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Licensed Unlicensed Requires Authentication Published by De Gruyter November 8, 2016

A case of 46,XX dysgenesis and marked tall stature; the need for caution in interpreting array comparative genomic hybridization (CGH)

Vidya Kanamkote Narayanan, Mira Kharbanda and Malcolm Donaldson

Abstract

Background:

Gonadal dysgenesis with an apparently normal 46,XX karyotype is a rare cause of hypergonadotrophic hypogonadism. Tall stature is not a widely recognized association.

Case report:

A 15-year-old girl presented with primary amenorrhoea. Examination showed a non-dysmorphic girl of normal intellect with no breast development (Tanner stage B1P4A1) who was tall compared with her parents: height standard deviation score (SDS) +1.56 vs. midparental height of +0.23 SDS, and slim build (weight −0.13 SDS). Investigations showed a 46,XX karyotype, elevated gonadotropins (FSH 119 and LH 33.7 IU/L), serum estradiol <5 pmol/L, uterine length 3.75 cm with cylindrical shape, and absent ovaries on ultrasound. Initially, a 364055-bp deletion on Xp21.2 was reported on array CGH. However, repeat analysis using BlueGnome CytoChip ISCA 4x180k v2.0 array was normal. With oral ethinyl estradiol induction puberty progressed to B4P4A2 but aged 18.4 years, the patient was remarkably tall with height SDS +2.88, weight SDS +0.97.

Conclusions:

Caution is needed in interpreting small changes with array CGH, particularly with the older assays. We postulate that the genetic change causing 46,XX gonadal dysgenesis in our patient may have also resulted in unsuppressed somatic growth. More critical height assessment, including parental height measurement, of future patients with 46,XX gonadal dysgenesis is recommended in order to determine whether or not a true association with tall stature may be present in certain cases.


Dedication to: This report is dedicated to the memory of our dear friend and colleague Dr. John Tolmie, Clinical Geneticist who died on 30 March 2014 while climbing the mountain Ben Nevis in Scotland.



Corresponding author: Dr. Malcolm Donaldson, Section of Child Health, Glasgow University School of Medicine, c/o Royal Hospital for Children, Queen Elizabeth University Hospital, Govan Road, Glasgow, G51 4TF, UK, Phone: +0141 451 6531, Fax: 0141 201 2215

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Goswami D, Conway GS. Premature ovarian failure. Horm Res 2007;68:196–202.10.1159/000102537Search in Google Scholar

2. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol 1986;67:604–6.10.1097/00006254-198703000-00020Search in Google Scholar

3. Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update 2005;11:391–410.10.1093/humupd/dmi012Search in Google Scholar

4. Conway GS, Kaltsas G, Patel A, Davies MC, Jacobs HS. Characterization of idiopathic premature ovarian failure. Fertil Steril 1996;64:337–41.10.1016/S0015-0282(16)58095-9Search in Google Scholar

5. Vegetti W, Grazia Tibiletti M, Testa G, de Lauretis Y, Alagna F, et al. Inheritance in idiopathic premature ovarian failure: analysis of 71 cases. Hum Reprod 1998;13:1796–800.10.1093/humrep/13.7.1796Search in Google Scholar

6. Bath LE, Critchley HO, Chambers SE, Anderson RA, Kelnar CJ, et al. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol 1999;106:1265–72.10.1111/j.1471-0528.1999.tb08180.xSearch in Google Scholar

7. Ogata T, Hasegawa T, Tamai S, Sato S, Hasegawa Y, et al. Hypergonadotropic hypogonadism in a 3-year-old girl with blepharophimosis, ptosis, and epicanthus inversus syndrome. Horm Res 1998;50:190–2.10.1159/000023272Search in Google Scholar

8. Bösze P, Skripeczky K, Gaál M, Tóth A, László J. Perrault’s syndrome in two sisters. Am J Med Genet 1983;16:237–41.10.1002/ajmg.1320160213Search in Google Scholar

9. Nakamura Y, Suehiro Y, Sugino N, Sasaki K, Kato H. A case of 46,X,der(X) (pter→q21::p21→pter) with gonadal dysgenesis, tall stature and endometriosis. Fertil Steril 2001;75:1224–5.10.1016/S0015-0282(01)01807-6Search in Google Scholar

10. Freeman JV, Cole TJ, Chinn S, Jones PR, White EM, et al. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995;73:17–24.10.1136/adc.73.1.17Search in Google Scholar PubMed PubMed Central

