Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature

Abstract

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information.

Results: The cohort of 27 patients all had novel variants, and ranged in age from 2 to 68 years. All had developmental delay/intellectual disability. Autism spectrum disorders/autistic features were reported in 69%, attention disorders or hyperactivity in 67%, craniofacial features (no recognizable facial gestalt) in 67%, structural brain anomalies in 24%, and seizures in 12%. Additional features affecting various organ systems were described in 93%. In a majority of patients, we did not observe previously reported findings of postnatal overgrowth or craniosynostosis, in comparison with earlier reports.

Conclusion: We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20.

Keywords: TCF20; autism; developmental delay; exome; intellectual disability.

Figure 1:. TCF20 variants.

Upper panel: Genomic structure of the TCF20 gene. Exons are shown to scale with the coding sequence in color and untranslated regions in black. The position of the first coding nucleotide is shown in exon 2, and numbers in other black boxes indicate cDNA numbering of the last nucleotides of exon boundaries or last nucleotide of stop codons. Introns are depicted by black horizontal dashed line and sizes are not indicated. Novel variants are represented in black stars, and previously reported variants are represented in red circles, blue squares, green triangles, and purple pentagons. De novo novel variants are italicized. Lower panel: Diagram representing the TCF20 protein with previously annotated domains. TAD, trans activation domain. Q1/Q2, glutamine-rich stretches. P1-P3, PEST domains. N1-N3, nuclear localisation signals. MD, minimal DNA binding domain. ZNF, zinc finger domain. ePHD/ADD, extended plant homeodomain/ATRX-DNMT3-DNMT3L.

Figure 2:. Facial appearance of individuals with variants in TCF20.

While minor craniofacial anomalies are noted in the majority of patients, a specific gestalt has not emerged. A, Patient 2. B, Patient 11. C, Patient 21. D, Patients 17a-c.