Hoyeraal-Hreidarsson syndrome

Hoyeraal-Hreidarsson syndrome
This condition is inherited in an X-linked recessive manner
Specialty Medical genetics Edit this on Wikidata

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 retardation.[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]


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.[2]

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.[1]

Diagnosis

  • Neuroimaging - Cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications.
  • Molecular genetic testing - for confirmation.

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.

See also

References

  1. 1 2 3 Glousker G, Touzot F, Revy P, Tzfati Y, Savage SA (2015). "Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder". Br. J. Haematol. 170: 457–71. doi:10.1111/bjh.13442. PMC 4526362. PMID 25940403.
  2. 1 2 Knight SW, Heiss NS, Vulliamy TJ, Aalfs CM, McMahon C, Richmond P, Jones A, Hennekam RC, Poustka A, Mason PJ, Dokal I (1999). "Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1". Br. J. Haematol. 107 (2): 335–9. doi:10.1046/j.1365-2141.1999.01690.x. PMID 10583221.
  3. ↑ Deng Z, Glousker G, Molczan A, Fox AJ, Lamm N, Dheekollu J, Weizman OE, Schertzer M, Wang Z, Vladimirova O, Schug J, Aker M, Londoño-Vallejo A, Kaestner KH, Lieberman PM, Tzfati Y (2013). "Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome". Proc. Natl. Acad. Sci. U.S.A. 110 (36): E3408–16. doi:10.1073/pnas.1300600110. PMC 3767560. PMID 23959892.
  4. ↑ Le Guen T, Jullien L, Touzot F, Schertzer M, Gaillard L, Perderiset M, Carpentier W, Nitschke P, Picard C, Couillault G, Soulier J, Fischer A, Callebaut I, Jabado N, Londono-Vallejo A, de Villartay JP, Revy P (2013). "Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability". Hum Mol Genet. 22 (16): 3239–49. doi:10.1093/hmg/ddt178. PMID 23591994.
  5. ↑ 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.
Classification


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