Diagnosis and clinical presentation of two individuals with a rare TCF20 pathogenic variant

Abstract

TCF20-associated neurodevelopmental disorder (TAND) is a rare and phenotypically variable genetic condition. Common features include intellectual disability, neurobehavioural concerns, postnatal tall stature and hypotonia.Two unrelated early adolescent males were referred to genetics for assessment of developmental delay. The first male of Caucasian descent had a history of autism spectrum disorder (ASD), mitral valve prolapse and subtle craniofacial dysmorphisms. The second male of Somali descent had a history of intellectual disability, thick corpus callosum and ASD. Whole-exome sequencing revealed a pathogenic variant in TCF20 in both individuals. Further testing revealed that the former individual's mother was mosaic for the TCF20 pathogenic variant.We report two individuals with TCF20 pathogenic variants presenting with unique findings, including thick corpus callosum, family history of mosaicism and cardiac anomalies. These examples expand the TAND phenotype, describe associated dysmorphism in a minority group and highlight the importance of rare disease research.

Keywords: Developmental paediatrocs; Genetic screening / counselling; Medical education; Paediatrics.

Figure 1

Pedigree. Pedigree of patient A, including ages and relevant comorbidities of family members. ASD, autism spectrum disorder.

Figure 2

Neuroimaging findings. Brain MRI of patient B, at 11 years of age, showing abnormally appearing corpus callosum with overall thickening and slightly lobulated contour (arrows) on MP-RAGE T1-weighted sagittal plane.

Figure 3

TCF20 genetic testing findings. (A) In patient A, a missense variant (c558G>A, p.W1861X) in the TCF20 gene was detected in the proband (upper panel) as well as in mosaic form in the proband’s mother. Read alignments are sorted by change in base first. Figure supplied by GeneDx Laboratory. (B) In patient B, a missense variant (NM-005650.3:c.1261A>T, pThr421Ser) in the TCF20 gene was detected in the proband (upper panel) and absent in either parent (middle and lower panel) in a trio whole-exome sequencing, consistent with de novo occurrence. Figure and legend supplied by Fulgent laboratory (B).