SETD5 Syndrome Foundation

Funding the Science.
Empowering the Families.

We are a family-led nonprofit dedicated to accelerating research into SETD5 Syndrome, a rare genetic condition, while building a global community of support, hope, and action.

Donate Now Learn About SETD5 Syndrome

Our Impact So Far

300+ Known Families
12 Active Research Projects
$1.2M Research Funded
18 Countries Represented

"Every dollar brings us closer to answers."

<1,000 Known Cases Worldwide
2013 Gene First Identified
$1.2M+ Research Funded
100% Family-Led Mission
Children with SETD5 Syndrome
What is SETD5 Syndrome?

A Rare Genetic Condition with a Growing Community

SETD5 Syndrome is caused by changes (variants or deletions) in the SETD5 gene. This gene plays a critical role in brain development, and when it doesn't work as expected, it can affect many areas of development. Common features include intellectual disability, autism spectrum disorder, speech and language delays, and behavioral differences such as attention and hyperactivity challenges. SETD5 Syndrome can also lead to a range of physical symptoms, which vary from person to person.

Most cases arise spontaneously (de novo), meaning there is no prior family history. However, SETD5 Syndrome follows an autosomal dominant inheritance pattern, so in some families an affected parent can pass the variant to a child. SETD5 Syndrome was first described in 2014, and the global community of diagnosed individuals is still growing as genetic testing becomes more widespread.

Every person with SETD5 Syndrome is unique. This is a condition of beautiful complexity, and our mission is to fully understand it and support those living with it.

Learn More About the Condition
Research Highlights

Science Funded by Families, For Families

Your donations directly fund breakthrough research. Here is a snapshot of what is currently underway.

Basic Science

SETD5 Protein Function in Neural Development

Researchers are mapping exactly how the SETD5 protein regulates gene expression in developing brain cells, the essential first step toward targeted therapies.

Stanford University · Active
Natural History

Global SETD5 Patient Registry & Natural History Study

A first-of-its-kind longitudinal registry tracking development, health, and quality of life across hundreds of individuals with SETD5 Syndrome worldwide.

Vanderbilt University · Active
Therapeutics

Drug Screening in SETD5 Mouse Models

Using validated animal models, scientists are testing candidate compounds that may restore some SETD5 function, a critical step toward clinical trials.

Baylor College of Medicine · Active
View All Research Projects
Family Stories

The Faces Behind Our Mission

SETD5 Syndrome Foundation was built by parents who refused to wait. Here is why we do this work.

"When our daughter was diagnosed at age three, we found other families online, we connected with researchers, and we realized: if we didn't build this foundation, no one would. Every dollar raised is a message to our kids: we see you, we believe in you, and we will not stop."
JD
Jane D.
Co-Founder, SETD5 Syndrome Foundation · Parent of a child with SETD5 Syndrome
Our Full Story

Every Gift Funds a Breakthrough

Research doesn't wait. Neither do our families. A donation today keeps scientists at the bench and gives hope to hundreds of families around the world.

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Understanding the Condition

About SETD5 Syndrome

Plain-language information about the genetics, symptoms, diagnosis, and daily life with SETD5 Syndrome, written for families first.

The Basics

What Is SETD5 Syndrome?

SETD5 Syndrome (also called MRD23, or Mental Retardation, Autosomal Dominant 23) is a rare neurodevelopmental condition caused by changes in the SETD5 gene, located on chromosome 3p25.3.

The SETD5 gene provides instructions for making a protein that helps regulate which genes are turned on or off during brain development. When one copy of this gene has a variant or is partially deleted, the protein may not function properly, which can affect how the brain develops.

SETD5 Syndrome typically occurs as a de novo (new, spontaneous) change, meaning most affected individuals are the first in their family to carry it. It is not usually inherited from a parent, though familial cases are documented.

It is estimated to affect fewer than 1,000 people worldwide, though the true prevalence is likely higher, as many individuals remain undiagnosed.

Quick Facts

Gene: SETD5 (SET Domain Containing 5)
Chromosome: 3p25.3
Inheritance: Autosomal dominant; usually de novo
First described: 2014 (Grozeva et al.)
Estimated prevalence: fewer than 1,000 known cases worldwide
Diagnosis: Chromosomal microarray or whole-exome/genome sequencing
SETD5 Syndrome is a diagnosis, not a destiny. Every child is unique, and every family's journey looks different.
Signs & Symptoms

What Does SETD5 Syndrome Look Like?

SETD5 Syndrome presents differently in every person. Some individuals have mild features, while others may have more significant support needs. No two individuals are exactly alike.

Intellectual Disability

Ranging from mild to moderate; affects learning and adaptive skills.

Speech & Language Delays

Expressive language is often more affected than understanding. Many children are minimally verbal early on.

