Endocrine Abstracts

Recent advancements in genetic testing have revealed various X-chromosome abnormalities as causative factors for both familial and sporadic cases of Primary Ovarian Insufficiency (POI). In this case report, we present an intriguing instance of POI associated with a deletion in the critical region-1 on the long arm of the X-chromosome A 12.5-year-old girl of South Asian descent presented with 8 month history of irregular menstrual periods with bleeding lasting for 10 days and a cycle length of approximately 24 days. She had attained menarche at the age of 9 and there was no notable past medical history or fertility issues in her family members. Examination revealed her weight to be 62.6 kg (98th percentile), height 157.5 cm (75th percentile), and BMI 25.2 kg/m². She was in well-established puberty and had no dysmorphic features, hirsutism, or acanthosis nigricans. Investigations were in keeping with POI (FSH – 54 IU/L, LH – 20 IU/L, 17-Beta Oestradiol < 70 pmol/L). Ultrasound examination showed a normally developed uterus measuring 38 mm in length but with a very thin endometrium. Both ovaries had a volume of 5.9 cc, but no developing follicles. Ovarian antibodies were not detected. Other investigations (Prolactin, TSH, 17-OHP, Coeliac screen) were all normal. AMH was low at <0.2 pmol/L. Array comparative genomic hybridization (array CGH) revealed two X-linked copy number variants 46, X, der(X)(pter->q27.2::p21.1->pter) – arr[hg19]Xp22.33p21.1x3, Xq27.2q28x1. The patient exhibited duplicated genetic material (31.3 Mb terminal gain) on the short arm and a 13.4 Mb terminal deletion on the long arm of one of her X chromosomes. This abnormality was not identified on array CGH of either of patient’s parents. Our patient does not fit the classification of Turner syndrome due to the absence of Xp monosomy. She has a deletion within the critical region-1 (Xq26-q28, POI 1) on one of her X-chromosomes and this is likely to be a significant contributing factor to her POI. The deleted region encompasses 248 genes, many of which are considered crucial for normal ovarian function, however our understanding of the precise mechanism by which this region contributes to POI remains limited.