Abstract
This chapter describes the principles of genetic counselling for families with a child with a DSD, with specific details for the more well-known variations.
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Notes
- 1.
In this chapter, the term ‘risk’ is used in the context of the likelihood of a child of having a disorder/difference of sex development (DSD), but this term may not be appropriate in all clinical situations. In particular, when a particular DSD is viewed as a variation rather than a condition, terms such as ‘chance’ or ‘likelihood’ may be more appropriate. It is important to check in with parents to ensure they are comfortable with the language.
References
Abbas N, McElreavey K, Leconiat M, et al. Familial case of 46,XX male and 46,XX true hermaphrodite associated with a paternal-derived SRY-bearing X chromosome. C R Acad Sci III. 1993;316(4):375–83.
Abir R, Fisch B, Nahum R, et al. Turner's syndrome and fertility: current status and possible putative prospects. Hum Reprod Update. 2001;7(6):603–10.
Allera A, Herbst MA, Griffin JE, et al. Mutations of the androgen receptor coding sequence are infrequent in patients with isolated hypospadias. J Clin Endocrinol Metab. 1995;80(9):2697–9.
Amor D, Delatycki MB, Susman M, et al. 46,XX/46,XY at amniocentesis in a fetus with true hermaphroditism. J Med Genet. 1999;36(11):866–9.
Barbaro M, Oscarson M, Schoumans J, et al. Isolated 46,XY gonadal dysgenesis in two sisters caused by a Xp21.2 interstitial duplication containing the DAX1 gene. J Clin Endocrinol Metab. 2007;92(8):3305–13.
Baxter RM, Arboleda VA, Lee H, et al. Exome sequencing for the diagnosis of 46,XY disorders of sex development. J Clin Endocrinol Metab. 2015;100(2):E333–44.
Bernard V, Donadille B, Zenaty D, et al. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod. 2016;31(4):782–8.
Biason-Lauber A, Konrad D, Meyer M, et al. Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene. Am J Hum Genet. 2009;84(5):658–63.
Blair J, Tolmie J, Hollman AS, et al. Phenotype, ovarian function, and growth in patients with 45,X/47,XXX Turner mosaicism: implications for prenatal counseling and estrogen therapy at puberty. J Pediatr. 2001;139(5):724–8.
Bodri D, Vernaeve V, Figueras F, et al. Oocyte donation in patients with Turner's syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy. Hum Reprod. 2006;21(3):829–32.
Boehmer AL, Brinkmann AO, Niermeijer MF, et al. Germ-line and somatic mosaicism in the androgen insensitivity syndrome: implications for genetic counseling. Am J Hum Genet. 1997;60(4):1003–6.
Bourne H, Stern K, Clarke G, et al. Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47,XXY Klinefelter’s syndrome. Hum Reprod. 1997;12(11):2447–50.
Cameron FJ, Hageman RM, Cooke-Yarborough C, et al. A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal. Hum Mol Genet. 1996;5(10):1625–30.
Canto P, Soderlund D, Reyes E, et al. Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab. 2004;89(9):4480–3.
Cox JJ, Willatt L, Homfray T, et al. A SOX9 duplication and familial 46,XX developmental testicular disorder. N Engl J Med. 2011;364(1):91–3.
Czeizel A, Erodi E, Toth J. Genetics of undescended testis. J Urol. 1981;126(4):528–9.
Dauwerse JG, Hansson KB, Brouwers AA, et al. An XX male with the sex-determining region Y gene inserted in the long arm of chromosome 16. Fertil Steril. 2006;86(2):463.e461–5.
Deeb A, Mason C, Lee YS, et al. Correlation between genotype, phenotype and sex of rearing in 111 patients with partial androgen insensitivity syndrome. Clin Endocrinol. 2005;63(1):56–62.
Doger E, Cakiroglu Y, Ceylan Y, et al. Reproductive and obstetric outcomes in mosaic Turner's syndrome: a cross-sectional study and review of the literature. Reprod Biol Endocrinol. 2015;13:59.
Duncan PA, Shapiro LR, Stangel JJ, et al. The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J Pediatr. 1979;95(3):399–402.
Ferguson-Smith MA, Cooke A, Affara NA, et al. Genotype-phenotype correlations in XX males and their bearing on current theories of sex determination. Hum Genet. 1990;84(2):198–202.
