This article has Open Peer Review reports available.
Clinical correlation between premature ovarian failure and a chromosomal anomaly in a 22-year-old Caucasian woman: a case report
© Dell'Edera et al.; licensee BioMed Central Ltd. 2012
Received: 5 June 2012
Accepted: 20 September 2012
Published: 29 October 2012
Premature ovarian failure is defined as the cessation of ovarian activity before the age of 40 years. It is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone and follicle-stimulating hormone).
Our patient, a 22-year-old Caucasian woman under evaluation for infertility, had experienced secondary amenorrhea from the age of 18. No positive family history was noted regarding premature menopause. An examination of our patient’s karyotype showed the presence of a reciprocal translocation, apparently balanced, which had the X chromosome long arm (q13) and the 14 chromosome short arm (p12) with consequent karyotype: 46, X, t(X; 14)(q13;p12).
Our study has underlined that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It highlighted a genetic etiology, in the form of a chromosomal abnormality, as the causal factor in amenorrhea.
Premature ovarian failure (POF) is defined by the cessation of ovarian activity before the age of 40 years. This condition is biochemically characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)).
POF is considered idiopathic in two thirds of cases, with the patient having a normal karyotype; in the remaining third of cases, it is secondary to genetic anomalies, autoimmune pathologies, pharmacological therapies, radiotherapy, or surgical oophorectomy.
In the absence of surgical oophorectomy, chemotherapy or pelvic radiation, POF encompasses a heterogeneous spectrum of conditions through two major mechanisms, follicle dysfunction and follicle depletion. Although there are many other reasons for ovarian failure, genetic or chromosomal causes are the most important as their presence affects subsequent management.
Our study emphasizes that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It highlights a genetic etiology, in the form of a chromosomal abnormality, as the causal factor in amenorrhea.
Our patient, a 22-year-old Caucasian woman under evaluation for infertility, had experienced secondary amenorrhea from the age of 18 years. She had received hormonal replacement for the past two years, which resulted in cyclical bleeding, but she remained anovulatory. No positive family history was noted regarding premature menopause.
Pelvic ultrasonography showed the presence of an anteflexed uterus, with a normal profile, echostructure and dimensions. Her endometrium had a normal echographic aspect. Both her right and left ovary were normal with respect to dimension and form, without any liquid effusion. A hysterosalpingogram confirmed the normal uterus-tubal anatomy.
Thyroid-stimulating hormone (mIU/mL)
0.40 to 4.50
Free tri-iodothyronine (pg/mL)
2.30 to 5.10
Free thyroxin (ng/dL)
0.80 to 2.00
Anti-thyroid peroxidase antibodies (IU/mL)
Anti- thyroglobulin antibodies (IU/mL)
9 to 72
Follicle-stimulating hormone (IU/L)
Luteinizing hormone (IU/L)
0.1 to 1.0
1.1 to 3.1
BAC clones used for fluorescent in situ hybridization with its location on the X chromosome
To assess whether this was a de novo or a segregating chromosomal abnormality, we studied the karyotype of both parents. Their karyotypes were normal, implying that the chromosomal abnormality was de novo. Furthermore, our patient did not present clinical manifestations associated with X-linked recessive diseases.
X-autosome translocations are extremely rare (one in 30,000). In women, one of the X chromosomes is inactive, and this inactivation is completely random. This phenomenon is called lyonization. In cases of X-autosome translocation, the inactivation is not random but involves the none-translocated X chromosome[9, 10].
We must consider that the X-inactivation center in the Xq13 area is turned off in the translocated chromosome, and different genes, which are important for the development and/or the functionality of the ovary, are present on the long arm of chromosome X.We can assume that X-autosome translocations do not interrupt the genes involved in ovarian functionality, but that they cause altered expression, because of their ‘position effect’.
In females with an active X chromosome translocated in all cells and with the breakpoint not interrupting any functional gene, about half have ovarian failure (breakpoints within the Xq13 to q26 region) and the other half have a normal phenotype (breakpoints outside the Xq13 to q26 region)[13–15].
The purpose of this therapy was not only to intervene in her climacteric symptoms, but to realize at the same time primary and/or secondary prevention of osteoporosis, cardiovascular pathology and cerebral involutional pathologies.
