Royal College of Surgeons in Ireland
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Five-year assessment of multiple gene variants associated with bone marrow hypocellularity, reduced bone density, and ovarian insufficiency in adolescence

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journal contribution
posted on 2023-02-13, 12:23 authored by E Scott Sills, Conor HarrityConor Harrity, Samuel H. Wood

This study covers the 5-year interval prior to COVID-19 admission for an otherwise healthy 46,XX adolescent expanding the developmental characterization of an unusual convergence of amenorrhea and genetic mutations. The patient experienced rapid collapse of endogenous estradiol output followed by secondary amenorrhea at 13 years of age. Euploid, diffusely hypocellular bone marrow was present on biopsy, although anemia or reduced total immunoglobulin production was not identified. Bone density was 1.5 years below mean; multiple dental anomalies were also documented. While alterations in "master regulator" genes RUNX2, SALL1, and SAMD9 are usually diagnosed in early childhood when missed milestones, dysmorphic features, or chronic infection/immune impairment warrant cross-disciplinary evaluation, this study is the first known report to associate ovarian failure with adolescence with such variants. Immunoglobulin patterns, osseous histomorphology, dentition, hematology/renal screening, pelvic anatomy, ovarian reserve data, and thyroid findings are also correlated. Although severe pathology is typically encountered when any of these genes are disrupted alone, this longitudinal survey reveals that a mild phenotype can prevail if these 3 variants occur simultaneously. Periodic monitoring is planned given the unclassified status of this unique mutation set. 

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The original article is available at https://www.e-jbm.org/

Published Citation

Sills ES, Harrity C, Wood SH. Five-year assessment of multiple gene variants associated with bone marrow hypocellularity, reduced bone density, and ovarian insufficiency in adolescence. J Bone Metab. 2022;29(4):271-277.

Publication Date

30 November 2022

PubMed ID

36529870

Department/Unit

  • Beaumont Hospital
  • Obstetrics and Gynaecology

Publisher

The Korean Society for Bone and Mineral Research

Version

  • Published Version (Version of Record)