Biallelic TERT variant leads to Hoyeraal-Hreidarsson syndrome with additional dyskeratosis congenita findings

Am J Med Genet A. 2022 Apr;188(4):1226-1232. doi: 10.1002/ajmg.a.62602. Epub 2021 Dec 9.


Short telomere syndromes constitute a heterogeneous group of clinical conditions characterized by short telomeres and impaired telomerase activity due to pathogenic variants in the essential telomerase components. Dyskeratosis congenita (DC) is a rare, multisystemic telomere biology disorder characterized by abnormal skin pigmentation, oral leukoplakia and nail dysplasia along with various somatic findings. Hoyeraal-Hreidarsson syndrome (HHS) is generally an autosomal recessively inherited subgroup showing growth retardation, microcephaly, cerebellar hypoplasia and severe immunodeficiency. We here report on a consanguineous family from Turkey, in which a missense variant in the reverse transcriptase domain of the TERT gene segregated with short telomere lengths and was associated with full-blown short telomere syndrome phenotype in the index; and heterogeneous adult-onset manifestations in heterozygous individuals.

Keywords: Hoyeraal-Hreidarsson syndrome; TERT; dyskeratosis congenita; telomerase; telomere biology disorders.

Publication types

  • Case Reports

MeSH terms

  • Dyskeratosis Congenita* / diagnosis
  • Dyskeratosis Congenita* / genetics
  • Dyskeratosis Congenita* / pathology
  • Fetal Growth Retardation
  • Humans
  • Intellectual Disability* / genetics
  • Microcephaly* / diagnosis
  • Microcephaly* / genetics
  • Microcephaly* / pathology
  • Mutation
  • Telomerase* / genetics
  • Telomerase* / metabolism
  • Telomere / genetics


  • TERT protein, human
  • Telomerase

Supplementary concepts

  • Hoyeraal Hreidarsson syndrome