Hoyeraal-Hreidarsson syndrome
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.[1][2] 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 restriction.[1] The primary cause of death in HHS is bone marrow failure, but mortality from cancer and pulmonary fibrosis is also significant.[3][4][5]
Presentation[edit | edit source]
The currently recognized features of HHS are cerebellar hypoplasia, immunodeficiency, progressive bone marrow failure, and intrauterine growth restriction. HHS patients also commonly exhibit symptoms such as microcephaly, aplastic anemia, and intellectual disability.[2]
Overlap with dyskeratosis congenita[edit | edit source]
In addition to HHS-specific sequelae, HHS patients frequently present with the mucocutaneous triad of nail dysplasia, lacy skin pigmentation, and oral leukoplakia
Pathogenesis[edit | edit source]
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.[1]
It has been associated with mutations in the poly(A)-specific ribonuclease PARN gene.[6]
Diagnosis[edit | edit source]
- Neuroimaging - Cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications.
- Molecular genetic testing - for confirmation.
Treatment[edit | edit source]
Current treatment is supportive.[citation needed]
- The aplastic anemia and immunodeficiency can be treated by bone marrow transplantation.
- Supportive treatment for gastrointestinal complications and infections.
- Genetic counselling.
TeloCure Ltd. TeloCure Ltd. is developing gene therapy solutions for HHS. The company is funded by the foundation for Noga Baumatz and other HHS patients which was founded by the family of a deceased HHS patient.
See also[edit | edit source]
References[edit | edit source]
- ↑ 1.0 1.1 1.2
- ↑ 2.0 2.1
- ↑
- ↑
- ↑ Jullien L, Kannengiesser C, Kermasson L, Cormier-Daire V, Leblanc T, Soulier J, Londono-Vallejo A, de Villartay JP, Callebaut I, Revy P, Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain, Hum Mutat. 2016 May;37(5):469-72.doi: 10.1002/humu.22966.
- ↑ Benyelles M, Episkopou H, O'Donohue MF, Kermasson L, Frange P, Poulain F, Burcu Belen F, Polat M, Bole-Feysot C, Langa-Vives F, Gleizes PE, de Villartay JP, Callebaut I, Decottignies A, Revy P (2019) Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models. EMBO Mol Med 11(7):e10201
External links[edit | edit source]
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Contributors: Prab R. Tumpati, MD
