Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up

Ashley M. Burris, Bari J. Ballew, Joshua B. Kentosh, Clesson E. Turner, Scott A. Norton, Neelam Giri, Blanche P. Alter, Anandani Nellan, Christopher Gamper, Kip R. Hartman, Sharon A. Savage

Research output: Contribution to journalArticle

Abstract

Background Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita-related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. Patient Description We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. Conclusions This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.

Original languageEnglish (US)
Pages (from-to)62-68
Number of pages7
JournalPediatric Neurology
Volume56
DOIs
StatePublished - Mar 1 2016

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Mutation
Fetal Growth Retardation
Oral Leukoplakia
Skin Pigmentation
Urethral Stricture
Esophageal Stenosis
Nails
Central Nervous System
Dyskeratosis Congenita
Bone Marrow
Exome
Microcephaly
Osteonecrosis
Germ-Line Mutation
Myelodysplastic Syndromes
Cell Transplantation
Telomere
Genetic Counseling
Hoyeraal Hreidarsson syndrome
Hip

Keywords

  • CNS calcification
  • dyskeratosis congenita
  • Hoyeraal-Hreidarsson syndrome
  • microcephaly
  • PARN
  • telomere

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Burris, A. M., Ballew, B. J., Kentosh, J. B., Turner, C. E., Norton, S. A., Giri, N., ... Savage, S. A. (2016). Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up. Pediatric Neurology, 56, 62-68. https://doi.org/10.1016/j.pediatrneurol.2015.12.005

Hoyeraal-Hreidarsson Syndrome due to PARN Mutations : Fourteen Years of Follow-Up. / Burris, Ashley M.; Ballew, Bari J.; Kentosh, Joshua B.; Turner, Clesson E.; Norton, Scott A.; Giri, Neelam; Alter, Blanche P.; Nellan, Anandani; Gamper, Christopher; Hartman, Kip R.; Savage, Sharon A.

In: Pediatric Neurology, Vol. 56, 01.03.2016, p. 62-68.

Research output: Contribution to journalArticle

Burris, AM, Ballew, BJ, Kentosh, JB, Turner, CE, Norton, SA, Giri, N, Alter, BP, Nellan, A, Gamper, C, Hartman, KR & Savage, SA 2016, 'Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up', Pediatric Neurology, vol. 56, pp. 62-68. https://doi.org/10.1016/j.pediatrneurol.2015.12.005
Burris, Ashley M. ; Ballew, Bari J. ; Kentosh, Joshua B. ; Turner, Clesson E. ; Norton, Scott A. ; Giri, Neelam ; Alter, Blanche P. ; Nellan, Anandani ; Gamper, Christopher ; Hartman, Kip R. ; Savage, Sharon A. / Hoyeraal-Hreidarsson Syndrome due to PARN Mutations : Fourteen Years of Follow-Up. In: Pediatric Neurology. 2016 ; Vol. 56. pp. 62-68.
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abstract = "Background Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita-related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60{\%} of individuals with Hoyeraal-Hreidarsson syndrome. Patient Description We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN. Conclusions This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.",
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AU - Kentosh, Joshua B.

AU - Turner, Clesson E.

AU - Norton, Scott A.

AU - Giri, Neelam

AU - Alter, Blanche P.

AU - Nellan, Anandani

AU - Gamper, Christopher

AU - Hartman, Kip R.

AU - Savage, Sharon A.

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