Brain imaging features of children with Hoyeraal-Hreidarsson syndrome

Brain Behav. 2021 May;11(5):e02079. doi: 10.1002/brb3.2079. Epub 2021 Mar 18.

Abstract

Objective: This study aimed to summarize the magnetic resonance imaging (MRI) and computed tomography (CT) features of the central nervous system (CNS) in children with Hoyeraal-Hreidarsson syndrome.

Methods: The imaging and clinical data of four children diagnosed with Hoyeraal-Hreidarsson syndrome by clinical and laboratory tests in the Guangzhou Women and Children's Medical Center were gathered and analyzed retrospectively. The clinical manifestations and CNS imaging features of Hoyeraal-Hreidarsson syndrome were summarized based on our results and a literature review.

Results: Our results showed that delayed development, skin pigmentation, nail/toenail dystrophy, thrombocytopenia, and anemia are the most observed clinical presentations of Hoyeraal-Hreidarsson syndrome. Important findings on CNS imaging showed that all patients had cerebellar hypoplasia, delayed myelination, hydrocephalus, brain atrophy, and calcification. The gene mutations in all cases were consistent with those of dyskeratosis congenita, including TINF2 mutations in three cases and DKC1 mutations in one case.

Conclusion: Hoyeraal-Hreidarsson syndrome is a severe variant of dyskeratosis congenita. Both DKC1 and TINF2 mutations can lead to the phenotypes of Hoyeraal-Hreidarsson syndrome. In our study, CNS imaging revealed that cerebellar hypoplasia has an important diagnostic value for Hoyeraal-Hreidarsson syndrome while delayed myelination, calcification of the parenchyma, brain atrophy, and hydrocephalus are also important findings on CNS imaging. Combining imaging features with clinical and laboratory indicators can assist the diagnosis of Hoyeraal-Hreidarsson syndrome.

Keywords: DKC1; Hoyeraal-Hreidarsson syndrome; TINF2; cerebellar hypoplasia; dyskeratosis congenita.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Cell Cycle Proteins / genetics
  • Child
  • Dyskeratosis Congenita*
  • Female
  • Fetal Growth Retardation
  • Humans
  • Intellectual Disability
  • Microcephaly
  • Mutation
  • Neuroimaging
  • Nuclear Proteins / genetics
  • Retrospective Studies

Substances

  • Cell Cycle Proteins
  • DKC1 protein, human
  • Nuclear Proteins

Supplementary concepts

  • Hoyeraal Hreidarsson syndrome