Expansion of the Phenotype of You-Hoover-Fong Syndrome and Possible Increased Risk of Cancer.

Abstract

You-Hoover-Fong syndrome (YHFS) is a rare autosomal recessive disorder characterized by global developmental delay, microcephaly, dysmorphic facial features, and a spectrum of neurodevelopmental abnormalities. YHFS is caused by pathogenic variants in TELO2, a gene involved in regulation of the cell cycle. To date, 29 individuals with YHFS have been reported and none of them has been reported to develop tumors. We describe two siblings with YHFS both presenting with bilateral acoustic nerve agenesis, microcephaly, and dysmorphic features. Notably, one sibling developed hepatoblastoma at the age of 7.5 years. Clinical exome sequencing revealed in both siblings compound heterozygous variants in the TELO2 gene. Although the development of hepatoblastoma might be coincidental, given the role of TELO2 in cell cycle, we suspect YHFS might be associated with an increased cancer susceptibility. Further cases are needed to confirm whether YHFS is associated with an increased risk of cancer.