Hoyeraal-Hreidarsson syndrome

Hoyeraal-Hreidarsson syndrome
Classification and external resources
Specialty medical genetics
ICD-10 Q82.8
ICD-9-CM 757.39
OMIM 305000
DiseasesDB 32955
MeSH C536068

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]

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]

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. 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 3767560Freely accessible. 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.



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