Autism Spectrum Features

Social communication differences, repetitive behaviors, and sensory sensitivities are common.

Behavioral Differences

Hyperactivity, impulsivity, ADHD-like features, and sometimes anxiety or mood dysregulation.

Hypotonia (Low Muscle Tone)

Often present in infancy; can affect feeding, motor milestones, and gross motor skills.

Gross & Fine Motor Delays

Walking may be delayed; coordination challenges are common. Most children do walk independently.

Mild Facial Features

Some individuals have subtle facial differences including widely spaced eyes, a broad forehead, or a prominent chin.

Epilepsy

Occurs in a subset of individuals. Seizure types vary and are typically managed with medication.

Important: This information is for educational purposes only and does not constitute medical advice. Every individual with SETD5 Syndrome is unique. Please consult with a qualified genetics specialist or developmental pediatrician for personalized guidance.

The Diagnostic Journey

From "Something Is Different" to a Diagnosis

Many families travel a long road before receiving a diagnosis of SETD5 Syndrome. Understanding this journey can help families advocate effectively.

1

Developmental Concerns Are Noticed

Parents or a pediatrician notice developmental delays (often in speech, motor skills, or social development), typically in the first 1-3 years of life.

2

Referral to Specialists

A referral to a developmental pediatrician, neurologist, or geneticist follows. Initial testing (MRI, metabolic panels) may be inconclusive.

3

Genetic Testing

Chromosomal microarray (CMA) or whole-exome sequencing (WES) is ordered. This is the testing that identifies SETD5 variants or deletions.

4

Diagnosis Confirmed

A pathogenic or likely pathogenic SETD5 variant is identified. Parents receive a formal diagnosis, often a moment of grief and relief at once.

5

Finding Community

Connecting with SETD5 Syndrome Foundation and other families is one of the most powerful steps after diagnosis. You are not alone.

Frequently Asked Questions

Questions Families Often Ask

Could I have passed this on to my child? +
In most cases, SETD5 Syndrome arises as a de novo (spontaneous, new) change; it was not inherited from either parent. Parents' genetic testing is typically normal. However, in rare cases, a parent may carry a variant with variable expressivity. A genetics counselor can review your family's specific situation.
Will my child walk and talk? +
Most children with SETD5 Syndrome do learn to walk, though it may be delayed. Language outcomes vary significantly. Some individuals develop functional verbal communication, while others use augmentative and alternative communication (AAC). Early speech-language therapy makes a meaningful difference.
Is there a cure or treatment? +
There is currently no cure for SETD5 Syndrome, but researchers are actively working toward targeted therapies. In the meantime, individualized therapies (speech, occupational, physical, behavioral) significantly improve quality of life. This is exactly why research funding matters so much.
What is the recurrence risk for future pregnancies? +
Because most cases are de novo, the recurrence risk in future pregnancies is generally low (estimated around 1%). However, if a parent is found to carry the same variant, the risk increases to 50%. Genetic counseling and prenatal testing options are available.
How do I connect with other families? +
SETD5 Syndrome Foundation maintains a private family community where parents, caregivers, and self-advocates can connect, share, and support one another. Reach out through our Contact page to be connected.

Newly Diagnosed? You Are Not Alone.

We connect families with resources, community, and the latest research. Reach out; we respond to every message.

Contact the Foundation
Research & Science

Funding the Science of SETD5 Syndrome

Every dollar raised goes directly toward understanding SETD5 Syndrome and, ultimately, finding treatments. Here is the work your generosity makes possible.

Our Research Mission

From Discovery to Treatment

SETD5 Syndrome was only first described in scientific literature in 2014. The field is young, which means there is enormous potential for rapid progress with the right investment.

Our foundation funds research across the full pipeline: from understanding the basic biology of SETD5, to modeling the condition in animal systems, to developing and testing candidate therapies. We work closely with our Scientific Advisory Board to ensure every funded project is rigorous, collaborative, and moves us closer to helping families.

We are also committed to family-centered research, which means patients and families have a voice in setting research priorities.

12
Active Projects
$1.2M+
Funded to Date
8
Institutions
24
Publications
Current Research

Funded Research Projects

These projects represent the cutting edge of SETD5 Syndrome science, made possible by families like yours.

Basic Science Active

SETD5 Protein Function in Neural Development

Mapping the molecular role of the SETD5 protein in transcriptional regulation during early brain development, identifying downstream targets.

PI: Dr. A. Chen
Institution: Stanford
Since: 2022
Natural History Active

Global Patient Registry & Natural History Study

Longitudinal tracking of development, health outcomes, and quality of life in individuals with SETD5 Syndrome across 18+ countries.

PI: Dr. M. Patel
Institution: Vanderbilt
Since: 2021
Therapeutics Active

Drug Screening in SETD5 Mouse Models

High-throughput screening of FDA-approved compounds and novel molecules that may rescue SETD5-associated phenotypes in validated mouse models.

