Abstract

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.

Characteristics

The currently recognized features of HHS are cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth retardation. HHS patients also commonly exhibit symptoms such as microcephaly, aplastic anemia, and mental retardation.

Characteristics | Overlap with dyskeratosis congenita

In addition to HHS-specific sequelae, HHS patients frequently present with the mucocutaneous triad of nail dysplasia, lacy skin pigmentation, and oral leukoplakia

Pathogenesis

Although the pathogenesis of HHS remains unknown, it is strongly suspected that the clinical sequelae of HHS arise from the accelerated telomere shortening present in HHS patients.

Treatment

Treatment is supportive.

- The aplastic anemia and immunodeficiency can be treated by bone marrow transplantation.

- Supportive treatment for gastrointestinal complications and infections.

- Genetic counselling.