11. Tanner, JM. Growth at adolescence, 2nd ed. Oxford; Blackwell Scientific, 1962.Search in Google Scholar

12. Tanner JM, Whitehouse RH, Cameron N, Marshall WA, Healy MJ, et al. Assessment of skeletal maturity and prediction of adult height (TW2 method). 2nd ed. London: Academic Press, 1983.Search in Google Scholar

13. Gault EJ, Perry RJ, Cole TJ, Casey S, Paterson WF, et al. British society for paediatric endocrinology and diabetes: effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial. Br Med J 2011;342:d1980.10.1136/bmj.d1980Search in Google Scholar PubMed PubMed Central

14. Cordts EB, Christofolini DM, dos Santos AA, Bianco B, Barbosa CP. Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet 2011;283:635–43.10.1007/s00404-010-1815-4Search in Google Scholar PubMed

15. Sybert PV, McCauley E. Turner’s syndrome. N Engl J Med 2004;351:1227–38.10.1056/NEJMra030360Search in Google Scholar PubMed

16. Schlessinger D, Herrera L, Crisponi L, Mumm S, Percesepe A, et al. Genes and translocations involved in POF. Am J Med Genet 2002;111:328–33.10.1002/ajmg.10565Search in Google Scholar PubMed

17. Kenneson A, Cramer DW, Warren ST. Fragile X premutations are not a major cause of early menopause. Am J Hum Genet 1997;61:1362–9.10.1086/301647Search in Google Scholar PubMed PubMed Central

18. Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis 2006;1:9.10.1186/1750-1172-1-9Search in Google Scholar PubMed PubMed Central

19. Pouresmaeili F, Fazelli Z. Premature ovarian failure: a critical condition in the reproductive potential with various genetic causes. Int J Fertil Steril 2014;8:1–12.Search in Google Scholar

20. Therman E, Laxova R, Susman B. The critical region on the human Xq. Hum Genet 1990;85:455–61.10.1007/BF00194216Search in Google Scholar PubMed

21. Rizzolio F, Bione S, Sala C, Goegan M, Gentile M, et al. Chromosomal rearrangements in Xq and premature ovarian failure: mappingof 25 new cases and review of the literature. Hum Reprod 2006;21:1477–83.10.1093/humrep/dei495Search in Google Scholar PubMed

22. Sala C, Arrigo G, Torri G, Martinazzi F, Riva P, et al. Eleven X chromosome breakpoints associated with premature ovarian failure (POF) map to a 15-Mb YAC contig spanning Xq21. Genomics 1997;40:123–31.10.1006/geno.1996.4542Search in Google Scholar PubMed

23. Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, et al. A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J Hum Genet 1998;62:533–41.10.1086/301761Search in Google Scholar PubMed PubMed Central

24. Prueitt RL, Ross JL, Zinn AR. Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP1 as a premature ovarian failure candidate gene. Cytogenet Cell Genet 2000;89:44–50.10.1159/000015560Search in Google Scholar PubMed

25. Bione S, Rizzolio F, Sala C, Ricotti R, Goegan M, et al. Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B. Hum Reprod 2004;19:2759–66.10.1093/humrep/deh502Search in Google Scholar PubMed

26. Prueitt RL, Chen H, Barnes RI, Zinn AR. Most X;autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Cytogenet Genome Res 2002;97:32–8.10.1159/000064052Search in Google Scholar PubMed

27. van Bokhoven H, van Genderen C, Ropers HH, Cremers FP. Dinucleotide repeat polymorphism within the choroideremia gene at Xq21.2. Hum Mol Genet 1994;3:1446.10.1093/hmg/3.8.1446Search in Google Scholar PubMed

28. Iossa S, Costa V, Corvino V, Auletta G, Barruffo L, et al. Phenotypic and genetic characterization of a family carrying two Xq21-21.3 interstitial deletions with syndromic hearing loss. Molecular Cytogenetics 2015;8:18.10.1186/s13039-015-0120-0Search in Google Scholar PubMed PubMed Central

29. Tartaglia R, Howell S, Sutherland A, Wilson R, Wilson L. A review of trisomy X (47,XXX). Orpha J Rare Dis 2010;5:8. doi:10.1186/1750-1172-5-8.Search in Google Scholar PubMed PubMed Central

30. Fernandez R, Pasaro E. Tall stature and gonadal dysgenesis in a non-mosaic girl 45,X. Horm Res Paediatr 2010;73:210–4.10.1159/000284364Search in Google Scholar PubMed

Received: 2016-5-10
Accepted: 2016-10-5
Published Online: 2016-11-8
Published in Print: 2016-12-1

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