CHD8 intragenic deletion associated with autism spectrum disorder

Original research article by E.S. Stolerman et al. (2016).

Read the abstract here.

The work presented in this article adds to evidence that changes in the CHD8 gene can play a major role in autism. The researchers describe the clinical features observed in a 9-year-old boy with a de novo (not inherited from either parent) change in the CHD8 gene. The investigators reviewed his medical history, beginning before birth, and generated a time line detailing concerns identified through his childhood.

The child’s early history was typical: he was born at full term, and there were no prenatal complications or major postnatal complications. Typical development behaviors, like making eye contact and otherwise 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 2 years old, it was noted that his speech was not progressing typically and that his social interactions included aggressive behavior, poor eye contact and repetitive behaviors. Common features of the CHD8 change that were observed in this child included gastrointestinal issues, increased head size, and dysmorphic features, while his height, weight, and head circumference were all normal for his age.

The authors provide a comparison of this 9-year-old boy and 18 other children and adults with CHD8 changes. The tables below lists the features seen in each of these 19 people.

Feature Patient
1 2 3 4 5
Sex M M F F M
Age (yrs) 9 8 4 8 12
Mutation Exons 26-28 Deletion Nonsense Deletion truncating Splice site Frameshift indel
Inheritance De novo De novo De novo De novo De novo
Developmental Delay Y Y N/A Y N/A
Intellectual Disability Y Y N Y Y
Verbal IQ N/A 20 90 47 60
Non-Verbal IQ N/A 34 93 41 67
Autism Y Y Y Y Y
Macrocephaly N Y Y Y Y
Gastrointestinal Diarrhea, GERD, Eosinophilic Esophagitis, Duodenitis Constipation, Abdominal pain Constipation N/A Chronic diarrhea


Feature Patient
6 7 8 9 10
Sex M M M M M
Age (yrs) 4 5 13 5 16
Mutation Nonsense Nonsense Deletion (3bp) Frameshift Frameshift
Inheritance De novo N/A De novo N/A N/A
Developmental Delay Y Y Y Y Y
Intellectual Disability N N N Y Y
Verbal IQ 75 79 84 25 6
Non-Verbal IQ 78 92 98 38 19
Autism Y Y Y Y Y
Macrocephaly N Y N Y Y
Gastrointestinal Chronic constipation and loose stool Constipation, Diarrhea None None None


Feature Patient
11 12 13 14 15
Sex M M M M M
Age (yrs) 18 N/A 6 7 17
Mutation Nonsense Missense Nonsense Missense Missense
Inheritance N/A N/A De novo Inherited maternal Inherited paternal
Developmental Delay N N/A Y Y N/A
Intellectual Disability N Y Y N/A N
Verbal IQ N/A N/A 27 N/A 76
Non-Verbal IQ N/A N/A 41 N/A 95
Autism Schizophrenia N/A Y Y Y
Macrocephaly N/A N/A Y N N
Gastrointestinal None N/A Constipation, Dyschezia None Diarrhea, Constipation


Feature Patient
16 17 18 19
Sex F M M F
Age (yrs) 15 13 11 41
Mutation Frameshift Frameshift Deletion single a.a. Frameshift
Inheritance Inherited maternal De novo Unknown De novo
Developmental Delay Y N/A N Y
Intellectual Disability Y Y N Y
Verbal IQ 88 N/A 68 N/A
Non-Verbal IQ 69 N/A 79 N/A
Autism Y Y N N
Macrocephaly Y Y N Y
Gastrointestinal None Constipation Constipation Gastropathy