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Hoyeraal-Hreidarsson syndrome(HHS)

MedGen UID:
337518
•Concept ID:
C1846142
•
Disease or Syndrome
Synonyms: Cerebellar hypoplasia with pancytopenia; Growth retardation prenatal with progressive pancytopenia and cerebellar hypoplasia; HHS
SNOMED CT: Hoyeraal-Hreidarsson syndrome (707276009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
•Concept ID:
C1845977
•
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
See: This record
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
X-linked recessive inheritance (Orphanet)
 
Gene (location): DKC1 (Xq28)
 
Monarch Initiative: MONDO:0018045
OMIM®: 305000
Orphanet: ORPHA3322

Definition

Hoyeraal-Hreidarsson syndrome is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation. [from OMIM]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHoyeraal-Hreidarsson syndrome
Follow this link to review classifications for Hoyeraal-Hreidarsson syndrome in Orphanet.

Professional guidelines

PubMed

The biology and management of dyskeratosis congenita and related disorders of telomeres.
Tummala H, Walne A, Dokal I
Expert Rev Hematol 2022 Aug;15(8):685-696. Epub 2022 Aug 8 doi: 10.1080/17474086.2022.2108784. PMID: 35929966
Treatment of telomeropathies.
Vieri M, Brümmendorf TH, Beier F
Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536
An update on the biology and management of dyskeratosis congenita and related telomere biology disorders.
Niewisch MR, Savage SA
Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. PMID: 31478401Free PMC Article

Recent clinical studies

Etiology

Biallelic TERT variant leads to Hoyeraal-Hreidarsson syndrome with additional dyskeratosis congenita findings.
Çepni E, Satkın NB, Moheb LA, Rocha ME, Kayserili H
Am J Med Genet A 2022 Apr;188(4):1226-1232. Epub 2021 Dec 9 doi: 10.1002/ajmg.a.62602. PMID: 34890115
Treatment of telomeropathies.
Vieri M, Brümmendorf TH, Beier F
Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536
Brain imaging features of children with Hoyeraal-Hreidarsson syndrome.
Zhang MJ, Cao YX, Wu HY, Li HH
Brain Behav 2021 May;11(5):e02079. Epub 2021 Mar 18 doi: 10.1002/brb3.2079. PMID: 33734615Free PMC Article
An update on the biology and management of dyskeratosis congenita and related telomere biology disorders.
Niewisch MR, Savage SA
Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. PMID: 31478401Free PMC Article
Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up.
Burris AM, Ballew BJ, Kentosh JB, Turner CE, Norton SA; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group, Giri N, Alter BP, Nellan A, Gamper C, Hartman KR, Savage SA
Pediatr Neurol 2016 Mar;56:62-68.e1. Epub 2015 Dec 19 doi: 10.1016/j.pediatrneurol.2015.12.005. PMID: 26810774Free PMC Article

Diagnosis

The biology and management of dyskeratosis congenita and related disorders of telomeres.
Tummala H, Walne A, Dokal I
Expert Rev Hematol 2022 Aug;15(8):685-696. Epub 2022 Aug 8 doi: 10.1080/17474086.2022.2108784. PMID: 35929966
Brain imaging features of children with Hoyeraal-Hreidarsson syndrome.
Zhang MJ, Cao YX, Wu HY, Li HH
Brain Behav 2021 May;11(5):e02079. Epub 2021 Mar 18 doi: 10.1002/brb3.2079. PMID: 33734615Free PMC Article
Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up.
Burris AM, Ballew BJ, Kentosh JB, Turner CE, Norton SA; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group, Giri N, Alter BP, Nellan A, Gamper C, Hartman KR, Savage SA
Pediatr Neurol 2016 Mar;56:62-68.e1. Epub 2015 Dec 19 doi: 10.1016/j.pediatrneurol.2015.12.005. PMID: 26810774Free PMC Article
Human telomeres and telomere biology disorders.
Savage SA
Prog Mol Biol Transl Sci 2014;125:41-66. doi: 10.1016/B978-0-12-397898-1.00002-5. PMID: 24993697
Dyskeratosis congenita.
Dokal I
Hematology Am Soc Hematol Educ Program 2011;2011:480-6. doi: 10.1182/asheducation-2011.1.480. PMID: 22160078

