Hoyeraal-Hreidarsson syndrome (HHS) is a very rare multisystem X-linked recessive disorder characterized by excessively short telomeres and is considered a severe form of dyskeratosis congenita. Being an X-linked disorder, HHS primarily affects males. Patients with HHS typically present in early childhood with cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth retardation. The primary cause of death in HHS is bone marrow failure, but mortality from cancer and pulmonary fibrosis is also significant.
he disease generally affects primarily males and presents in early childhood. Growth retardation is usually of prenatal onset.
Other clinical manifestations include:
- Intellectual disability
- Mucocutaneous lesions (hyperpigmentation, nail dystrophy, premalignant leukoplakia affecting oral and gastrointestinal mucosa)
- Immunodeficiency and pancytopenia.
- Early onset bone marrow failure
Cancer predisposition is also reported.
HSS is caused by mutations in the DCK1 gene (Xq28), encoding the nucleolar protein dyskerin which interacts with the human telomerase RNA complex. Mutations in other genes involved in telomere maintenance may be associated with this disorder (TERT, RTEL1 or TINF2).
The prognosis is poor as the disease follows a very severe course and premature death in childhood can occur due to bone marrow failure.