CHD8 haploinsufficiency causes a distinct neurodevelopmental syndrome

Heba Yasin, William T Gibson, Sylvie Langlois, Robert M Stowe, Erica S Tsang, Leora Lee, Jenny Poon, Grant Tran, Christine Tyson, Chi Kin Wong, Marco A Marra, Jan M Friedman, Farah R Zahir


In 2007 we first reported that loss of genetic material that included a gene called CHD8 may cause a new syndrome that doctors can recognize. Now, a dozen years later we are happy to know our finding is confirmed and indeed there is a syndrome caused when this gene is mutated. The syndrome has Autism, and Intellectual Disability and several other features. We are now focussing on finding a cure and better treatment for the disorder. Finding the best treatments and preventative strategies and cures, requires first that we are sure about the disease we are studying. This paper confirms that this is a new disease and explains it in detail.


After 12 years upon suggesting the new syndrome. We have now collated information on over 50 reported patients internationally. We have also comprehensively reviewed their clinical presentation to present the most up-to-date complete overview of the disorder. This will be very useful to the clinical community and already we are seeing real-world impact.

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Dr. Farah Zahir, PhD
Dr. Farah Zahir, PhD
University of British Columbia
Personally, this paper was the culmination of 12 years of tracking the syndrome I first suggested existed, when I published as a Masters student in 2007, the first report of CHD8 haploinsufficiency. I have had several doctors contact me after we published this paper and that is what makes all the long effort worth it - knowing our findings are helping clinicians and patients all over the world. Dr. Farah Zahir, PhD

A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8.

J Hum Genet 2019 Apr 22;64(4):271-280. Epub 2019 Jan 22.

College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar.

A decade ago, we described novel de novo submicroscopic deletions of chromosome 14q11.2 in three children with developmental delay, cognitive impairment, and similar dysmorphic features, including widely-spaced eyes, short nose with flat nasal bridge, long philtrum, prominent Cupid's bow of the upper lip, full lower lip, and auricular anomalies. We suggested that this constituted a new multiple congenital anomaly-intellectual disability syndrome due to defects in CHD8 and/or SUPT16H. The three patients in our original cohort were between 2 years and 3 years of age at the time. Here we present a fourth patient and clinical updates on our previous patients. To document the longitudinal course more fully, we integrate published reports of other patients and describe genotype-phenotype correlations among them. Children with the disorder present with developmental delay, intellectual disability, and/or autism spectrum disorder in addition to characteristic facies. Gastrointestinal and sleep problems are notable. The identification of multiple patients with the same genetic defect and characteristic clinical phenotype, confirms our suggestion that this is a syndromic disorder caused by haploinsufficiency or heterozygous loss of function of CHD8.

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April 2019
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