Therapy

Complications for a Hoyeraal-Hreidarsson Syndrome Patient with a Germline DKC1 A353V Variant Undergoing Unrelated Peripheral Blood Stem Cell Transplantation.
Chen RL, Lin KK, Chen LY
Int J Mol Sci 2019 Jul 2;20(13) doi: 10.3390/ijms20133261. PMID: 31269755Free PMC Article
Clinical and genetic features of dyskeratosis congenita, cryptic dyskeratosis congenita, and Hoyeraal-Hreidarsson syndrome in Japan.
Yamaguchi H, Sakaguchi H, Yoshida K, Yabe M, Yabe H, Okuno Y, Muramatsu H, Takahashi Y, Yui S, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Inokuchi K, Ito E, Ogawa S, Kojima S
Int J Hematol 2015 Nov;102(5):544-52. Epub 2015 Sep 2 doi: 10.1007/s12185-015-1861-6. PMID: 26329388
Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita.
Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA
Hum Genet 2013 Apr;132(4):473-80. Epub 2013 Jan 18 doi: 10.1007/s00439-013-1265-8. PMID: 23329068Free PMC Article
Dyskeratosis congenita.
Gupta V, Kumar A
Adv Exp Med Biol 2010;685:215-9. doi: 10.1007/978-1-4419-6448-9_20. PMID: 20687509

Prognosis

Phylogenetic analysis of Harmonin homology domains.
Colcombet-Cazenave B, Druart K, Bonnet C, Petit C, Spérandio O, Guglielmini J, Wolff N
BMC Bioinformatics 2021 Apr 14;22(1):190. doi: 10.1186/s12859-021-04116-5. PMID: 33853521Free PMC Article
Gastrointestinal Hemorrhage: A Manifestation of the Telomere Biology Disorders.
Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R, Agarwal S, Jajoo K, Ziegler DS, Kratz CP, Huang J, Lucas TL, Myers KC, Nelson AS, DiNardo CD, Alter BP, Giri N, Khincha PP, McReynolds LJ, Dufour C, Pierri F, Goldman FD, Sherif Y, Savage SA, Miloh T, Bertuch AA
J Pediatr 2021 Mar;230:55-61.e4. Epub 2020 Sep 21 doi: 10.1016/j.jpeds.2020.09.038. PMID: 32971146
Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain.
Jullien L, Kannengiesser C, Kermasson L, Cormier-Daire V, Leblanc T, Soulier J, Londono-Vallejo A, de Villartay JP, Callebaut I, Revy P
Hum Mutat 2016 May;37(5):469-72. Epub 2016 Feb 23 doi: 10.1002/humu.22966. PMID: 26847928
Aplastic anemia and Hoyeraal-Hreidarsson syndrome.
Malbora B, Avci Z, Ozbek N
Skinmed 2014 Mar-Apr;12(2):117-8. PMID: 24933854
Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome.
Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T, Dokal I
Blood 2007 Dec 15;110(13):4198-205. Epub 2007 Sep 4 doi: 10.1182/blood-2006-12-062851. PMID: 17785587Free PMC Article

Clinical prediction guides

Treatment of telomeropathies.
Vieri M, Brümmendorf TH, Beier F
Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536
Phylogenetic analysis of Harmonin homology domains.
Colcombet-Cazenave B, Druart K, Bonnet C, Petit C, Spérandio O, Guglielmini J, Wolff N
BMC Bioinformatics 2021 Apr 14;22(1):190. doi: 10.1186/s12859-021-04116-5. PMID: 33853521Free PMC Article
Brain imaging features of children with Hoyeraal-Hreidarsson syndrome.
Zhang MJ, Cao YX, Wu HY, Li HH
Brain Behav 2021 May;11(5):e02079. Epub 2021 Mar 18 doi: 10.1002/brb3.2079. PMID: 33734615Free PMC Article
Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models.
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
EMBO Mol Med 2019 Jul;11(7):e10201. Epub 2019 Jun 6 doi: 10.15252/emmm.201810201. PMID: 31273937Free PMC Article
Telomere-driven diseases and telomere-targeting therapies.
Martínez P, Blasco MA
J Cell Biol 2017 Apr 3;216(4):875-887. Epub 2017 Mar 2 doi: 10.1083/jcb.201610111. PMID: 28254828Free PMC Article

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