Ferlin A, Garolla A, Foresta C. Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities. Cytogenet Genome Res. 2005;111(3–4):310–6.
Fukami M, Wada Y, Miyabayashi K, et al. CXorf6 is a causative gene for hypospadias. Nat Genet. 2006;38(12):1369–71.
Fullerton G, Hamilton M, Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009? Hum Reprod. 2010;25:588–97.
Gardner RJM, Amor DJ. Gardner and Sutherland’s chromosome abnormalities and genetic counseling. New York: Oxford University Press; 2018.
Gies I, Oates R, De Schepper J, et al. Testicular biopsy and cryopreservation for fertility preservation of prepubertal boys with Klinefelter syndrome: a pro/con debate. Fertil Steril. 2016;105(2):249–55.
Gottlieb B, Trifiro MA. Androgen insensitivity syndrome. GeneReviews®. 2017. doi: NBK1429 [book accession].
Grinspon RP, Rey RA. Disorders of sex development with testicular differentiation in SRY-negative 46,XX individuals: clinical and genetic aspects. Sex Dev. 2016;10(1):1–11.
Guerrier D, Mouchel T, Pasquier L, et al. The Mayer-Rokitansky-Kuster-Hauser syndrome (congenital absence of uterus and vagina)—phenotypic manifestations and genetic approaches. J Negat Results Biomed. 2006;5:1.
Hall H, Hunt P, Hassold T. Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr Opin Genet Dev. 2006;16(3):323–9.
Hanson L, Bryman I, Barrenas ML, et al. Genetic analysis of mosaicism in 53 women with Turner syndrome. Hereditas. 2001;134(2):153–9.
Harper P. Practical genetic counselling. Oxford: Oxford University Press; 2010.
Hiort O, Sinnecker GH, Holterhus PM, et al. Inherited and de novo androgen receptor gene mutations: investigation of single-case families. J Pediatr. 1998;132(6):939–43.
Juul A, Aksglaede L, Lund AM, et al. Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene: case report. Hum Reprod. 2007;22(7):1907–11.
Kajii T, Ferrier A, Niikawa N, et al. Anatomic and chromosomal anomalies in 639 spontaneous abortuses. Hum Genet. 1980;55(1):87–98.
Lachlan KL, Youings S, Costa T, et al. A clinical and molecular study of 26 females with Xp deletions with special emphasis on inherited deletions. Hum Genet. 2006;118(5):640–51.
Laron Z, Dickerman Z, Zamir R, et al. Paternity in Klinefelter’s syndrome—a case report. Arch Androl. 1982;8(2):149–51.
Ledig S, Hiort O, Scherer G, et al. Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal dysgenesis: evaluation of array CGH as diagnostic tool and search for new candidate loci. Hum Reprod. 2010;25(10):2637–46.
Levron J, Aviram-Goldring A, Madgar I, et al. Sperm chromosome analysis and outcome of IVF in patients with non-mosaic Klinefelter’s syndrome. Fertil Steril. 2000;74(5):925–9.
Michala L, Goswami D, Creighton SM, et al. Swyer syndrome: presentation and outcomes. BJOG. 2008;115(6):737–41.
Modi DN, Sane S, Bhartiya D. Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Mol Hum Reprod. 2003;9(4):219–25.
Mortensen KH, Rohde MD, Uldbjerg N, et al. Repeated spontaneous pregnancies in 45,X Turner syndrome. Obstet Gynecol. 2010;115(2 Pt 2):446–9.
Mucke J, Happle R, Theile H. MIDAS syndrome respectively MLS syndrome: a separate entity rather than a particular lyonization pattern of the gene causing Goltz syndrome. Am J Med Genet. 1995;57(1):117–8.
Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991;87(1):81–3.
Oktay K, Bedoschi G, Berkowitz K, et al. Fertility preservation in women with Turner syndrome: a comprehensive review and practical guidelines. J Pediatr Adolesc Gynecol. 2016;29(5):409–16.
Ortenberg J, Oddoux C, Craver R, et al. SRY gene expression in the ovotestes of XX true hermaphrodites. J Urol. 2002;167(4):1828–31.
Palermo GD, Colombero LT, Hariprashad JJ, et al. Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI. Hum Reprod. 2002;17(3):570–5.
Parma P, Radi O, Vidal V, et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet. 2006;38(11):1304–9.
