Absent Septum Pellucidum Without Polymicrogyria or Seizures in TCP1-Related Neurodevelopmental Disorder

T-complex protein 1 (TCP1) encodes the TCP1α subunit, one of eight subunits of the chaperonin containing TCP1 ring complex (TRiC). Heterozygous TCP1 variants cause autosomal dominant neurodevelopmental disorder characterized by developmental delay or intellectual disability, seizures, pyramidal or cerebellar signs, and brain malformations, particularly polymicrogyria. However, the reported clinical spectrum remains limited. We report a 4-year-old girl with global developmental delay, speech and motor delay, behavioral dysregulation, microcephaly, hypotonia with core weakness, and a previously unreported heterozygous likely pathogenic TCP1 variant, c.1392delT (p.A465Qfs*3). This frameshift variant is located in exon 11, truncates the final 16.5% of the protein, is predicted to undergo nonsense-mediated decay, and is absent from gnomAD. Biological parental testing was unavailable, precluding determination of variant inheritance. Brain magnetic resonance imaging (MRI) demonstrated an absent septum pellucidum with mild bilateral frontal sulcation/gyration asymmetry without polymicrogyria; the optic nerves and pituitary were normal. No seizures were documented through age 4 years. Additional findings included bicuspid aortic valve with mild aortic insufficiency, asthma, severe eczema/atopy, and multiple food allergies. This case suggests that the molecular and neuroimaging spectrum of TCP1-related neurodevelopmental disorder may be broader than previously recognized; however, a causal association between TCP1 and absent septum pellucidum cannot be established from a single case. The relationship of the cardiac and atopic findings to TCP1 remains uncertain. Additional cases and functional studies are needed to clarify genotype-phenotype relationships.