Alternate gene names: DUPLIN, KIAA1564
Associated syndromes or conditions: Susceptibility to autism type 18
Genomic location: 14q11.2
Diagnoses observed in people with changes in the CHD8 gene:
- Autism Spectrum Disorder – some (few)
- Intellectual Disability or Developmental Delay - Yes
- Epilepsy or Seizures - Yes
- Attention Deficit Hyperactivity Disorder – some (few)
- Schizophrenia – some (few)
- Bipolar Disorder - No
CHD8: Simons VIP Connect Community Simons VIP Connect Facebook Group for CHD8 Families
CHD8 Family Group Closed Facebook Group
In addition to the opportunity to participate in research with Simons VIP, you may be interested in other opportunties.
TIGER Study: The University of Washington’s Autism Center is performing a study to better understand the medical, learning, and behavioral features of individuals with changes in CHD8.
Click here to learn more about this opportunity.
Research Article Summaries:
We summarized several research articles about the CHD8 gene. We hope you find this information helpful. As we learn more from children who have these gene changes, we expect this list of resources and information to grow.
Stolerman et al., (2016) – CHD8 intragenic deletion associated with autism spectrum disorder
The work presented in this article provides further evidence that the changes in the CHD8 play a major role in Autism Spectrum Disorder (ASD). Studies aimed at characterizing the features of rare genetic changes that lead to articles like this one support how big of an impact families can have by contributing to research. Like Simons VIP, the research model presented in this article relies on families engaging in the research process to tell us what they have experienced with their genetic change. By doing things like filling out the Simons VIP surveys and providing feedback to us substantially helps in the process of better understanding genetic changes associated with features of ASD, and we thank families for their continued participation in the Simons VIP research as well as other studies like it.
In this article, the researchers describe the clinical features observed in a case study of one child with a genetic change (also called a mutation or variant) in the CHD8 gene – this child’s genetic mutation was not contributed from either parent (known as a de novo type of genetic change/mutation/variant). The investigators reviewed the medical history of the 9-year-old boy and generated a timeline, detailing concerns identified through his childhood. The clinicians completed an in-depth evaluation of the child, beginning at pregnancy through age 9.
The child’s prenatal history was typical- he was born at full term, there were no prenatal complications or major postnatal complications, and typical development behaviors (like making eye contact and interacting) continued until 9 months of age. At that time, the child stopped making good eye contact and became irritable, crying regularly. He also had delays in developmental milestones (For example, he did not sit until 9 months of age and did not begin walking until 18 months of age). An evaluation of his hearing at 23 months of age showed no abnormalities. At just over two years old, it was noted that his speech was not progressing with that of his peers and that he was having abnormal social interactions (including aggressive behavior, poor eye contact and repetitive behaviors). When he was 27 months of age, he was given an initial developmental evaluation in which the characteristics listed *below were noted (Common features of the CHD8 mutation, which were outlined in Bernier et al.’s 2014 study on the CHD8 gene, that were observed in this child included gastrointestinal issues, increased head size (called macrocephaly), and dysmorphic features, while his height, weight, and head circumference were all normal for his developmental age).
