Tatton-Brown-Rahman Syndrome: Case report and DNMT3A variant not previously reported associated to the syndrome

Abstract

Tatton Brown Rahman Syndrome (TBRS) is a recently described overgrowth syndrome caused by variants in the DNMT3A gene. The description of its phenotype and the differences with its main differential diagnoses are still under development, with very few individuals of Latin American origin described to date. Objective: To describe a Chilean case of TBRS in order to broaden the phenotypic and genotypic spectrum of this new syndrome. Clinical Case: 9-year-old boy diagnosed with TBRS through whole-exome sequencing (WES), which showed a variant in DNMT3A: c.2311C > T, p. (Arg771*) that has not been previously reported in the literature in individuals with the condition. He presented the main characteristics of this syndrome with overgrowth from the neonatal stage, mild intellectual disability associated with autism spectrum disorder, absence of major abnormalities in internal organs, and characteristic dysmorphism with coarse facies, horizontal eyebrows, and prominent upper central incisors. An EEG showed alterations due to frequent interictal epileptiform activity in the left temporal region, with no history of seizures, and normal brain MRI. In addition, he presented advanced bone age, a common finding in other overgrowth syndromes but not frequently reported in TBRS. A sister showed normal genetic study and the segregation study of the variant identified in the parents could not be performed. Conclusions: The report of this case broadens the genotypic spectrum of the syndrome and contributes to the characterization of the phenotypic manifestations including individuals of different ethnicities, emphasizing its most common characteristics and others that hinder its differential diagnosis from other overgrowth syndromes.