Septo-optic dysplasia spectrum

Other Names: Septooptic dysplasia; De morsier syndrome; Septo-optic dysplasia with growth hormone deficiency; Hypopituitarism and septooptic 'dysplasia'; SOD; Septo-optic dysplasia

Septo-optic dysplasia is a disorder of early brain and eye development. The most common features are underdevelopment (hypoplasia) of the eye (optic) nerve, abnormal formation of structures along the midline of the brain such as the absence of the septum pellucidum and the corpus callosum, and a small pituitary (pituitary hypoplasia).

Epidemiology

Septo-optic dysplasia has a reported incidence of 1 in 10,000 newborns.

Cause

In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.

At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in embryonic development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.

Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia.

Inheritance

Septo-optic dysplasia is usually sporadic, which means that the condition typically occurs in people with no history of the disorder in their family.

Less commonly, septo-optic dysplasia has been found to run in families. Most familial cases appear to have an autosomal recessive pattern of inheritance, which means that both copies of an associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In a few affected families, the disorder has had an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the condition.

Signs and symptoms

Typically, the symptoms develop in 3 organs, the brain (which have abnormal formation of midline structures), the eyes (due to optic nerve hypoplasia), and pituitary (due to hypoplasia. About one third of the patients present with all of the three main features. However, some symptoms may not appear until childhood or later.

Symptoms may include:

• Blindness in one or both eyes
• Pupil dilation in response to light
• Nystagmus (a rapid, involuntary to-and-fro movement of the eyes)
• Inward and outward deviation of the eyes
• Hypotonia (low muscle tone)
• Seizures

Other common features are:

• Short stature due to lack of growth hormone deficiency (the most common hormonal abnormality)
• Abnormal thirst, hunger, and body temperature due to underdevelopment of the hypothalamus, a region of the brain responsible for regulating basic body functions.
• Low blood sugar
• Genital abnormalities
• Problems with sexual development or precocious puberty
• Sleep difficulties
• Obesity
• Jaundice
• Intellectual disability or learning disabilities
• Developmental delay related to vision impairment or neurological problems
• Anosmia
• Heart problems
• Pituitary hormone insufficiencies may evolve over time necessitating life-long medical follow-up.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Septo-optic dysplasia
• Visual impairment(Impaired vision)

30%-79% of people have these symptoms

• Agenesis of corpus callosum
• Anterior pituitary [[hypoplasia](Underdeveloped pituitary gland)
• Cleft palate(Cleft roof of mouth)
• Cryptorchidism(Undescended testes)
• Hemiplegia/hemiparesis(Paralysis or weakness of one side of body)
• Hypoplasia of penis(Underdeveloped penis)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Seizure
• Short stature(Decreased body height)
• Strabismus(Cross-eyed)

5%-29% of people have these symptoms

• Abnormality of cardiovascular system morphology
• Anosmia(Lost smell)
• Aplasia/Hypoplasiaof the cerebellum(Absent/small cerebellum)
• Autism
• Constipation
• Diabetes insipidus
• Dry skin
• Esophageal atresia(Birth defect in which part of esophagus did not develop)
• Fatigue(Tired)
• Global developmental delay(Hypohidrosis)
• Decreased ability to sweat
• Intellectual disability(Mental deficiency)
• Maternal diabetes(gestational diabetes)
• Obesity(Having too much body fat)
• Polydipsia(Extreme thirst)
• Sensorineural hearing impairment
• Sleep disturbance(Difficulty sleeping)
• Tracheoesophageal fistula

Diagnosis

A diagnosis of SOD is made when at least two of the following triad are present: optic nerve underdevelopment; pituitary hormone abnormalities; or mid-line brain abnormalities. Diagnosis is usually made at birth or during childhood, and a clinical diagnosis can be confirmed by MRI scans.

Treatment

Treatment is directed toward the specific symptoms in each individual and may require a team of specialists including pediatricians, ophthalmologists, neurologists, and endocrinologists. If present, hormone deficiencies may be treated with hormone replacement therapy. Vision problems are generally not treatable. Special services that may be useful include vision, physical, and occupational therapies.

Prognosis

The prognosis for individuals with septo-optic dysplasia varies according to the presence and severity of symptoms. Early diagnosis and treatment of hormone deficiencies (when present) allows for a better outcome for some associated symptoms.

NIH genetic and rare disease info

• NIH info on Septo-optic dysplasia spectrum

Septo-optic dysplasia spectrum is a rare disease.

Septo-optic dysplasia spectrum Resources
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