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.