2.1 | Patients
We recruited pediatric patients with microcephaly, applying a definition of microcephaly of OFC >2 standard deviations below the mean for same sex, age-matched Korean references, between January 2014 and December 2018 at Samsung Medical Center in Seoul, Korea. All affected individuals were evaluated for clinical features and diagnosed with microcephaly by two pediatric neurologists. We excluded patients with microcephaly that resulted from cerebral insults related to defined perinatal problems such as congenital infection, teratogens, physical environment, or maternal medical condition through laboratory tests, brain imaging, and detailed history taking. We performed WES for all patients and CMA or low-depth whole genome sequencing (LD-WGS) to analyze copy number variation (CNV). We measured weights, heights, and HCs in the same examination and evaluated concordance between the body gauges. Clinical phenotypes included the followings; infantile hypotonia, facial dysmorphism, skeletal and organ anomalies, hearing loss, developmental delay/cognitive impairment, seizure, and affected epilepsy syndrome. Development and cognitive function was assessed using Bayley Scales of Infant Development (BSID-III) or Wechsler Scale of Intelligence for children (WISC-V), depending on the age of the patients. If these scales were not available, we estimated developmental stage or cognitive function based on the clinical status assessed by two pediatric neurologists using the same standards.