GENE GUIDE

SLC9A6-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has SLC9A6-Related Syndrome.
a doctor sees a patient

SLC9A6-related syndrome is also called Christianson syndrome and intellectual developmental disorder, X-linked syndromic, Christianson type. For this webpage, we will be using the name SLC9A6-related syndrome to encompass the wide range of variants observed in the people identified.

SLC9A6-related syndrome happens when there are changes to the SLC9A6 gene. These changes can keep the gene from working as it should. The SLC9A6 gene has also been called NHE6.

Key Role

The SLC9A6 gene plays a key role in controlling other genes, especially in a region of the brain called the cerebral cortex.

Symptoms

Because the SLC9A6 gene is important for brain activity, many people who have SLC9A6-related syndrome have:

  • Seizures
  • Severe intellectual disability, developmental delay, or both
  • Small head
  • Delayed or absent speech
  • Movement disorders
  • Regression, which may involve losing words or the ability to walk
  • Low muscle tone
  • Muscle contractures
  • Autism or features of autism
  • Sleep problems
  • Brain changes observed on magnetic resonance imaging (MRI)

SLC9A6-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Genes are arranged in structures in our cells called chromosomes. Chromosomes and genes usually come in pairs, with one copy from the mother, from the egg, and one copy from the father, from the sperm. 

We each have 23 pairs of chromosomes. One pair, called the X and Y chromosomes, differs between biological males and biological females. Biological females have two copies of the X chromosome and all its genes, one inherited from their mother and one inherited from their father. Biological males have one copy of the X chromosome and all its genes, inherited from their mother, and one copy of the Y chromosome and its genes, inherited from their father. 

In most cases, parents pass on exact copies of the gene to their child. But the process of making the sperm and egg is not perfect. A variant in the genetic code can lead to physical issues, developmental issues, or both. 

The SLC9A6 gene is located on the X chromosome, so variants in this gene can affect biological males and biological females in different ways. Biological males who have variants in this gene will likely have SLC9A6-related syndrome. 

Biological females who have variants in this gene may or may not have symptoms of SLC9A6-related syndrome. Biological females who have one working copy of the gene and one non-working copy are considered to be ‘carriers’. Even if a biological female does not have signs or symptoms of the syndrome, they can pass it along to their children.

X-linked recessive conditions

Research shows that SLC9A6-related syndrome is often the result of an inherited variant in SLC9A6. This means that SLC9A6-related syndrome happens because the genetic variant was passed down from a biological female parent. Biological females that carry the SLC9A6 variant usually do not have symptoms, but sometimes they might. 

Sometimes it results from a spontaneous variant in the SLC9A6 gene in the sperm or egg during development. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child can be the first in the family to have the gene variant.

X-Linked Recessive Genetic Syndrome

Sex chromosomes
Non-carrier father
Carrier mother
Sex chromosomes
Non-carrier female
Carrier female
Male child with X-linked
genetic condition
Non-carrier
male

Why does my child have a change in the SLC9A6 gene?

No parent causes their child’s SLC9A6-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family. 

The risk of having another child who has SLC9A6-related syndrome depends on the genes of both biological parents. 

  • Biological females who have a variant in the SLC9A6 gene and are pregnant with a daughter have a 50 percent chance of passing on the same genetic variant and a 50 percent chance of passing on the working copy of the gene. 
  • If they are pregnant with a son, the child has a 50 percent chance of inheriting the genetic  variant and the syndrome. 

For a symptom-free brother or sister of someone who has SLC9A6-related syndrome, the sibling’s risk of having a child who has SLC9A6-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing SLC9A6-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SLC9A6-related syndrome. 
  • If the biological mother has the same genetic variant causing SLC9A6-related syndrome, and the symptom-free daughter has the variant, the symptom-free daughter’s chance of having a son who has SLC9A6-related syndrome is 50 percent. 

For a person who has SLC9A6-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, about 95 people with SLC9A6-related syndrome have been described in medical research.

People who have SLC9A6-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Small head
  • Low weight and short height
  • A long, narrow face
  • Thick eyebrows
  • Eyes that look in different directions
  • A mouth held in an open position, with drooling

Scientists and doctors have only just begun to study SLC9A6-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

  • Physical exams and brain studies
  • Genetics consults
  • Development and behavior studies
  • Other issues, as needed

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

  • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for SLC9A6-related syndrome should begin as early as possible, ideally before a child begins school.

If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/…t-is-epilepsy/seizure-types

This section includes a summary of information from major published articles. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and references section of this guide.

Females have two X chromosomes and two copies of the SLC9A6 gene. Females carrying a pathogenic or likely pathogenic SLC9A6 variant sometimes have medical features.

Usually, the X chromosome carrying the variant undergoes selective X inactivation. This is a random process where a cell chooses one X chromosome to silence gene expression. If the affected X chromosome is inactivated, this means that the SLC9A6 variant would be silenced or turned off. For some females, the unaffected X chromosome is inactivated, resulting in a person having more medical features.

Female carriers might have learning difficulties, speech and language delay, mild-to-moderate intellectual disability, and behavioral issues.

The information below includes males with SLC9A6-related syndrome.

Speech and Learning

People with SLC9A6-related syndrome had developmental delay or intellectual disability and absent speech.

  • 95 out of 95 people had developmental delay or intellectual disability (100 percent)
  • 77 out of 83 people had absent speech (93 percent)

Behavior

Behavioral disorders occurred in people with SLC9A6-related syndrome, including features of autism.

  • 35 out of 47 people had features of autism (75 percent)

Brain

Most people with SLC9A6-related syndrome had seizures, with an age of onset under 2 years old. People developed seizures as young as 1 day old and as old as 4 years old. Seizure types varied and included myoclonic, generalized tonic–clonic, complex partial seizure, and absence seizures. About 1 in 3 people had cerebellar atrophy on magnetic resonance imaging (MRI).

No one type of anti-seizure medication worked for everyone with SLC9A6-related syndrome. Treatment was based on the seizure type and adjusted based on the effects. Some people were on a ketogenic diet to treat seizures.

  • 87 out of 88 people had seizures (99 percent)
  • 61 out of 77 people had microcephaly (79 percent)
  • 20 out of 57 people had cerebellar atrophy on MRI (35 percent)
99%
87 out of 88 people had seizures.
79%
61 out of 77 people had microcephaly.
35%
20 out of 57 people had cerebellar atrophy on MRI.

Developmental regression was reported in about one-half of people with SLC9A6-related syndrome.

Vision and hearing

About 3 out of 4 people had paralysis of the eye muscles, and most people had normal hearing.

  • 35 out of 49 people had paralysis of the eye muscles (71 percent)
  • 75 out of 83 people had normal hearing (90 percent)

Movement

Most people had movement difficulties, including but not limited to hyperkinesia (a state of restlessness). Eighteen adult males studied had progressive motor deterioration and ataxia (poor muscle control that causes clumsy movements), beginning in their 40s or 50s.

  • 40 out of 56 people had a movement disorder called hyperkinesia (71 percent)
  • 49 out of 63 people had a movement disorder called ataxia (78 percent)
71%
40 out of 56 people had a movement disorder called hyperkinesia.
78%
49 out of 63 people had a movement disorder called ataxia.

Other medical features

About one-half of people had sleep issues, and high pain tolerance was very common.

  • 17 out of 35 people had sleep issues (49 percent)

Where can I find support and resources?

Geisinger Developmental Brain Disorder Gene Database

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

Sources and References

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