A Korean boy with a CHD8 mutation who presented with overgrowth, intellectual disability, and autism

Kim, Chiwoo; Kim, Min-Sun; Noh, Eu-seon; Bae, Ga young; Jang, Ja-Hyun; Lee, Sae-Mi; Cho, Sung Yoon; Lee, Jeehun; Jin, Dong-Kyu

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Ann Pediatr Endocrinol Metab > Accepted Articles

Case report

DOI: https://doi.org/10.6065/apem.2244130.065 [Accepted] Published online February 1, 2023.

A Korean boy with a CHD8 mutation who presented with overgrowth, intellectual disability, and autism

Chiwoo Kim¹, Min-Sun Kim², Eu-seon Noh², Ga young Bae², Ja-Hyun Jang³, Sae-Mi Lee^4,5, Sung Yoon Cho²

, Jeehun Lee², Dong-Kyu Jin²

¹Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
²Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
³Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
⁴GC Genome, Yongin, South Korea
⁵Department of Laboratory Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea

Address for correspondence: Sung Yoon Cho
Email: nadri1217@naver.com

Received: May 26, 2022 Revised: June 28, 2022 Accepted: August 9, 2022

Abstract

The CHD8 mutation was initially identified as the cause of autism spectrum disorder (ASD) and was previously marked as Autism, susceptibility to, 18 [MIM 615032] on Online Mendelian Inheritance in Man (OMIM). As many patients with CHD8 mutation showed other characteristics along with autism, the phenotype was relabeled as intellectual developmental disorder with autism and macrocephaly (IDDAM) in May 2022. We report a 3-year 10-month-old boy who presented with overgrowth, intellectual disability, dysmorphic facial features, and ASD. Targeted exome sequencing identified a heterozygous nonsense mutation c.2854C>T (p.Arg952Ter) in CHD8, and he was diagnosed with IDDAM. Overgrowth patients with dysmorphic face and/or developmental delay should be investigated for genetic causes. Such causes have been reported in about 50% of patients diagnosed with overgrowth with intellectual disability. Our case suggests that CHD8 genetic testing should be included if overgrowth, intellectual disability, and ASD coexist.

Keywords: CHD8, overgrowth, intellectual disability, autism spectrum disorder, intellectual developmental disorder with autism and macrocephaly