Supplementary Material for: Prenatal Diagnosis of Tubulinopathy: Case Report of Neurosonographic Features and a Novel TUBA1A Variant

Introduction: Tubulinopathies are a heterogeneous group of rare disorders which are primarily characterized by brain malformations caused by pathogenic variants in the genes that encode tubulin. Although scarce, prenatal diagnosis has been recently reported through expert neurosonography and magnetic resonance imaging (MRI), most commonly at 28-34 weeks’ gestation, followed by identification of pathogenic variant in TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, or TUBG1 using gene sequencing.
Case Presentation: We present detailed ultrasound findings of 21-week fetus with brain abnormalities including low normal head circumference (HC), cerebellar hypoplasia, dysmorphic cavum vellum pellucidum (CSP), partial agenesis and dysgenesis of the corpus callosum, distortion with interdigitation of the interhemispheric fissure, ventricular asymmetry with dysmorphic and/or dilated frontal horns, as well as asymmetry in the basal ganglia.
Amniocentesis with trio genome sequencing (GS) detected a novel, de novo heterozygous c.799T>C variant in TUBA1A that has not been previously reported.
Conclusions: This case offers a detailed characterization of the subtle neurosonographic phenotype in this fetus with early manifestation of malformations of cortical development
(MCD) related to tubulinopathy and provides information regarding the novel variant in the TUBA1A gene. It further underscores the importance of neurosonography and genetic analysis in identifying tubulinopathies and informing clinical decision-making during pregnancy.