness in either or both the eyes, nystagmus, hypotonia, pupil dilation under the presence of light, outward and inward deviation of eyes, seizures and hormonal problems. The intellectual problems might vary in intensity among the affected individuals. While some children affected by this syndrome may have normal intelligence, others can face learning difficulties and mental retardation. Most face developmental delay due to neurological problems or vision impairment.

Septo-optic dysplasia is said to be a developmental disorder that results from defective embryological development.  No single factor can be held responsible for the occurrence of this disease. However, SOD has been associated to a young maternal age.

Familial recurrence has been reported in some rare cases, suggesting the presence of at least one genetic form involving the HESX1 gene. Apart from this, mutations in the neuronal guidance chemical netrin as well as its receptor DCC are believed to play an important role in the de Morsier’s syndrome. In most cases, however, SOD is a birth defect that occurs sporadically and doesn’t recur with each subsequent pregnancy.

Environmental factors such as exposure to various recreational drugs such as cocaine can greatly interfere with in utero cerebral development of the fetus. Another probable causative factor for this condition is in utero valproate toxicity.

Septo-Optic Dysplasia Genetics

The disorder results from a mutation in the gene locus referred to as 3p21.2-p21.1 which is responsible for controlling HESX1, a vital regulator of pituitary development. Although SOD appears as genetic in its origin, it barely runs in families; a feature that suggests that the mutation is mostly spontaneous than inherited. Researchers have claimed that no Mendelian basis have been found for the disorder. However, a single report involving an occurrence in a brother–sister duo raises the probability that it might have an autosomal recessive trait. The condition has been also reported in two siblings from a consanguineous marriage.

Septo-Optic Dysplasia Symptoms

Numerous signs and symptoms associated with SOD include:

Optic Nerve Hypoplasia

The clinical feature of optic nerve hypoplasia is commonly manifested by nystagmus, a condition which involves involuntary eye movements, frequently from side-to-side and an optic disc that is smaller than usual. The degree to which visual impairment occurs can vary from one patient to another, and may range from a normal vision to a complete blindness. The initial onset of nystagmus occurs when the child is around 1 to 8 months of age. It generally indicates that there will be a significant level of visual impairment. However, the severity of such impairment is difficult to foresee in infancy. Even though there are several measures to alleviate the symptoms of visual impairment, only a few treatment procedures can induce normal optic nerve functionality.

Pituitary Problems

The extent of pituitary deficiencies is also quite variable. The pituitary functions can read normal, or deficiencies relating to both posterior and anterior hormones may be found. It is frequently unclear as to whether the hypopituitarism is caused by some primary pituitary dysfunction or if it is secondary to some hypothalmic dysfunction. Hypopituitarism in septo-optic dysplasia is most frequently manifested by a growth hormone deficiency. Under severe conditions, it may lead to a diagnosis within the first few days of life by causing jaundice, micropenis (in boys), and hypoglycemia. The factors leading to jaundice are not known as compared to most cases of neonatal jaundice. An unusual feature of the condition is that it largely presents signs of a conjugated or direct hyperbilirubinemia that suggests an obstructive liver disease. The condition typically resolves over a number of weeks once hormone therapy is started. It is possible to replace all of the various pituitary hormones, and this is considered to be the standard of treatment for hormonal deficiencies. SOD can be considered among the most commonly occurring types of congenital growth hormone disorder.

Septum pellucidum

The effects of SOD on the brain are also quite variable. Seizures may occur on some occasions. It is difficult to predict the outcome of intellectual disability during infancy.

A number of other signs and symptoms are commonly associated with this disorder. These include the following:

• Autism
• Astigmatism
• Blindness that affects one or both the eyes
• Ectopic posterior pituitary, which might be present
• The visual apparatus might be severely affected
• Signs of hypoglycemia may be observed during the neonatal period
• Hypoplastic optic discs can be seen with one classical double margin
• Some form of psychomotor impairment can be seen in majority of patients
• Hypothalamic-pituitary dysfunction can be seen in around 60% to 80% of patients
• The olfactory bulbs might be absent (Kallmann Syndrome)
• The septum pellucidum with or without corpus callosum might be absent in around 50% of the patients
• Other midline abnormalities can be observed in the fornix, the corpus callosum, the septum pellucidum, and the cerebellum
• A consistent clinical sign is short stature that is associated with absent or lack of adequate growth hormone. The head circumference and weight are considered normal for size.
• Possible signs of hypernatraemia and precocious puberty
• Possible deficiency in thermoregulation
• Possible adrenal crisis and/or sudden death due to lack of adequate adrenocorticotrophic hormone (ACTH)

Signs associated with schizencephaly include the following:

• The condition may have a different etiology
• The optic apparatus might be less severely affected
• The condition might be sometimes indicated as septo-optic dysplasia plus

Septo-Optic Dysplasia Diagnosis

The following tests are conducted to evaluate whether or not a person is having SOD:

• Brain imaging using CT scans and MRI scans are useful in measuring the size of optic nerves. MRI helps in indicating the degree of the structural abnormalities as well as indicates towards the probable endocrine abnormality.
• Developmental assessment can show retardation and delayed mental progress.
• Tests of pituitary functions may reveal hypopituitarism.

Septo-Optic Dysplasia Differential Diagnosis

A number of health conditions have signs and symptoms similar to that of SOD. Hence, while determining the presence of SOD, it is important to differentiate it from such similar disorders. The differential diagnoses of SOD include isolating its symptoms from those of various conditions such as:

• Aqueductal stenosis
• Kallmann’s syndrome
• Chiari II malformation
• Lobar holoprosencephaly
• Rhomboencephalosynapsis
• Dysgenesis of corpus callosum
• Dysgenesis of the microphthalmos
• Optic infundibulum dysplasia (OID) with Schizencephaly but normal septum pallucidum

Septo-Optic Dysplasia Treatment

The treatment for SOD is mostly symptomatic. The hormonal deficiencies can be treated by using hormone replacement therapy. Psychomotor retardation that is complicated by weak vision requires the attention of a specialist. Occupational and physical therapies are required to manage various symptoms and difficulties. The optical problems linked with SOD are commonly not treatable. A life-long multidisciplinary approach is required to facilitate optimum growth and development.

Septo-Optic Dysplasia Prognosis

The appearance of septum pellucidum and the hypothalamic-pituitary axis on the MRI scans may predict the probable spectrum of the endocrine disorder. Prognosis depends on the severity of symptoms. Early diagnosis increases the chances of a better outcome.