Our study has underlined that karyotyping is one of the fundamental investigations in the evaluation of amenorrhea. It has highlighted a genetic etiology for amenorrhea in the form of a chromosomal abnormality.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Nelson LM: Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009, 360 (6): 606-614. 10.1056/NEJMcp0808697.View ArticlePubMedPubMed CentralGoogle Scholar
- Massin N, Meduri G, Bachelot A, Misrahi M, Kuttenn F, Touraine P: Evaluation of different markers of the ovarian reserve in patients presenting with premature ovarian failure. Mol Cell Endocrinol. 2008, 282 (1–2): 95-100.View ArticlePubMedGoogle Scholar
- Massin N, Czernichow C, Thibaud E, Kuttenn F, Polak M, Touraine P: Idiopathic premature ovarian failure in 63 young women. Horm Res. 2006, 65 (2): 89-95. 10.1159/000091177.View ArticlePubMedGoogle Scholar
- Aittomäki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehväslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A: Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995, 82 (6): 959-968. 10.1016/0092-8674(95)90275-9.View ArticlePubMedGoogle Scholar
- Dragojević-Dikić S, Marisavljević D, Mitrović A, Dikić S, Jovanović T, Janković-Raznatović S: An immunological insight into premature ovarian failure (POF). Autoimmun Rev. 2010, 9 (11): 771-774. 10.1016/j.autrev.2010.06.008.View ArticlePubMedGoogle Scholar
- Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, Al-Inany HG, Falcone T: Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril. 2011, 95 (3): 906-914. 10.1016/j.fertnstert.2010.11.017.View ArticlePubMedGoogle Scholar
- Vujovic S: Aetiology of premature ovarian failure. Menopause Int. 2009, 15 (2): 72-75. 10.1258/mi.2009.009020.PubMedGoogle Scholar
- Human (Homo sapiens) Genome Browser Gateway.http://genome.ucsc.edu/cgi-bin/hgGateway?db=hg18,
- Cottrell CE, Sommer A, Wenger GD, Bullard S, Busch T, Nash Krahn K, Lidral AC, Gastier-Foster JM: Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy. Am J Med Genet A. 2009, 149A (3): 408-414. 10.1002/ajmg.a.32699.View ArticlePubMedPubMed CentralGoogle Scholar
- Schmidt M, Du Sart D: Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X-autosome translocations: a review of 122 cases. Am J Med Genet. 1992, 42 (2): 161-169. 10.1002/ajmg.1320420205.View ArticlePubMedGoogle Scholar
- Wolff DJ, Schwartz S, Carrel L: Molecular determination of X inactivation pattern correlates with phenotype in women with a structurally abnormal X chromosome. Genet Med. 2000, 2 (2): 136-141. 10.1097/00125817-200003000-00004.View ArticlePubMedGoogle Scholar
- Baronchelli S, Villa N, Redaelli S, Lissoni S, Saccheri F, Panzeri E, Conconi D, Bentivegna A, Crosti F, Sala E, Bertola F, Marozzi A, Pedicini A, Ventruto M, Police MA, Dalprà L: Investigating the role of X chromosome breakpoints in premature ovarian failure. Mol Cyto Genet. 2012, 5 (1): 32-Google Scholar
- Layman L: Human gene mutations causing infertility. J Med Genet. 2002, 39 (3): 153-161. 10.1136/jmg.39.3.153.View ArticlePubMedPubMed CentralGoogle Scholar
- Rizzolio F, Sala C, Alboresi S, Bione S, Gilli S, Goegan M, Pramparo T, Zuffardi O, Toniolo D: Epigenetic control of the critical region for premature ovarian failure on autosomal genes translocated to the X chromosome: a hypothesis. Hum Genet. 2007, 121 (3–4): 441-450.View ArticlePubMedGoogle Scholar
- Schlessinger D, Herrera L, Crisponi L, Mumm S, Percesepe A, Pellegrini M, Pilia G, Forabosco A: Genes and translocations involved in POF. Am J Med Genet. 2002, 111 (3): 328-333. 10.1002/ajmg.10565.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.