Optic Nerve Hypoplasia

Optic Nerve Hypoplasia / Hypopituitarism

(previously known as Septo-optic Dysplasia)

What is Optic Nerve Hypoplasia / Hypopituitarism?  This rare condition is associated with small or underdeveloped optic nerves, abnormal formation of structures along the midline or middle of the brain, and hypoplasia or underdevelopment of the pituitary gland.  It is diagnosed in 1 out of 10,000 newborns.  Other names for this condition are septo-optic dysplasia (SOD) and de Morsier syndrome.  The term ‘Optic Nerve Hypoplasia / Hypopituitarism’ is favored, as all affected children have the optic nerve problem, but only half have the midline ‘septo’ abnormalities.

Each of these features will be reviewed below in further detail.

• Optic nerve hypoplasia (underdevelopment): The optic nerves run from the back of the eye to the back of the brain where the images that we see are processed.  An ophthalmologist or eye doctor is specially trained to look at the optic nerve and tell whether it is normal in size or small.  Children can often present with nystagmus which is an abnormal movement (jiggling) of the eyeballs, sometimes described as ‘roving or wandering eyes’ or rapid eye movements.  Children with optic nerve hypoplasia (ONH) can have difficulty focusing on the face of a parent/caregiver or another object starting in infancy.  The vision of a child with ONH/Hypopituitarism can be quite variable ranging from normal to almost blind, or anywhere in between.
• Abnormal formation of midline (middle) structure of the brain: About 50% of children with ONH/Hypopituitarism have absence of a midline brain structure known as the septum pellucidum which separates the ventricles (fluid-filled areas of the brain).  In addition, the corpus callosum, the midline structure that separates the right and left sides of the brain, can be missing.  Children with these abnormalities can have seizures or intellectual disabilities.  Alternatively, their neurologic function can be normal.
• Hypopituitarism due to pituitary gland hypoplasia:  The pituitary gland secretes a variety of important hormones. A child with ONH/Hypopituitarism can be missing one or multiple pituitary hormones.  Some children are not missing any hormones.  Each potential hormone is listed below along with a description of symptoms associated with a deficiency of that hormone.
  • Growth hormone: Symptoms of low growth hormone include slow growth and short stature.  A baby can also have low blood sugar if this hormone is missing.  This is the most commonly missing pituitary hormone.
  • Thyroid-stimulating hormone or TSH: This hormone controls production of thyroid hormone which, if missing, can cause poor growth, low energy, dry skin, constipation, feeling cold frequently, more weight gain than height gain, and, in some cases, delayed intellectual and physical development.
  • Gonadotropins (luteinizing hormone or LH and follicle-stimulating hormone or FSH): These hormones are important for the initiation of puberty.  A young boy with a deficiency of these hormones can have a small penis size or testicles that haven’t descended into the scrotum.
  • Adrenocorticotropic hormone (ACTH): This hormone stimulates the release of cortisol from the adrenal glands.  Cortisol is an important hormone when our bodies are in a state of stress.  Cortisol helps maintain our blood pressure and blood sugar amongst other things.  A child who is missing cortisol can be very weak, tired, dizzy, or have a poor appetite.
  • Anti-diuretic hormone (ADH): This hormone helps the kidneys concentrate urine when a child is dehydrated. If this hormone is missing, a person will urinate frequently and be very thirsty.  A child who is unable to communicate well (like an infant or a child with an intellectual disability) can become very dehydrated due to an inability to verbalize a sense of thirst.
  • Prolactin: This hormone is ordinarily responsible for milk formation in mothers who breast-feed their infants.  Lower levels are normally present in both girls and boys, with slight elevations found frequently in infants and children with ONH/Hypopituitarism.

What causes ONH/Hypopituitarism?

Unfortunately, the cause of ONH/Hypopituitarism is not entirely known.  There have been a few genetic variations found in patients with ONH/Hypopituitarism.  Your doctor may choose to test your child for these variations.  HESX1, OTX2, and SOX2 genes all play a role in the early development of the brain, eyes, and pituitary gland.  A variation in one of these genes can lead to ONH/Hypopituitarism.

Typically these variations are sporadic meaning they are not passed down from parent to child, so there is no risks of recurrence.  However, there are some variations that do run in families.

How is ONH/Hypopituitarism diagnosed?

Most commonly, the abnormal eye movement is the first clue for ONH/Hypopituitarism.  Sometimes one of the pituitary hormones is missing and may provide an early clue that the child has ONH/Hypopituitarism.  An MRI of the brain may be ordered to get an inside look into how the brain has developed.  Finally, genetic testing can be used to diagnose ONH/Hypopituitarism.

A child does not have to have all 3 features (meaning optic nerve hypoplasia, abnormal midline structures of the brain, and pituitary gland hypoplasia) to be diagnosed with ONH/Hypopituitarism.  A child can have 2 of the 3 and still be diagnosed with ONH/Hypopituitarism.

How is ONH/Hypopituitarism treated?

There is no treatment to cure ONH/Hypopituitarism.  Typically, each symptom that develops is treated by an appropriate specialist.  For example, an ophthalmologist can prescribe glasses or recommend certain therapies to improve vision.  If your child has seizures, a neurologist can provide anti-seizure medication.  If your child is missing a pituitary hormone, an endocrinologist can prescribe treatment to replace the missing hormone.  An affected child may not have to see each of these doctors for life; it depends on what problems the child has.  It is important to note that, even though a child may not have a pituitary hormone deficiency initially, one can still develop later on in life.  Please see other hand-outs on the Pediatric Endocrine Society website for more information on treatment of specific hormone deficiencies.

References:

Ghr.nlm.nih.gov/condition/septo-optic-dysplasia

 

Pediatric Endocrine Society

Section on Endocrinology Patient Education Committee