3q29 Duplication Syndrome: An In-Depth Description of What’s Known to Date

3q29 duplication syndrome (3q29Dup) is a rare genetic condition that occurs when a small region of the third chromosome is duplicated. Not much is known about how it affects those who have it. It seems to go undetected in some people while presenting significant problems in others.

Before this study, there were only a few case reports describing the possible effects of 3q29Dup. Some of the observed effects included developmental delay, speech delay, seizures, behavioral issues, and problems with the eyes, heart, and/or teeth. 

Researchers with the 3q29 Project wanted to have a better understanding of this condition. They developed a study with three goals:

  1. Determine if people with 3q29Dup have high rates of neuropsychiatric diagnosis and social disability found with 3q29 deletion syndrome

  2. Learn more about how this small section of the 3q29 chromosome affects organ systems and brain development

  3. Analyze enough information to make evidence-based recommendations on clinical care

Through an Internet-based registry, The 3q29 Project collected information about people with 3q29Dup. While the sample size was small, it was the largest group studied to date. 

You can read the full study here or continue reading the overview below. 

About the Study

To achieve the goals of the study, researchers focused on the following points:

  • What medical problems, if any, are common among people with 3q29Dup?

  • What neuropsychiatric problems, if any, are common among this group?

  • How do the medical and/or neuropsychiatric problems compare to those seen with 3q29 deletion syndrome?

Thirty-one participants with 3q29Dup were recruited and information was collected and analyzed through the 3q29 registry. The data was compared to that of 117 participants with 3q29 deletion syndrome and 64 controls (people who represent the general population). 

Participants or their caregivers/parents were given a custom questionnaire asking about 7 areas of physical and mental development: 1) birth history 2) development 3) ear/nose/throat 4) gastrointestinal 5) renal 6) oral/dental and 7) history of seizures/psychiatric issues. 

Then, two standardized questionnaires—the Social Responsiveness Scale (SRS) and the Child Behavior Checklist (CBCL) / Adult Behavior Checklist (ABCL)—were used to assess general behavior and symptoms related to autism spectrum disorder (ASD). 

The SRS provides an overall score indicating “social ability” and also scores on several sub-scales. These sub-scales examine specific areas of social functioning in the areas of:

  • Social Awareness

  • Social Cognition

  • Social Communication

  • Social Motivation

  • Restricted Interests and Repetitive Behaviors

  • Social Communication and Interaction

What the Study Found

After collecting and analyzing data, some patterns emerged. Those with 3q29Dup were more likely to have certain medical and neuropsychiatric issues compared to the control group. 

The 3q29Dup group had some similarities to the 3q29Del group and also some differences. 

Medical and Developmental Issues: 3q29Dup vs Controls

Problems at birth. Compared to the general population, the data indicated people with 3q29Dup are more likely to experience medical issues from birth. 


For example, they tend to have lower weight at birth, spend longer in the hospital (9.8 days on average compared to 3.8 days for controls), and report significant health problems in the first year of life (80.6% compared to 39.1% for controls). 

The most common reasons cited for the lengthier hospital stays and the need for more medical care in the first year of life were feeding difficulties, failure to gain weight, hypotonia, and respiratory distress.

Early childhood. Beyond the first year of life, the study found that about 55% of participants reported at least one gastrointestinal problem including feeding difficulties and chronic constipation. Before this study, gastrointestinal and feeding problems were not associated with 3q29Dup.

Developmental delays such as smiling, first word, walking, and drinking from an open cup were common in early childhood. Social-emotional, gross motor, and fine motor milestones were delayed on average by 10 months, 15 months, and 16 months, respectively. Communication milestones were more considerable and delayed by an average of 25 months.

Seizures. This study confirmed prior reports of a higher rate of seizures among 3q29Dup participants than in the general population. 

Medical complications reported by 3q29Dup participants:

  • Medical problems at birth (80.6%)

    • Feeding difficulties (58.4%)

    • Failure to gain weight (41.9%)

    • Hypotonia, or low muscle tone (38.7%)

    • Respiratory distress (29%)

  • Gastrointestinal issues (55%)

    • Feeding difficulties beyond the first year of life (38.7%)

    • Chronic constipation (35.5%)

  • Seizures (25.5%)

  • Heart defects (6%)

  • Genitourinary issues (6%)

  • Renal problems (16%)

  • Ear problems (42%)

  • Dental problems (68%)

Neurodevelopmental and Psychiatric Findings: 3q29Dup vs Controls

Learning. Prior reports and case studies point to an increase in mild to moderate intellectual disability among those identified with 3q29Dup. The participants in this study were also much more likely to have a diagnosed learning problem than controls (87.1% vs 4.7%). 

