Endocrine Abstracts

Premature ovarian insufficiency (POI) is a disorder in which amenorrhea, associated to elevated levels of gonadotropins, occurs before the age of 40 years.

The proband, a 36-year-old woman, was born at term after an uneventful pregnancy and delivery from healthy non-consanguineous parents. Growth and mental developmental milestones were normal. At the age of 12 years she presented menarche followed by regular menses, she had no miscarriage and had a successful pregnancy at the age of 27 years. At 35 years of age she experienced asymptomatic abrupt amenorrhea. Physical examination was unremarkable with no evidence of major malformations as well as facial dysmorphisms. Hormonal profile was normal except for LH and FSH values that were in the menopausal range (55.0 and 166.4 mU/ml respectively) and were confirmed over a period of one year.

Environmental, metabolic, iatrogenic and autoimmune causes of POI were excluded. FRAXA expansion was analyzed by standard methods and excluded.

Cytogenetic analyses showed the presence of a supernumerary marker chromosome (SMC) that was characterized by FISH and array-CGH (comparative genomic hybridization).

This marker chromosome derived from chromosome 15 and contained only heterochromatic material. The Prader Willi/Angelman region, that is associated with an abnormal phenotype, was not present. Patients with invdup(15) chromosomes with only the heterochromatin of the proximal 15q have a normal phenotype. Interestingly, an aspect that is sometimes overlooked in these cases is infertility and amenorrhea that is also described in cases with SMC derived by other acrocentric chromosomes and aneuploidies (trisomy 13, 18, 21 and 45,X0).

This case constitutes a further example that etiology of POI is not always associated with a defective gene, but in some cases oocytes atresia can be the consequence of the abnormal meiotic pairing of chromosomes.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.