*Notable findings from the child’s developmental assessment at 2y 3mo
· Did not respond to his name
· Did not retrieve objects
· Failed to initiate interactions, imitate, or point to pictures or objects
· Was unable to distinguish his mother’s voice from others
· Had limited vocalizations of monotone sounds
· Was hyperactive and unable to keep his attention on or finish tasks or activities
· Was unable to follow one-step instructions
· Overly reactive to change and easily frustrated, over-stimulated
· Had temper tantrums when demanded to complete tasks; tantrums with screaming, kicking, biting, hitting, crying, pinching and hair pulling
· Ate and chewed on non-edible objects
· Unaware of potential dangers
· Showed repetitive behaviors such as lining things up, touching things in a specific pattern, and putting objects in the same spots
· Unable to understand or prompt social cues and did not relate to children his age
· Showed some enjoyment of attention from and interaction with his mother
· Showed some delays in motor skills
· Able to grasp items, to feed himself using his fingers, and to drink from a sippy cup
· Able to climb and run
Cognition and Learning Skills:
· Scored low percentile for many of these tests administered:
o Bayley Scales of Infant and Toddler Development
§ Cognitive score: 60
§ Language score: 47
o Vineland Adapted Behavior Scale
§ Composite score: 61
§ Communication score: 56
§ Daily Living Skills score: 67
§ Socialization score: 56
§ Motor Skills score: 74
· Overall, these tests demonstrated delays in cognitive, language, motor, and adaptive skills, with the following formal diagnoses:
o Autism Spectrum Disorder (ASD)
o Global developmental delay
o Disruptive behavior disorder
o Pica (eating disorder)
· History of the following:
o otitis media (ear infections)
o eosinophilic esophagitis
o gastroesophageal reflux
After diagnoses of his CHD8 genetic change, the boy began physical, speech, and occupational therapy sessions. Some improvements were seen by age 4 with the administration of medication and behavioral therapies. In addition to this case study, the authors also provide a comparison of this 9-year-old boy to 18 other cases of children and adults with CHD8 mutations – the table below lists the features seen in each of those 19 patients.
Bernier et al., 2014 - Disruptive CHD8 Mutations Define a Subtype of Autism Early in Development
3,730 children with a diagnosis of autism or developmental delay had testing for changes in CHD8. Of this group, 15 individuals (children and adults) were found to have changes in CHD8. The majority of these gene changes were not inherited, meaning that neither parent had this genetic change. In addition, the majority of individuals met the diagnostic criteria for autism (13/15), had subtle differences in their facial features, and had a larger-than-average head size. Half or more of the individuals in this group also experienced gastrointestinal (constipation), sleep, and attention issues. Other children had very few health and/or behavior concerns.
McCarthy et al., 2014 - De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism andintellectual disability
In this article, readers will learn that over time, our understanding of the association between a gene and a single illess has changed. Genes that were previously thought to be related to mental illnesses, like schizophrenia, are now thought to have different implications in health and brain function. We now understand that changes in one gene may actually be related to a range of problems related to brain function. This means that one mutatation may cause a mild learning disability in one person, but the same mutation in another person may cause intellectual disability.
This study identified genetic changes (or “mutations”) found in genes that were previously thought to be related to schizophrenia only. As we learn more about genes, we have started to learn that the mutations in the same genes that may be associated with schizophrenia, may also be related to autism or development delay. Therefore, it is believed that CHD8 plays an important role in brain development, and changes in this gene may be related to a range of behavioral and intellectual differences.
O'Roak et al., 2012 (Nature) - Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
In this study, 2,494 samples from the Simon Simplex Collection (SSC) were used to look for 44 genes that have been associated with autism. The SSC study included children with autism and intellectual disability. This study identified 27 de novo (not inherited from either parent) gene changes in 16 genes, including 8 patients with variants in CHD8. Six of those children had larger-than-average head sizes. This physical finding has been seen in other children with different genetic causes of autism (for example, in children with PTEN variants).
O'Roak et al., 2012 (Science) - Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders
Whole exome sequencing was performed for 209 families (677 individuals) who had participated in the Simons Simplex Collection (SSC). The SSC study included children with autism and intellectual disability. This study identified over 100 new candidate genes related to developmental delay, intellectual disability and/or features of autism. Initially, mutations in only two genes – CHD8 and NTNG1 - were found in more than one person. Ffurther analysis of six specific genes (FOXP1, GRIN2B, LAMC3, SCN1A, FOXP2 and GRIN2A) found additional mutations in three of the genes – GRIN2B, LAMC3 and SCN1A - suggesting that there are many various genetic causes of autism and intellectual disability. Several de novo (not inherited from either parent) damaging variants in CHD8 were identified in the SSC samples, while no damaging variants were identified in over 3000 control samples
You can also visit SFARI's website to see information written for researchers about this gene. SFARIgene: CHD8
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