3.1 | Clinical phenotypes
Among 40 patients (female:male = 22:18) with microcephaly, 34 patients
presented at birth with primary microcephaly and the remaining six were
identified as cases of secondary microcephaly based on the gradual
development of a small HC after birth (Table 1). With proportionate
microcephaly, identified in 15 patients (37.5%), all body gauges were
below the sex and age-matched 3rd centile value. The
other 25 patients (62.5%) showed disproportionate microcephaly, with
height and/or weight in the normal range for sex and age. All patients
with short stature (n = 26) displayed type 3 failure to thrive
during their infancy. Common features observed in all patients were
infantile hypotonia and developmental delay. The average age at the time
of participation in this study was 5.28 ± 4.60 years old. Thirty-two
patients showed noticeable developmental delay or intellectual
disability. Of the remaining patients, one showed mild intellectual
disabilities and seven displayed a delay (5 months below age) in
reaching developmental milestones. Preschool-aged patients (n =
25) also lagged in achieving developmental milestones, and eight
school-aged patients received special education. Four patients were
treated for autistic spectrum disorder (n = 3) or behavioral
disorder (n = 1) in a neuropsychiatric clinic. Seven patients
showed frequent dystonia or other involuntary movements like chorea,
athetoid movements, or tremor.
Seventeen patients (42.5%) showed various accompanying anomalies,
including congenital heart anomaly (n = 8), skeletal anomaly
(n = 4), and cleft lip and/or palate (n = 5) (Table 1).
Three patients developed sensorineural hearing loss without a
discernible etiology. Dysmorphic features were evident in more than half
of patients (n = 28, 70%), these features were clear in 17
patients (42.5%) and notably vague in 11 patients (27.5%).
Twenty-seven patients (67.5%) had seizures. One of these patients had
only one seizure episode provoked by febrile illness. Among the 26
patients with epilepsy, 11 showed intractable epilepsy, with having
frequent seizures despite multiple antiepileptic medications. There were
eight patients diagnosed with epileptic encephalopathy, including six
patients with Lennox-Gastaut syndrome (LGS). Half of patients with LGS
showed infantile spasms, and one patient had a neonatal seizure.
Brain MRIs were performed in all patients, and abnormal structural
lesions were found in six patients. Three patients had agenesis or
hypoplasia of the corpus callosum with microcephaly. In another three
patients, holoprosencephaly, subependymal heterotopia, and hypoplasia of
the pons and cerebellum were found, respectively. Thirty-four patients
showed normal brain structure by MRI.