TY - JOUR
T1 - Hoyeraal-Hreidarsson Syndrome due to PARN Mutations
T2 - Fourteen Years of Follow-Up
AU - Burris, Ashley M.
AU - Ballew, Bari J.
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.
N1 - Funding Information:
The authors are grateful to the family for their valuable contributions to our understanding of Hoyeraal-Hreidarsson syndrome. Lisa Cartwright, MD, Pediatric Urology, Walter Reed National Military Medical Center (WRNNMC) is acknowledged for recognizing the atypical features of this patient and placing the initial referral to dermatology in 2006. Daniel Cordaro, MD, Hematopathology, WRNNMC, is acknowledged for evaluation of bone marrow biopsies. Outstanding study support was provided by Lisa Leathwood, RN; Maureen Risch, RN; and Ann Carr, CGC, MS, Westat, Inc. The Bone Marrow Transplant Program at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Hospital, is acknowledged for their participation in the care of this patient.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - CNS calcification
KW - Hoyeraal-Hreidarsson syndrome
KW - PARN
KW - dyskeratosis congenita
KW - microcephaly
KW - telomere
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UR - http://www.scopus.com/inward/citedby.url?scp=84955308120&partnerID=8YFLogxK
U2 - 10.1016/j.pediatrneurol.2015.12.005
DO - 10.1016/j.pediatrneurol.2015.12.005
M3 - Article
C2 - 26810774
AN - SCOPUS:84955308120
SN - 0887-8994
VL - 56
SP - 62-68.e1
JO - Pediatric Neurology
JF - Pediatric Neurology
ER -