GENE GUIDE

PTCHD1-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 in 2025. 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 PTCHD1-Related Syndrome.
a doctor sees a patient

PTCHD1-related syndrome happens when there are changes in the PTCHD1 gene. These changes can keep the gene from working as it should.

The PTCHD1 gene is located on the X chromosome. Chromosomes are structures in our cells that house our genes. Only males who carry the genetic variation have the condition.

PTCHD1-related syndrome can also happen when larger segments of DNA are deleted within the Xp22.11 region. In these instances, the disorder is called Xp22.11 deletion syndrome.

Key Role

The PTCHD1 gene plays a key role in brain development and the function of brain cells.

Symptoms

Because the PTCHD1 gene is important for brain activity, many people who have PTCHD1-related syndrome have:

  • Failure to thrive
  • Autism
  • Developmental delay
  • Intellectual disability
  • Larger than average head size, also called macrocephaly
  • Smaller than average head size, also called microcephaly
  • Low muscle tone, also called hypotonia
  • High muscle tone, also called hypertonia
  • Poor balance and gait defects
  • Behavioral issues, such as mood disorders, aggression, and impulsivity
  • Vision issues

PTCHD1-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 PTCHD1 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 PTCHD1-related syndrome. 

Biological females who have variants in this gene may or may not have symptoms of PTCHD1-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 PTCHD1-related syndrome is often the result of an inherited variant in PTCHD1. This means that PTCHD1-related syndrome happens because the genetic variant was passed down from a biological female parent. Biological females that carry the PTCHD1 variant usually do not have symptoms, but sometimes they might. 

Sometimes it results from a spontaneous variant in the PTCHD1 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

No parent causes their child’s PTCHD1-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 foreseen 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 PTCHD1-related syndrome depends on the genes of both biological parents. 

  • Biological females who have a variant in the PTCHD1 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 PTCHD1-related syndrome, the sibling’s risk of having a child who has PTCHD1-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing PTCHD1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit PTCHD1-related syndrome. 
  • If the biological mother has the same genetic variant causing PTCHD1-related syndrome, and the symptom-free daughter has the variant, the symptom-free daughter’s chance of having a son who has PTCHD1-related syndrome is 50 percent. 

For a person who has PTCHD1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, over 30 people with PTCHD1-related syndrome have been described in medical research. This includes people with pathogenic or likely pathogenic variants in the PTCHD1 gene and people with larger deletions that include the PTCHD1 gene.

People who have PTCHD1-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Long face
  • Forehead that sticks out
  • Puffy eyelids
  • Narrow face with a small chin
  • Noticeable upper central teeth
  • Depressed and narrowed nasal bridge with a broad nasal tip and upward tilting nostrils
  • Thin upper lip
  • Mouth that is open at rest

Scientists and doctors have only just begun to study PTCHD1-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 PTCHD1-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/learn/types-seizures.

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 PTCHD1 gene. Females who carry a pathogenic or likely pathogenic PTCHD1 variant rarely 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 PTCHD1 variant would be silenced or turned off. For some females, the unaffected X chromosome is inactivated, resulting in a person having more medical features.

The information below includes 27 males and 1 female with PTCHD1-related syndrome. Most female carriers do not have medical features.

Learning

The majority of people with PTCHD1-related syndrome had global developmental delay or intellectual disabilities, ranging from mild to severe. People had speech delays.

  • 24 out of 28 people had global developmental delay or intellectual disability (86 percent)

Behavior

Less than one-half of people with PTCHD1-related syndrome had autism. One-quarter had behavioral issues, such as mood disorders and hyper-aggression.

  • 12 out of 28 people had autism spectrum disorder or features of autism (43 percent)
  • 7 out of 28 people had other behavioral issues, such as mood disorders, hyperactivity, or aggression (25 percent)
43%
12 out of 28 people had autism spectrum disorder or features of autism.
25%
7 out of 28 people had other behavioral issues, such as mood disorders, hyperactivity, or aggression.

Brain

People with PTCHD1-related syndrome had low muscle tone (hypotonia) or high muscle tone (hypertonia). Many people had low muscle tone in their facial muscles. Some people with PTCHD1-related syndrome had a smaller than average head size (microcephaly) or a larger than average head size (macrocephaly). Some people had sleep difficulty.

  • 6 out of 23 people had hypotonia (26 percent)
  • 2 out of 23 people had mild hypertonia (9 percent)
  • 3 out of 23 people had microcephaly (13 percent)
  • 4 out of 23 people had macrocephaly (18 percent)
Human head showing brain outline
26%
6 out of 23 people had hypotonia.
9%
2 out of 23 people had mild hypertonia.
13%
3 out of 23 people had microcephaly.
18%
4 out of 23 people had macrocephaly.

Growth

Few people with PTCHD1-related syndrome had growth issues like early failure to thrive.

  • 2 out of 23 people had early failure to thrive (9 percent)

Mobility

Sometimes people with PTCHD1-related syndrome had mobility issues like poor balance and gait defects.

  • 6 out of 28 people had poor balance and gait defects (21 percent)

Vision

Some people with PTCHD1-related syndrome had mild vision problems, including crossed eyes (strabismus), jerky eye movements, cataracts, an imperfection of the eye that causes blurred distance and near vision (astigmatism), and nearsightedness (myopia).

  • 8 out of 23 people had vision issues (35 percent)

Where can I find support and resources?

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

The content in this guide comes from published studies about PTCHD1-related syndrome.

  • Chaudhry, A., Noor, A., Degagne, B., Baker, K., Bok, L. A., Brady, A. F., Chitayat, D., Chung, B. H., Cytrynbaum, C., … & Carter, M. T. (2015). Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder. Clinical Genetics, 88(3), 224-233. https://pubmed.ncbi.nlm.nih.gov/25131214/
  • Filges, I., Röthlisberger, B., Blattner, A., Boesch, N., Demougin, P., Wenzel, F., Huber, A. R., Heinimann, K., Weber, P., & Miny, P. (2011). Deletion in XP22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism. Clinical Genetics, 79(1), 79-85. https://pubmed.ncbi.nlm.nih.gov/21091464/
  • Montanaro, F. A. M., Mandarino, A., Alesi, V., Schwartz, C., Sepulveda, D. J. C., Skinner, C., Friez, M., Piccolo, G., Novelli, A., … & Alfieri, P. (2024). PTCHD1 gene mutation/deletion: The cognitive-behavioral phenotyping of four case reports. Frontiers in Psychiatry, 14, 1327802. doi:10.3389/fpsyt.2023.1327802 [correction: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1375954/full]
  • Pastore, S. F., Ko, S. Y., Frankland, P. W., Hamel, P. A., & Vincent, J. B. (2022). PTCHD1: Identification and neurodevelopmental contributions of an autism spectrum disorder and intellectual disability susceptibility gene. Genes (Basel), 13(3). 527. https://pubmed.ncbi.nlm.nih.gov/35328080/

Stay connected with Simons Searchlight

Join our newsletter to receive updates