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Ann Pediatr Endocrinol Metab > Volume 28(Suppl 1); 2023 > Article
Kim, Noh, and Cho: A Korean boy with a CHD8 mutation who presented with overgrowth, intellectual disability, and autism


· A CHD8 (chromodomain helicase binding protein 8) mutation was reclassified from Autism, susceptibility to, 18 [MIM 615032] to intellectual developmental disorder with autism and macrocephaly (IDDAM) in May 2022. We present the first IDDAM patient in Korea, a 3-year 10-month-old boy exhibiting overgrowth, intellectual disability, and autism spectrum disorder.
To the editor,
The CHD8 (chromodomain helicase binding protein 8) mutation, initially identified as the cause of autism spectrum disorder (ASD), was previously marked as Autism, susceptibility to, 18 [MIM 615032] on Online Mendelian Inheritance in Man [1]. Due to additional characteristics observed in CHD8 mutation patients, the phenotype was reclassified as intellectual developmental disorder with autism and macrocephaly (IDDAM) in May 2022 [1-3]. In South Korea, only one case with attention deficit hyperactivity disorder and intellectual disability caused by a CHD8 mutation has been reported, but the case did not demonstrate overgrowth features and ASD [4]. We present the first IDDAM patient in South Korea, a 3-year 10-month-old boy exhibiting overgrowth, intellectual disability, and ASD.
The patient visited the division of pediatric endocrinology due to overgrowth. He had been born to nonconsanguineous, healthy South Korean parents at a gestational age of 40+4 weeks without perinatal complications. The birth weight, length, and head circumference were 4,030 g (90.6th percentile), 55 cm (99.7th percentile), and 37.5 cm (99.2th percentile), respectively. At 29 months, he was diagnosed with ASD and developmental delay in cognitive, speech, and motor domains through a neuropsychiatric evaluation by the department of rehabilitation. Brain magnetic resonance imaging showed no specific findings. Chromosomal analysis revealed a normal karyotype (46, XY), and a chromosomal microarray analysis revealed no pathogenic abnormalities.
During the visit, his height, weight, and head circumference were 114 cm (standard deviation scores [SDS], +2.75), 23 kg (SDS, +2.88), and 56 cm (SDS, +3.09), respectively. He had normal body proportions but dysmorphic facial features with frontal bossing, downslanting palpebral fissures, hypertelorism, a high hairline, a long philtrum, and prominent ears. His joints were not hypermobile. Hormonal levels were normal for his age, and bone age was delayed by 10 months. Based on the clinical information and medical history, exome sequencing was performed to screen for genes related to overgrowth, developmental delay, and/or ASD. Targeted exome sequencing identified a heterozygous nonsense mutation c.2854C>T (p.Arg952Ter) in CHD8, and he was diagnosed with IDDAM.
Overgrowth refers to an extreme increase in physical size, including tall stature or abnormal tissue growth in clinical genetics. Genetic overgrowth syndrome refers to nonhormonally-mediated cases, which can accompany varying degrees of intellectual disability, or dysmorphisms [5]. Because the syndromes have overlapping symptoms, genetic testing is useful for accurate diagnosis of overgrowth syndrome [2,3,5]. Our case suggests that CHD8 genetic testing should be included if overgrowth, intellectual disability, and ASD coexist.


Conflicts of interest

No potential conflict of interest relevant to this article was reported.


This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Ethics statement

Written informed consent was obtained from the patient and both parents. This study was approved by the Institutional Review Board of Samsung Medical Center (approval number: 2012-05-080-008).


1. O'Roak BJ, Stessman HA, Boyle EA, Witherspoon KT, Martin B, Lee C, et al. Recurrent de novo mutations implicate novel genes underlying simplex autism risk. Nat Commun 2014;5:5595.
2. Ostrowski PJ, Zachariou A, Loveday C, Beleza-Meireles A, Bertoli M, Dean J, et al. The CHD8 overgrowth syndrome: A detailed evaluation of an emerging overgrowth phenotype in 27 patients. Am J Med Genet C Semin Med Genet 2019;181:557–64.
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3. Tatton-Brown K, Loveday C, Yost S, Clarke M, Ramsay E, Zachariou A, et al. Mutations in epigenetic regulation genes are a major cause of overgrowth with intellectual disability. Am J Hum Genet 2017;100:725–36.
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4. Han JY, Jang JH, Park J, Lee IG. Targeted next-generation sequencing of korean patients with developmental delay and/or intellectual disability. Front Pediatr 2018;6:391.
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5. Ko JM. Genetic syndromes associated with overgrowth in childhood. Ann Pediatr Endocrinol Metab 2013;18:101–5.
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