Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly is a rare, central nervous system malformation syndrome characterized by progressive microcephaly with profound motor delay and intellectual disability, associated with hypertonia, spasticity, clonus, and seizures, with brain imaging revealing severe cerebral and cerebellar atrophy, and poor myelination.

Diencephalic-mesencephalic junction dysplasia syndrome-2 (DMJDS2) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay and hypotonia apparent from infancy. Affected individuals develop severe progressive hyperkinetic movements, including spastic tetraplegia, dystonia, and bulbar dysphagia necessitating tube feeding. Patients are unable to walk and have severely impaired intellectual development with absent speech. Brain imaging shows a unique malformation reflecting abnormal embryonic development of the diencephalic-mesencephalic junction (DMJ), with agenesis of the basal ganglia and olfactory bulb, hypoplasia of the thalamus, and abnormal course of the corticospinal tracts (summary by De Mori et al., 2019). For a discussion of genetic heterogeneity of DMJDS, see DMJDS1 (251280).

Neurodevelopmental disorder with seizures and brain atrophy (NEDSEBA) is an autosomal recessive disorder with highly variable manifestations and severity of these core features. The most severely affected individuals develop symptoms in utero, which may lead to spontaneous abortion or planned termination. Those that survive may present with severe seizures at birth, have poor overall growth with small head circumference, achieve no developmental progress, and show significant brain atrophy and other brain abnormalities. Patients at the mildest end of the phenotypic spectrum have onset of seizures later in childhood and show developmental delay with mildly impaired intellectual development and minimal brain atrophy (summary by Coulter et al., 2020).