A Case Report on Tetrasomy X in a Teenage Girl Presenting with Premature Ovarian Insufficiency

Tetrasomy X (48, XXXX) is an extremely rare sex chromosomal aneuploidy. Very few cases of tetrasomy X with primary ovarian insufficiency have been reported to date, especially from India. The varied heterogeneity of presenting manifestations and also presentation at different ages make diagnosis difficult. Though rare, adolescent case groups make it difficult to accurately diagnose as tetrasomy X. Though rare, cases that presented during adolescence most commonly reported primary or secondary amenorrhea due to primary ovarian insufficiency. Early identification can improve reproductive outcomes as well as the general quality of life through hormone replacement therapy. This current case report describes that of a 16-year-old girl presenting with secondary amenorrhea, poor socio-adaptive functioning, and learning difficulties. Other physical features included ocular hypertelorism, epicanthic folds, a wide nose, and long, slender upper and lower extremities. Secondary sexual characteristics were poorly developed, with absent axillary and pubic hair and infantile external genitalia; however, stage 3 breast development was observed. Imaging studies showed a small uterus and atrophic ovaries. Primary ovarian insufficiency was established by high follicle-stimulating hormone and luteinizing hormone levels. Karyotyping of peripheral lymphocytes by G-banding confirmed tetrasomy X (48, XXXX). Apart from hormone replacement therapy, a multidisciplinary approach for psychosocial rehabilitation was undertaken.

Tetrasomy X, 48 XXXX, primary ovarian insufficiency

1. Huang XY, Tang LF, Zou CC, Zhao ZY. Chromosome analysis in 8158 pediatric patients: an experience of 29 years from Hangzhou, China. Endocrinologist. 2010;20:179-81. [Google Scholar] [Crossref]

2. Queremel Milani DA, Tadi P. Genetics, chromosome abnormalities. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. [Google Scholar] [Crossref]

3. Carr DH, Barr ML, Plunkett ER. An XXXX sex chromosome complex in two mentally defective females. Can Med Assoc J. 1961;84(3):131-7. [Google Scholar] [Crossref]

4. Bilge S, Mert GG, Ozcan N, et al. Tetrasomy X, a rare cause of epilepsy and behavior disorder. Acta Sci Neurol. 2020;3:56-8. [Google Scholar] [Crossref]

5. Rooman RP, Van Driessche K, Du Caju MV. Growth and ovarian function in girls with 48,XXXX karyotype: patient report and review of the literature. J Pediatr Endocrinol Metab. 2002;15:1051-5. [Google Scholar] [Crossref]

6. Kristesashvili J, Asanidze E, Sigua N, Chipashvili M, Kurua E. Premature ovarian insufficiency in an adolescent girl with 48,XXXX karyotype: case presentation and literature review. Gynecol Reprod Endocrinol Metab. 2023;4(1):24-8. [Google Scholar] [Crossref]

7. Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995;96:672-82. [Google Scholar] [Crossref]

8. Unique. Tetrasomy X [Internet]. United Kingdom: Rare Chromosome Disorder Support Group; 2005 [cited 2025 Apr 21]. Available from: https://rarechromo.org/media/information/Chromosome_X/Tetrasomy_X%20FTNW.pdf [Google Scholar] [Crossref]

9. Kara C, Üstyol A, Yılmaz A, Altundağ E, Oğur G. Premature ovarian failure due to tetrasomy X in an adolescent girl. Eur J Pediatr. 2014;173(12):1627-30. [Google Scholar] [Crossref]

10. Wood A, Kleis L, Toriello H, Cemeroglu AP. Mosaic pentasomy X/tetrasomy X syndrome and premature ovarian failure. Indian Pediatr. 2011;48(5):402-4. [Google Scholar] [Crossref]

11. Robinson WP, Binkert F, Schinzel AA, Basaran S, Mikelsaar R. Multiple origins of X chromosome tetrasomy. J Med Genet. 1994;31(5):424-5. [Google Scholar] [Crossref]

12. Shimojima K, Yamamoto S, Imaizumi T, Kumada S, Yamamoto T. Uniparental maternal tetrasomy X co-occurrence with paternal nondisjunction: investigation of the origin of 48,XXXX. Hum Genome Var. 2024;11:31. [Google Scholar] [Crossref]

13. Seo GH, Kang E, Cho JH, Lee BH, Choi JH, Kim GH, et al. Turner syndrome presented with tall stature due to overdosage of the SHOX gene. Ann Pediatr Endocrinol Metab. 2015;20(2):110-3. [Google Scholar] [Crossref]

14. Ottesen AM, Aksglaede L, Garn I, Tartaglia N, Tassone F, Gravholt CH, et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am J Med Genet A. 2010;152A(5):1206-12. [Google Scholar] [Crossref]

15. Jayaraman D, Carvalho KS, Hasbani DM. A case report of hypersomnia in tetrasomy X improved with medical therapy. Clin Case Rep. 2018;6(5):893-5. [Google Scholar] [Crossref]

• Assessment of the Role of Artificial Intelligence in Repositioning TVET for Economic Development in Nigeria
• Teachers’ Use of Assure Model Instructional Design on Learners’ Problem Solving Efficacy in Secondary Schools in Bungoma County, Kenya
• “E-Booksan Ang Kaalaman”: Development, Validation, and Utilization of Electronic Book in Academic Performance of Grade 9 Students in Social Studies
• Analyzing EFL University Students’ Academic Speaking Skills Through Self-Recorded Video Presentation
• Major Findings of The Study on Total Quality Management in Teachers’ Education Institutions (TEIs) In Assam – An Evaluative Study