What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Horizontal Gaze Palsy with Progressive Scoliosis
• HGPPS (Horizontal Gaze Palsy with Progressive Scoliosis)
• Progressive External Ophthalmoplegia and Scoliosis

What is Horizontal Gaze Palsy with Progressive Scoliosis? (Definition/Background Information)

• Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) is a rare disorder that affects vision and also causes an abnormal curvature of the spine (scoliosis)
• People with this condition are unable to move their eyes side-to-side (horizontally) and must turn their head instead of moving their eyes to track moving objects
• Scoliosis develops in infancy or childhood and worsens over time. Scoliosis can be painful and may interfere with movement so it is often treated with surgery early in life
• HGPPS is caused by changes (mutations) in the ROBO3 gene and is inherited in an autosomal recessive manner
• The treatment of Horizontal Gaze Palsy with Progressive Scoliosis is based on the signs and symptoms present in each person

(Source: Horizontal Gaze Palsy with Progressive Scoliosis; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Horizontal Gaze Palsy with Progressive Scoliosis? (Age and Sex Distribution)

• Horizontal Gaze Palsy with Progressive Scoliosis is a rare congenital disorder. The prevalence of the disorder is not known
• The presentation of symptoms typically occurs in infancy or childhood. However, manifestation of the disorder may also occur during adolescence and early adulthood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Horizontal Gaze Palsy with Progressive Scoliosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Horizontal Gaze Palsy with Progressive Scoliosis can be inherited
• Choldren born to consanguinepus parents may bear an increased risk of developing this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Horizontal Gaze Palsy with Progressive Scoliosis? (Etiology)

• Horizontal Gaze Palsy with Progressive Scoliosis is caused by mutation(s) in ROBO3 gene
• This gene codes for a protein that is necessary for normal development of the nervous system. The ROBO3 protein is active in the brainstem and developing spinal cord
• Causative mutation(s) in the ROBO3 gene are inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Horizontal Gaze Palsy with Progressive Scoliosis?

The signs and symptoms of Horizontal Gaze Palsy with Progressive Scoliosis may vary among affected individuals in type and severity.

Based on the frequency of symptoms observed, the following information may be noted:

• Cognitive impairment
• Horizontal supranuclear gaze palsy
• Kyphosis
• Nystagmus
• Progressive ophthalmoplegia
• Scoliosis
• Sensorineural hearing impairment
• Thoracolumbar scoliosis

(Source: Horizontal Gaze Palsy with Progressive Scoliosis; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Horizontal Gaze Palsy with Progressive Scoliosis Diagnosed?

Horizontal Gaze Palsy with Progressive Scoliosis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative ROBO3 mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Horizontal Gaze Palsy with Progressive Scoliosis?

The complications of Horizontal Gaze Palsy with Progressive Scoliosis may include:

• Progressive weakening and/or paralysis of extraocular muscles, resulting in deterioration in movement of eyeballs
• Severe pain due to scoliosis
• Crowding of organs in the chest cavity
• Structural and functional abnormalities in functions of the heart and lungs
• Stroke
• Progressive worsening of scoliosis, such that it interferes with movement
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Horizontal Gaze Palsy with Progressive Scoliosis Treated?

There is no cure for Horizontal Gaze Palsy with Progressive Scoliosis, since it is a genetic condition.

• The treatment is usually given to manage the signs and symptoms and any complication that develops
• Treatment methods may include surgery to correct bone abnormalities (scoliosis and kyphosis) and other associated defects

How can Horizontal Gaze Palsy with Progressive Scoliosis be Prevented?

Horizontal Gaze Palsy with Progressive Scoliosis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Horizontal Gaze Palsy with Progressive Scoliosis? (Outcomes/Resolutions)

• The prognosis of Horizontal Gaze Palsy with Progressive Scoliosis is dependent upon the severity of the signs and symptoms and associated complications, if any
• Scoliosis is progressive in this disorder, and without treatment, may severely reduce one’s mobility and quality of life
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Horizontal Gaze Palsy with Progressive Scoliosis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/