Pasquino AM, Passeri F, Pucarelli I, et al. Spontaneous pubertal development in Turner’s syndrome. Italian Study Group for Turner’s Syndrome. J Clin Endocrinol Metab. 1997;82(6):1810–3.
Pearlman A, Loke J, Le Caignec C, et al. Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am J Hum Genet. 2010;87(6):898–904.
Philibert P, Leprieur E, Zenaty D, et al. Steroidogenic factor-1 (SF-1) gene mutation as a frequent cause of primary amenorrhea in 46,XY female adolescents with low testosterone concentration. Reprod Biol Endocrinol. 2010;8:28.
Queipo G, Zenteno JC, Pena R, et al. Molecular analysis in true hermaphroditism: demonstration of low-level hidden mosaicism for Y-derived sequences in 46,XX cases. Hum Genet. 2002;111(3):278–83.
Queralt R, Madrigal I, Vallecillos MA, et al. Atypical XX male with the SRY gene located at the long arm of chromosome 1 and a 1qter microdeletion. Am J Med Genet A. 2008;146A(10):1335–40.
Ramos ES, Moreira-Filho CA, Vicente YA, et al. SRY-negative true hermaphrodites and an XX male in two generations of the same family. Hum Genet. 1996;97(5):596–8.
Rives N, Joly G, Machy A, et al. Assessment of sex chromosome aneuploidy in sperm nuclei from 47,XXY and 46,XY/47,XXY males: comparison with fertile and infertile males with normal karyotype. Mol Hum Reprod. 2000;6(2):107–12.
Ron-El R, Strassburger D, Gelman-Kohan S, et al. A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter’s syndrome: case report. Hum Reprod. 2000;15(8):1804–6.
Seeherunvong T, Perera EM, Bao Y, et al. 46,XX sex reversal with partial duplication of chromosome arm 22q. Am J Med Genet A. 2004;127A(2):149–51.
Seo JT, Park YS, Lee JS. Successful testicular sperm extraction in Korean Klinefelter syndrome. Urology. 2004;64(6):1208–11.
Slaney SF, Chalmers IJ, Affara NA, et al. An autosomal or X linked mutation results in true hermaphrodites and 46,XX males in the same family. J Med Genet. 1998;35(1):17–22.
Smyk M, Obersztyn E, Nowakowska B, et al. Recurrent SOX9 deletion campomelic dysplasia due to somatic mosaicism in the father. Am J Med Genet A. 2007;143A(8):866–70.
Staessen C, Tournaye H, Van Assche E, et al. PGD in 47,XXY Klinefelter’s syndrome patients. Hum Reprod Update. 2003;9(4):319–30.
Stochholm K, Juul S, Juel K, et al. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006;91(10):3897–902.
Sybert VP. Phenotypic effects of mosaicism for a 47,XXX cell line in Turner syndrome. J Med Genet. 2002;39(3):217–20.
Tarani L, Lampariello S, Raguso G, et al. Pregnancy in patients with Turner’s syndrome: six new cases and review of literature. Gynecol Endocrinol. 1998;12(2):83–7.
Telvi L, Lebbar A, Del Pino O, et al. 45,X/46,XY mosaicism: report of 27 cases. Pediatrics. 1999;104(2 Pt 1):304–8.
Terzoli G, Lalatta F, Lobbiani A, et al. Fertility in a 47,XXY patient: assessment of biological paternity by deoxyribonucleic acid fingerprinting. Fertil Steril. 1992;58(4):821–2.
Trujillo-Tiebas MJ, Gonzalez-Gonzalez C, Lorda-Sanchez I, et al. Prenatal diagnosis of 46,XX male fetus. J Assist Reprod Genet. 2006;23(5):253–4.
Uehara S, Yaegashi N, Maeda T, et al. Risk of recurrence of fetal chromosomal aberrations: analysis of trisomy 21, trisomy 18, trisomy 13, and 45,X in 1,076 Japanese mothers. J Obstet Gynaecol Res. 1999;25(6):373–9.
Wang I, Weil D, Levilliers J, et al. Prevalence and molecular analysis of two hot spots for ectopic recombination leading to XX maleness. Genomics. 1995;28(1):52–8.
Weil D, Wang I, Dietrich A, et al. Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness. Nat Genet. 1994;7(3):414–9.
Woods CG, Noble J, Falconer AR. A study of brothers with Klinefelter syndrome. J Med Genet. 1997;34(8):702.
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Amor, D. (2020). