Horizontal gaze palsy with progressive scoliosis

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects the eyes and the spine. Individuals with this condition are unable to move their eyes side-to-side (horizontally) from birth, although the problem may not be diagnosed until later in infancy. As a result, affected individuals must track moving objects by turning their head instead of moving their eyes. Up-and-down (vertical) eye movements are typically normal.

In people with HGPPS, an abnormal side-to-side curvature of the spine (scoliosis) develops between infancy and childhood. It tends to be moderate to severe and worsens over time. The abnormal spine position can be painful and can interfere with movement. In severe cases, it may impede breathing. It may require external support, such as bracing, and is often treated with surgery early in life.

People with HGPPS have structural abnormalities along the midline of the brain that can only be seen with medical imaging. This imaging shows distinctive malformations that include underdevelopment of brain structures called the pons and cerebellar peduncles and a notch or cleft in the midline of the brain. While most people with HGPPS have a normal intellect, mild intellectual disabilities can occur.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

HGPPS is caused by variants (also called mutations) in the ROBO3 gene. This gene provides instructions for making a protein that plays a critical role in the developing brain before birth. Specifically, this protein is important for communication across the two sides (hemispheres) of the brain.

The ROBO3 protein is important for forming certain nerve pathways in the brain. These include motor nerve pathways, which transmit information about voluntary muscle movement, and sensory nerve pathways, which transmit information about sensory input (such as touch, pain, and temperature). For the brain and the body to communicate effectively, these nerve pathways must cross from one side of the body to the other in the brainstem. The ROBO3 protein is necessary to ensure that motor and sensory nerve pathways can cross over in the brainstem. In people with HGPPS, these pathways do not cross over; they stay on the same side of the body.

Researchers believe that this miswiring in the brain caused by the lack of the ROBO3 protein is the underlying cause of the eye movement abnormalities that are associated with HGPPS. The cause of progressive scoliosis in people with this condition is unclear.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

HGPPS has been reported in several dozen families worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Horizontal supranuclear gaze palsy · Very frequent (99-80%)

A supranuclear gaze palsy is an inability to look in a horizontal direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Kyphosis · Very frequent (99-80%)

Exaggerated anterior convexity of the thoracic vertebral column.

Scoliosis · Very frequent (99-80%)

The presence of an abnormal lateral curvature of the spine.

Cognitive impairment · Frequent (79-30%)

Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.

Delayed skeletal maturation · Frequent (79-30%)

A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.

Duane anomaly · Frequent (79-30%)

A condition associated with a limitation of the horizontal ocular movement with retraction of the globe and narrowing of the palpebral fissure on adduction

Hypotonia · Frequent (79-30%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Microcephaly · Frequent (79-30%)

Head circumference below 2 standard deviations below the mean for age and gender.

Other findings in the same source

From: Orphanet

Additional reported features include Myopathy (Frequent (79-30%)); Nystagmus (Frequent (79-30%)); Proportionate short stature (Frequent (79-30%)); Short neck (Frequent (79-30%)); Strabismus (Frequent (79-30%)); Visual impairment (Frequent (79-30%)); Seizure (Occasional (29-5%)); Sensorineural hearing impairment (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Horizontal gaze palsy with progressive scoliosis is Ophthalmology, with a ophthalmologist as the relevant type of clinician. Ophthalmologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which part of the eye or visual pathway is affected?
• What change in vision requires immediate contact with the eye service?
• What are the aims and alternatives of any proposed eye treatment?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.