PI: Dr. J. Williams
Institution: Baylor
Since: 2023
Genomics Active

Genotype-Phenotype Correlation Analysis

Analyzing whether the type or location of SETD5 variant (missense vs. truncating vs. deletion) predicts clinical severity or specific features.

PI: Dr. L. Nguyen
Institution: NIH
Since: 2022
iPSC Modeling Active

Human iPSC-Derived Neuronal Models

Creating patient-derived stem cell lines and differentiating them into neurons to study SETD5 Syndrome in human cell systems for drug testing.

PI: Dr. R. Torres
Institution: UCSF
Since: 2023
Clinical Planning

Behavioral Intervention Study

A prospective study examining the effectiveness of tailored behavioral and communication interventions in children with SETD5 Syndrome ages 2-8.

PI: TBD
Institution: Boston Children's
Since: 2025
Research Milestones

How Far We Have Come

The SETD5 Syndrome field has progressed rapidly in a short time. Here is the story of that progress.

2013

SETD5 Gene First Associated with Intellectual Disability

Researchers first identify SETD5 variants in individuals with unexplained intellectual disability.

2014

SETD5 Syndrome Formally Described

Grozeva et al. publish the first paper formally characterizing SETD5 haploinsufficiency as a distinct syndrome.

2017

First Family Support Group Formed on Facebook

Families from around the world connect for the first time, forming the community that would become the foundation of this organization.

2018

First Mouse Model Validated

A heterozygous Setd5 mouse model is validated, recapitulating key behavioral and neurological features of the human condition.

2026

SETD5 Syndrome Foundation Formed

Families launch the foundation to accelerate research and provide community support to a growing global patient population.

Scientific Advisory Board

Our Scientific Leadership

Our SAB comprises leading scientists in neurodevelopmental genetics, epigenomics, and rare disease therapeutics who guide our research strategy.

AC

Dr. Amy Chen, PhD

SAB Chair
Stanford University
MP

Dr. Mark Patel, MD

Clinical Lead
Vanderbilt University
JW

Dr. Jane Williams, PhD

Therapeutics
Baylor College of Medicine
RT

Dr. Rafael Torres, MD

iPSC Modeling
UCSF

Interested in Collaborating?

We welcome inquiries from researchers interested in SETD5 Syndrome. Contact our research team to explore funding and collaboration opportunities.

Get in Touch

Fund the Next Breakthrough

Our next round of research grants opens soon. Your gift today helps us say "yes" to the science that matters most.

Donate to Research
Our Team

A Foundation Built by Families

We started as a handful of parents with no roadmap. Today we are a growing global foundation with a clear mission: find answers for our children.

Our Story

How We Got Here

When our children were diagnosed with SETD5 Syndrome, we received a name but little else. There was no patient registry, no foundation, no family community to speak of. Research was scattered, slow, and underfunded.

"We could not wait for someone else to build what our children needed. So we built it ourselves."

In 2021, a group of parents from the United States, Europe, and Australia came together with a single conviction: that a rare disease this newly understood could move from mystery to treatment faster than anyone thought possible, if families organized, raised money, and partnered directly with science.

We hired no executives. We kept our overhead low. We put every dollar toward research and families. And we built the SETD5 Syndrome Foundation.

Today, we fund 12 active research projects, support hundreds of families across 18 countries, and have helped produce 24 peer-reviewed publications on SETD5 Syndrome. We are just getting started.

Mission, Vision & Values

What We Stand For

Our Mission

To accelerate research into SETD5 Syndrome and support the global community of individuals, families, and clinicians affected by this rare genetic condition.

Our Vision

A world where every person with SETD5 Syndrome has access to effective treatments, early diagnosis, and a thriving community of support.

Science First

We fund rigorous, peer-reviewed research guided by our Scientific Advisory Board.

Family-Led

Every decision is made with the lived experience of families at the center.

Global & Inclusive

SETD5 Syndrome affects families everywhere. Our community has no borders.

Leadership

Board of Directors

Our board is entirely composed of parents, caregivers, and allies who volunteer their time, skills, and passion to this mission.

MR

Michael R.

Board Member
Parent of a child with SETD5 Syndrome. CPA with 20 years of nonprofit finance experience.
LT

Lisa T.

Board Member
Pediatric occupational therapist and parent advocate. Leads our family support programming.
Jane D.

Jane D.

Board Member
Parent, runs her own nonprofit, and built this website.
DM

David M.

Board Member
Technology executive and parent. Oversees our digital infrastructure and communications strategy.
Reach Out

We Would Love to Hear From You

Whether you are newly diagnosed, a researcher, a donor, or a journalist, we respond to every message.

General Inquiries info@setd5foundation.org
Research & Grants research@setd5foundation.org

Send Us a Message