Ovarian dysgenesis with balanced autosomal translocation.
MS Tullu, P Arora, RC Parmar, MN Muranjan, BA Bharucha
Genetics Division, Department of Paediatrics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai - 400 012, India. , India
M S Tullu
Genetics Division, Department of Paediatrics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai - 400 012, India.
Autosomal translocations are rare in the patients with ovarian dysgenesis. An 18-year-old female who presented with primary amenorrhoea had hypergonadotropic hypogonadism and streak ovaries with hypoplastic uterus. Karyotype analysis revealed a balanced autosomal translocation involving chromosomes 1 and 11. The probable role of autosomal translocations in ovarian dysgenesis has been discussed.
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Tullu M S, Arora P, Parmar R C, Muranjan M N, Bharucha B A. Ovarian dysgenesis with balanced autosomal translocation. J Postgrad Med 2001;47:113-5
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Tullu M S, Arora P, Parmar R C, Muranjan M N, Bharucha B A. Ovarian dysgenesis with balanced autosomal translocation. J Postgrad Med [serial online] 2001 [cited 2022 Aug 11 ];47:113-5
Available from: https://www.jpgmonline.com/text.asp?2001/47/2/113/216
Chromosomal translocations have been reported in a number of women undergoing cytogenetic studies for primary amenorrhoea and gonadal dysgenesis. Most of these have been translocations between the X chromosome and an autosome. The autosomes involved have been 4, 6, 9, 12, 15 and 18.,,,,, Autosomal translocation associated with ovarian failure is a rarity and only two such cases have been reported in literature. These cases had ovarian dysgenesis. We report a case of primary amenorrhoea due to ovarian dysgenesis with a unique balanced autosomal translocation.
An 18-year-old female was referred to the Genetic clinic for primary amenorrhoea. There was no history of systemic illness in the patient. She was a product of non-consanguineous marriage and there was no family history of pubertal delay. On general examination, there were no features of Turner syndrome and the anthropometric measurements were normal. She had attained Tanner Stage 2 of sexual maturity rating.
Relevant laboratory investigations revealed a normal complete blood count, normal prolactin level (7 ng/ml; normal: 3-25 ng/ml), high follicle-stimulating hormone level (>150 mIU/ml; normal: 10-15 mIU/ml), and a high luteinising hormone level (90 mIU/ml; normal: 10-15 mIU/ml). These investigations were suggestive of hypergonadotropic hypogonadism. Ultrasound examination of the pelvis showed streak ovaries with hypoplastic uterus (measuring 4.6 x 1.9 x 1.3 cm). Karyotype analysis of 100 metaphases using standard ‘G’-banding technique revealed a pattern of 46, XX, t (1;11) (q31;q25) suggestive of a balanced autosomal translocation involving the long arms of chromosomes 1 and 11 [Figure:1].
The patient was referred to gynaecologist and endocrinologist but did not follow-up further.
Chromosomal aberrations are the commonest cause of primary amenorrhoea. Majority of the aberrations are due to the Turner syndrome and its variants (such as deletions of the X chromosome, isochromosome X and ring chromosome X). In an attempt to correlate the phenotypic variations in Turner syndrome, it was proposed that deletions of the short arm result in short stature with the Turner phenotype whereas the deletions of the long arm of one of the X chromosomes in the q13-q27 band leads to failure of ovarian development. This was further illustrated by a number of cases involving X-autosomal translocations having primary amenorrhoea with gonadal dysgenesis but without the Turner phenotype. This led to the designation of a critical region on the long arm of the X-chromosome spanning the q13 to q26 bands., Disruption between these points leads to gonadal dysgenesis. A point to note is the association of male sterility and azoospermia with X-autosomal translocations with the break points beyond the critical region of Xq., However, the Xq critical region hypothesis fails to explain the isolated case reports of autosomal translocation in women evaluated for amenorrhoea and gonadal dysgenesis. Tupler et al have reported two unrelated women with gonadal dysgenesis who were found to have balanced autosomal translocations i.e. t (6;15) (p21.3;q15) and t (8;9) (p11.2;q12) respectively. Ours is the third case to be reported. The enigma of gonadal dysgenesis in such cases could possibly be attributed to the presence of autosomal gene(s) playing a role in the normal gonadal development. Animal studies have shown that oocyte degeneration can occur with balanced autosomal translocations. Though reports of structural autosomal abnormalities in human menstrual and reproductive failure are few and far apart, they cannot be brushed off as merely co-incidental. Interestingly, Kucheria et al have described two unrelated girls with a normal female body habitus and amenorrhoea as a result of Mullerian agenesis. The chromosomal study revealed an identical pattern of 46, XX, t (12;14) (14q;31q) in both of them . If autosomal translocations were to be considered inconsequential in the three cases reported so far (including our case), the clinical features along with the presence of structurally normal X chromosomes would have favoured a diagnosis of pure gonadal dysgenesis. This condition is rarely evident in a child as there are no physically obvious stigmata.
To summarise, autosomal abnormalities can be associated with gonadal dysgenesis, but in the absence of overwhelming evidence at present, it may be premature to implicate such abnormalities as having an aetiological role.
The authors thank Mrs. Seema Sharma (MSc; Scientific Officer, KEM Hospital) for her help in the karyotype analysis of the case reported.
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