PPP2R1A-Related Syndrome

PPP2R1A-related syndrome happens when there are changes in the PPP2R1A gene. These changes can keep the gene from working as it should.

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 PPP2R1A-related syndrome depends on the genes of both biological parents. 

• If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent 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 genetic variant. 
• If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent. 

For a symptom-free brother or sister of someone who has PPP2R1A-related syndrome, the sibling’s risk of having a child who has PPP2R1A-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing PPP2R1A-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit PPP2R1A-related syndrome. 
• If one biological parent has the same genetic variant causing PPP2R1A-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has PPP2R1A-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 50 people with PPP2R1A-related syndrome have been identified in medical research.

People who have PPP2R1A-related syndrome may look different. Appearance can vary and can include some but not all of these features:

• Larger or smaller than average head size
• Longer face with a taller forehead
• Wide-set eyes
• Smaller than average opening of the eyelids
• A small nose with a noticeable nasal tip
• Thin upper lip
• Drooping eyelid

Scientists and doctors have only just begun to study PPP2R1A-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 PPP2R1A-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

Most people had intellectual disability, usually ranging from moderate to severe, and developmental delay, ranging from mild to profound. Most people had speech and language delay, with some people remaining non-verbal.

• 56 out of 57 people had intellectual disability (98 percent)
• 42 out of 42 people had developmental delay (100 percent)
• 39 out of 39 people had speech and language delay (100 percent)

Most people had delayed walking, and some people were unable to walk. Most people had low muscle tone, and some of those with low muscle tone had long-lasting or permanent low muscle tone.

• 28 out of 30 people had delayed walking (93 percent)
• 30 out of 36 people had motor delays (83 percent)
• 44 out of 50 people had low muscle tone or hypotonia (88 percent)

About one-half of people had seizures, which were often associated with moderate-severe intellectual disability. People with a small head size had an increased risk of developing seizures, and those who had seizures typically developed them in the first year of life. In a few people, seizures were multifocal and did not respond to medication. People with seizures were more likely to display behavioral issues like ADHD, anxiety, self-harm or destructive behavior, and autism. About two-thirds of people had brain changes seen on magnetic resonance imaging (MRI).

• 25 out of 50 people had seizures (50 percent)
• 18 out of 54 people had a large head size or macrocephaly (33 percent)
• 23 out of 54 people had a small head size or microcephaly (43 percent)
• 37 out of 55 people had corpus callosum hypoplasia (67 percent)
• 15 out of 38 people had an enlargement of the ventricles of the brain, also called ventriculomegaly (39 percent)
• 22 out of 27 people had behavior issues (81 percent)

Growth

Some people were shorter than average in height.

• 3 out of 37 people had short height (8 percent)

Other physical issues included: external ear formation issues; hearing loss; joint hypermobility; sideways curve of the spine, also called scoliosis; feeding difficulty; and heart issues.

• 11 out of 37 people had external ear formation issues (30 percent)
• 5 out of 38 people had hearing loss (13 percent)
• 14 out of 37 people had joint hypermobility (38 percent)
• 9 out of 37 people had scoliosis (24 percent)
• 23 out of 38 people had feeding difficulty (61 percent)
• 3 out of 37 people had persistent ductus arteriosus, an opening in the heart that usually goes away after birth (8 percent)

PPP2R5D Foundation Website

Jordan’s Guardians Angels’ mission is to conduct research seeking answers to rare genetic mutations affecting children and adults, and assist and improve the quality of life for children and families.

• JordansGuardianAngels.org

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.”

• Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions

• Simons Searchlight webpage with more information on PPP2R1A: www.simonssearchlight.org/research/what-we-study/ppp2r1a

• Simons Searchlight Community: https://www.facebook.com/groups/1095511794170880/