Christianson syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Christianson syndrome is a disorder that primarily affects the nervous system. This condition becomes apparent in infancy. Its characteristic features include delayed development, intellectual disability, an inability to speak, problems with balance and coordination (ataxia), and difficulty standing or walking. Individuals who do learn to walk lose the ability in childhood. Most affected children also have recurrent seizures (epilepsy), beginning between ages 1 and 2.

Other features seen in many people with Christianson syndrome include a small head size (microcephaly); a long, narrow face with prominent nose, jaw, and ears; an open mouth and uncontrolled drooling; and abnormal eye movements. Affected children often have a happy demeanor with frequent smiling and spontaneous laughter.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Christianson syndrome is caused by mutations in the SLC9A6 gene, which provides instructions for making a protein called sodium/hydrogen exchanger 6 (Na+/H+ exchanger 6 or NHE6). The NHE6 protein is found in the membrane surrounding endosomes, which are compartments within cells that recycle proteins and other materials. The NHE6 protein helps exchange positively charged atoms (ions) of sodium (Na+) with hydrogen ions (H+) across the endosomal membrane. By controlling the amount of hydrogen ions, the NHE6 protein helps regulate the relative acidity (pH) inside endosomes, which is important for the recycling function of these compartments. The NHE6 protein may have additional functions, such as helping to move proteins to the correct location in the cell (protein trafficking).

Mutations in the SLC9A6 gene typically lead to an abnormally short NHE6 protein that is nonfunctional or that is broken down quickly in cells, resulting in the absence of functional NHE6 proteins. As a result, the pH in endosomes is not properly maintained. It is unclear how unregulated endosomal pH leads to neurological problems in people with Christianson syndrome. Some studies have shown that protein trafficking by endosomes is important for learning and memory, but the role of endosomal pH or the NHE6 protein in this process has not been identified.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene but usually does not experience signs and symptoms of the disorder. Occasionally, however, females who carry an SLC9A6 gene mutation have mild learning disabilities. It is unclear if these disabilities are related to the gene mutation or occur by chance.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Christianson syndrome is a rare condition, although the exact prevalence is unknown. The condition was first described in a South African family and has since been found people in other parts of the world.

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.

Absent speech · Very frequent (99-80%)

Complete lack of development of speech and language abilities.

Cachexia · Very frequent (99-80%)

Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease.

Developmental regression · Very frequent (99-80%)

Loss of developmental skills, as manifested by loss of developmental milestones.

Generalized-onset seizure · Very frequent (99-80%)

A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.

Intellectual disability, profound · Very frequent (99-80%)

Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20.

Long face · Very frequent (99-80%)

Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).

Macrotia · Very frequent (99-80%)

Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).

Narrow face · Very frequent (99-80%)

Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).

Other findings in the same source

From: Orphanet

Additional reported features include Severe global developmental delay (Very frequent (99-80%)); Strabismus (Very frequent (99-80%)); Thick eyebrow (Very frequent (99-80%)); Truncal ataxia (Very frequent (99-80%)); Neuronal loss in central nervous system (Very frequent (99-80%)); Abnormal repetitive mannerisms (Frequent (79-30%)); Abnormal thorax morphology (Frequent (79-30%)); Adducted thumb (Frequent (79-30%)); Aplasia/Hypoplasia of the corpus callosum (Frequent (79-30%)); Autism (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Christianson syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

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.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Christianson syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

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.