In 2018, Dobyns et al reported de novo MACF1 variants in eight children with a complex brain malformation: diffuse pachygyria with more severe posterior involvement; flat ventral brainstem with - incosistently - a tiny bump on the ventral surface; pontine clefts, and wiede and flat medulla with visible pyramids on the ventral surface. This pattern appeared likely pathognomonic. Clinical features were severe developmental delay, spasticity, and seizures within the first year.
We found this imaging pattern (>[Fig. 1]) while reviewing unsolved brainstem malformations in an infant presenting in 2006 with infantile spams and microcephaly. On follow-up, this girl had treatment-resistant epilepsy, severe cognitive impairment, no speech, pronounced spastic cerebral palsy resulting in scoliosis, hip dislocation, and multiple contractures, requiring orthopedic interventions. Swallowing was not impaired. Targeted genetic testing confirmed a pathogenic de novo MACF1 variant [c.15682G>T p.(Asp5228Tyr)]. This observation confirms the value of careful pattern recognition and supports the view that this pattern is likely pathognomonic.