GENE GUIDE

FOXP1-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 FOXP1-Related Syndrome.
a doctor sees a patient

FOXP1-related syndrome is also called FOXP1 haploinsufficiency or FOXP1-related neurodevelopmental disorder. For this webpage, we will be using the name FOXP1-related syndrome to encompass the wide range of variants observed in the people identified.

FOXP1-related syndrome happens when there are changes to the FOXP1 gene. These changes can keep the gene from working as it should.

Key Role

The FOXP1 gene is important in the development of the brain and body. It plays a key role in areas of the brain that control language.

The FOXP1 gene can also affect the development of other body parts, including the heart, ears, eyes, and genitals. FOXP1-related syndrome can have mild to moderate effects on the development of communication and social and learning skills. It can affect how a person acts or interacts with others.

Symptoms

Because the FOXP1 gene is important in the development and function of brain cells, many people who have FOXP1-related syndrome have:

  • Delayed development and/or intellectual disability
  • Speech and language delay
  • Autism spectrum disorder or features of autism
  • Other behavioral issues like ADHD and anxiety
  • Low muscle tone
  • Hypertonia and/or muscle spasms
  • Genitourinary issues
  • Heart issues
  • Eye issues
  • Gastrointestinal issues
  • Hearing issues
  • Feeding issues
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Seizures

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the FOXP1 gene: one copy from their mother, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new change. The child can be the first in the family to have the genetic change.

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because FOXP1 plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that FOXP1-related syndrome is often the result of a de novo change in FOXP1. Many parents who have had their genes tested do not have the FOXP1 gene change found in their child who has the syndrome. In some cases, FOXP1-related syndrome happens because the gene change was passed down from a parent.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

No parent causes their child’s FOXP1-related syndrome. We know this because no parent has any control over the genetic 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 genetic change took place on its own and could not have been 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 FOXP1-related syndrome depends on the genes of both birth parents.

  • If neither birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is on average 1 percent. This chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has FOXP1-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

  • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has FOXP1- related syndrome.
  • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom- free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has FOXP1-related syndrome is 50 percent.

For a person who has FOXP1-related syndrome, their risk of having a child who has the syndrome is 50 percent.

As of 2024, 200 people with FOXP1-related syndrome have been identified in medical research. The first case of FOXP1-related syndrome was described in 2009.

People who have FOXP1-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Larger than average head size
  • Wide-set eyes
  • Large lips

Scientists and doctors have only just begun to study FOXP1-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) for school.

Specialists advise that therapies for FOXP1-related syndrome should begin as early as possible, ideally before a child begins school.

This section includes a summary of information from major published studies. It highlights how many people have different symptoms.

To learn more about the articles, see the Sources and references section of this guide.

Speech and Learning

Almost all people with FOXP1-related syndrome had intellectual disability or developmental delay. Mild to moderate intellectual disability was present in 63 percent of people, whereas severe intellectual disability was present in 33 percent of people. All people had speech delays. Many people had problems making sounds and forming particular speech sounds properly, also called articulation issues.

  • 55 out of 61 people had intellectual disability or developmental delay (90 percent)
  • 60 out of 60 people had speech delay (100 percent)
  • 32 out of 48 people had articulation issues (67 percent)
90%
55 out of 61 people had intellectual disability or developmental delay.
100%
60 out of 60 people had speech delay.
67%
32 out of 48 people had articulation issues.

Behavior

Some people had autism or features of autism, and most had repetitive behaviors. Many people had psychiatric issues, including attention deficit hyperactivity disorder (ADHD), anxiety, or obssesive compulsive traits.

  • 28 out of 56 people had autism (50 percent)
  • 32 out of 56 people had psychiatric issues (57 percent)

Brain

About one-half of people with FOXP1-related syndrome had changes in their brain structure. Some findings included: white matter defects, cysts, and changes in the cerebellum or corpus callosum. Seizures in people with FOXP1-related syndrome did not have a specific pattern, and the age of onset was variable.

  • 29 out of 58 people had brain changes on MRI (50 percent)
  • 7 out of 59 people had seizures (12 percent)

Mobility

People who have FOXP1-related syndrome were usually late in developing skills, such as sitting and walking. Most started walking by themselves between the ages of 2 and 3 years. Some people had low muscle tone and were described as floppy, whereas others had higher than average muscle tone. Some had extremely flexible joints.

