45,X/46,XY mosaicism: Clinical manifestations and long term follow-up

Ebba Alkhunaizi^{1

2

3}, Jenna Plamondon Albrecht⁴, Mahmoud Aarabi^{5

6}, Selma F Witchel⁷, Diane Wherrett⁸, Riyana Babul-Hirji^{1

9}, Annie Dupuis¹⁰, Lyne Chiniara¹¹, Eric Chater-Diehl¹², Mary Shago¹², Cheryl Shuman^{1

9}, Aleksandar Rajkovic^{13

14}, Svetlana A Yatsenko^{5

6

15}, David Chitayat^{1

2

9}

Affiliations

¹ Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
² The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
³ Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Cancer Risk and Prevention Clinic, Outpatient Care, Maine Health, Portland, Maine, USA.
⁵ UPMC Medical Genetics & Genomics Laboratories, UPMC Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA.
⁶ Departments of Pathology, and Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁷ Division of Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁸ Division of Endocrinology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Biostatistics, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Pediatrics, Division of Endocrinology, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada.
¹² Department of Pediatric Laboratory Medicine, Cytogenomics Laboratory, Cytogenomics and Genome Resources Facility, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
¹³ Department of Pathology, and Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA.
¹⁴ Institute of Human Genetics, University of California San Francisco, San Francisco, California, USA.
¹⁵ Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA.

PMID: 37882230
DOI: 10.1002/ajmg.a.63451

45,X/46,XY mosaicism: Clinical manifestations and long term follow-up

Ebba Alkhunaizi et al. Am J Med Genet A. 2024 Mar.

. 2024 Mar;194(3):e63451.

doi: 10.1002/ajmg.a.63451. Epub 2023 Oct 26.

Authors

Affiliations

¹ Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
² The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
³ Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁴ Cancer Risk and Prevention Clinic, Outpatient Care, Maine Health, Portland, Maine, USA.
⁵ UPMC Medical Genetics & Genomics Laboratories, UPMC Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA.
⁶ Departments of Pathology, and Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
⁷ Division of Endocrinology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁸ Division of Endocrinology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁹ Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Biostatistics, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Pediatrics, Division of Endocrinology, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada.
¹² Department of Pediatric Laboratory Medicine, Cytogenomics Laboratory, Cytogenomics and Genome Resources Facility, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
¹³ Department of Pathology, and Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, USA.
¹⁴ Institute of Human Genetics, University of California San Francisco, San Francisco, California, USA.
¹⁵ Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA.

PMID: 37882230
DOI: 10.1002/ajmg.a.63451

Abstract

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy.

Keywords: Turner syndrome; abnormal genitalia; gonadal malignancy; growth; infertility; prenatal diagnosis.

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References

REFERENCES

1. Andrade, J. G. R., Guerra-Júnior, G., & Maciel-Guerra, A. T. (2010). 46,XY and 45,X/46,XY testicular dysgenesis: Similar gonadal and genital phenotype, different prognosis. Arquivos Brasileiros de Endocrinologia e Metabologia, 54, 331-334.
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1. Bertelloni, S., Baroncelli, G. I., Massart, F., & Toschi, B. (2015). Growth in boys with 45,X/46,XY mosaicism: Effect of growth hormone treatment on statural growth. Sexual Development, 9, 183-189.
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1. Bondy, C. A. (2007). Care of girls and women with Turner syndrome: A guideline of the Turner syndrome study group. The Journal of Clinical Endocrinology and Metabolism, 92, 10-25.

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45,X/46,XY mosaicism: Clinical manifestations and long term follow-up

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45,X/46,XY mosaicism: Clinical manifestations and long term follow-up

Authors

Affiliations

Abstract

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REFERENCES

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