Primary microcephaly are genetic conditions that are characterized by small head circumference at birth and always associated with intellectual disability. However, early-onset seizures are prevalent in PNKP-related microcephaly. In this study, we present the clinical and molecular genetics findings of 27 patients carrying biallelic PNKP variants. Our findings showed that hypoplastic frontal lobe when associated with widening of the gyri and cerebellar and brainstem atrophy could point to the diagnosis of PNKP-related microcephaly. Further, the recurrent variants p.Thr424GlyfsTer49, p.Asn461dup and p.Asn461del of PNKP should be screened initially in patients with microcephaly and seizures in our population as a first diagnostic step. This research improves future diagnoses and guide management strategies. (By Professor Ghada M H Abdel-Salam, https://jmg.bmj.com/content/early/2025/12/22/jmg-2025-111040 )