Commonly reported learning issues and their prevalence among the participants included:

  • Expressive language delay (41.9%)

  • Receptive language delay (29%)

  • Learning disability in math (25.8%)

  • Learning disability in reading (25.8%)

Neuropsychiatric. The 3q29Dup study participants reported higher rates of neuropsychiatric diagnoses (32.3%) than is expected to be found in the general population (5.7%). 

  • ASD (38.7% which is higher than previously reported among the 3q29Dup population)

  • Conduct disorder (6.5%)

  • Depression (16.1%)

  • Oppositional defiant disorder (6.5%)

  • Panic attacks (6.5%)

Social and behavioral. The researchers then looked closely at the social skills of the 3q29Dup participants. The Social Responsiveness Scale (SRS) was used. The higher the score, the more “social impairment” was present.

Overall SRS scores among the 3q29Dup population were significantly higher (indicating a greater degree of disability) than those of typically developing controls, regardless of sex or ASD diagnosis. This overall score is helpful, but how the participants performed on the sub-scales provided insight into specific areas of social strengths and weaknesses. 

On average, the 3q29Dup study group showed the most severe impairment in the areas of:

  • Social Communication

  • Restricted Interests and Repetitive Behaviors

  • Social Communication and Interaction 

Impairment fell within the moderate range in the areas of:

  • Social Awareness

  • Social Cognition

  • Social Motivation

Researchers also noted:

  • Of all the domains, participants with 3q29Dup performed best on the Social Motivation sub-scale. 

  • 3q29Dup participants with a reported ASD diagnosis showed a greater impairment on every sub-scale than those without an ASD diagnosis. However, the 3q29Dup group with ASD had better Social Motivation scores than controls with idiopathic ASD.

  • While males and females scored about the same, females did slightly better in all areas except Social Awareness. (The sample size wasn’t big enough to make any firm conclusions on this but this would be interesting to revisit in future studies.) 

  • Those with 3q29Dup were more likely to show signs of ADHD, depression, and anxiety.

3q29 Duplication vs 3q29 Deletion

This study compiled lots of new information about 3q29 duplication syndrome. Researchers then compared these new findings to what was already known about 3q29 deletion syndrome. Discovering similarities and differences would help scientists understand more about this area of the 3q29 chromosome. 

Medical similarities and differences between 3q29Dup and 3q29Del:

  • Congenital heart defects are reported at a significantly higher rate by 3q29Del participants as compared to 3q29Dup participants (24.8% vs. 6.5%).

  • 3q29Dup participants reported greater rates of seizures than 3q29Del participants (25.8% vs. 15.4%). 

  • Genitourinary problems are reported twice as often among the 3q29Del group as compared to the 3q29Dup group (12.8% vs. 6.5%). 

  • While both groups had low weight at birth, obesity has been noted among the 3q29Dup population whereas low weight persists throughout adolescence among the 3q29Del population.

  • Rates of all other reported medical problems are similar between the two groups.

Psychiatric and social similarities and differences between 3q29Dup and 3q29Del:

  • 3q29Dup participants and 3q29Del participants had similar scores on the CBCL/ABCL test. This means both groups are equally prone to ADHD, anxiety, and depression.

  • The rate of reported ASD was higher among the 3q29Dup group, but this number was not statistically significant. It’s an area to investigate further. 

  • The way ASD and social impairment looked among the two groups were similar. 

  • The rates of each psychiatric disorder vary between the groups.

What It Means

As a result of this study, researchers have a better idea of what medical and developmental issues can occur with 3q29Dup. This means specific recommendations can be now made about care and intervention:

The problems associated with 3q29Dup at birth suggest babies should receive extra medical attention during infancy. It’s also recommended that children be evaluated by a pediatric neurologist to assess the potential for seizures, and a pediatric gastroenterologist to address feeding problems and constipation. Finally, people with 3q29Dup should be assessed for ASD and social disability. 

Even though this was the largest group of people with 3q29Dup ever studied to date, the sample size was still very small. This means some of the observations were noted but weren’t statistically significant. 

Researchers also acknowledge that the participants in this study may represent those who are more severely affected. 3q29Dup can go completely undetected, so the people in this study likely exhibited some signs that prompted genetic testing. 

Additionally, the participants and/or their families may not represent the general 3q29Dup population because they had to be motivated to complete online questionnaires and have the resources and time to travel to Atlanta, GA.