TYMS-ENOSF1 Dyskeratosis Congenita in a Patient With Ring Chromosome 18: A Case Report.

Dyskeratosis Congenita (DC) is a rare genetic syndrome due to variants in genes involved in telomeric regulation and maintenance, impacting multiple organ systems. We report a case of DC secondary to TYMS gene deletion in a patient with ring chromosome 18 and related partial monosomy 18p and 18q. TYMS encodes thymidylate synthase, and compound heterozygosity for loss of function variants in TYMS and a specific haplotype of its antisense regulator ENOSFI (enolase super family 1) causes digenic DC. The patient had physical and developmental features of 18p monosomy, including poor growth, feeding issues, distinctive facial features, and strabismus. In early infancy, he developed diffuse hyperpigmentation as well as numerous punctate hypopigmented macules, sparse hair, and nail dystrophy, and diagnosis of DC was confirmed with a telomere length assay. Our case highlights that individuals with deletions at 18p encompassing TYMS should be evaluated for features of digenic dyskeratosis congenita.