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.