  • 18 out of 62 people had low muscle tone (29 percent)
  • 20 out of 58 people had higher than average muscle tone (34 percent)
  • 16 out of 56 people had a tightening of the muscles (29 percent)
  • 9 out of 62 people had difficulty walking (15 percent)
29%
18 out of 62 people had low muscle tone.
34%
20 out of 58 people had higher than average muscle tone.
29%
16 out of 56 people had a tightening of the muscles.
15%
9 out of 62 people had difficulty walking.

Feeding and Gastrointestinal

Constipation and gastroesophageal reflux disease (GERD) were common in people with FOXP1-related syndrome. One out of four people with FOXP1-related syndrome had feeding issues, like difficulty latching, in infancy. Most children were able to gain weight and grow well.

Heart

Almost one out of three people with FOXP1-related syndrome had cardiac issues, most commonly a hole in the heart (atrial septal defect). Less common defects included:  a narrowed heart valve (pulmonic stenosis), an opening between two blood vessels leading from the heart (patent ductus arteriosus), and a hole between the left and right upper chambers of the heart (patent foramen ovale).

  • 17 out of 56 people had cardiac issues (30 percent)

Genitourinary

Some people had genital or urinary formation issues.

  • 9 out of 41 males had undescended testicles (22 percent)
  • 3 out of 41 males had a diagnosis of micropenis (7 percent)
  • 3 out of 46 people had a horseshoe kidney (7 percent)

Vision and hearing

About one-half of people had vision issues, and some had issues with hearing or frequent ear infections.

  • 29 out of 58 people had vision issues (50 percent)
  • 11 out of 60 people had crossed eyes (18 percent)
  • 8 out of 48 people had hearing loss (17 percent)
  • 7 out of 60 people had recurrent ear infections (12 percent)
50%
29 out of 58 people had vision issues.
18%
11 out of 60 people had crossed eyes.
17%
8 out of 48 people had hearing loss.
12%
7 out of 60 people had recurrent ear infections.

Where can I find support and resources?

International FOXP1 Foundation

The International FOXP1 Foundation is a registered non-profit organization that is managed and staffed by parent volunteers. They are committed to supporting those who have been impacted by a FOXP1 diagnosis and to establishing regular venues for fundraising in an effort to further research into FOXP1 syndrome and possible treatments.

Friends and Family of FOXP1 Facebook Group

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 FOXP1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Le Fevre AK. et al. American Journal of Medical Genetics Part A, 161a, 3166-3175, (2013). FOXP1 mutations cause intellectual disability and a recognizable phenotype www.ncbi.nlm.nih.gov/pubmed/?term=24214399
  • Palumbo O. et al. Gene, 516, 107-113, (2013). 3p14.1 de novo microdeletion involving the FOXP1 gene in an adult patient with autism, severe speech delay and deficit of motor coordination www.ncbi.nlm.nih.gov/pubmed/?term=23287644
  • Lozano R. et al. European Journal of Human Genetics, 23, 1702-1707, (2015). A de novo FOXP1 variant in a patient with autism, intellectual disability and severe speech and language impairment www.ncbi.nlm.nih.gov/pubmed/?term=25853299
  • Song H. et al. Clinical Case Reports, 3, 110-113, (2015). A case report of de novo missense FOXP1 mutation in a non-Caucasian patient with global developmental delay and severe speech impairment www.ncbi.nlm.nih.gov/pubmed/?term=25767709
  • Sollis E. et al. Human Molecular Genetics, 25, 546-557, (2016). Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder www.ncbi.nlm.nih.gov/pubmed/?term=26647308
  • Bekheirnia MR. et al. Genetics in Medicine: Official Journal of the American College of Medical Genetics, 19, 412-420, (2017). Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene www.ncbi.nlm.nih.gov/pubmed/27657687
  • Meerschaut I. et al. Journal of Medical Genetics, 54, 613-623, (2017). FOXP1-related intellectual disability syndrome: a recognisable entity www.ncbi.nlm.nih.gov/pubmed/28735298
  • Siper PM. et al. Molecular Autism, 8, 57, (2017). Prospective investigation of FOXP1 syndrome www.ncbi.nlm.nih.gov/pubmed/?term=29090079
  • Rappold, G., Siper, P., Kostic, A., Braden, R., Morgan, A., Koene, S., & Kolevzon, A. 2023 Sep 21. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK594825

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