Fatal hyperkeratosis syndrome in four siblings due to dolichol kinase deficiency

摘要

A diagnostic journey began in 1966 when a male was born with a lethal hyperkeratosis of undetermined etiology, only to be followed by three additional siblings with the same unknown disorder. All four siblings had unique circumferential skin constrictions on all of their digits. They died within 5 days after birth with no diagnosis or etiology established. The first author (BDH) maintained notes, partial medical records, photographs, and comments about one autopsy report. This information was regularly revisited in the hope of finding a literature match, but no etiological diagnosis was forthcoming. However, in 2017, Rush et al. reported two siblings with similar phenotype in whom they found dolichol kinase deficiency (DOLK). Ultimately, our family was relocated and DNA isolated from the pathology slides of the third affected infant showed compound heterozygous pathogenic variants in the DOLK gene. The variants were in trans, with different missense variants from the mother and father. This 52-year diagnostic pursuit, culminated in an answer that gave the family an explanation for their losses.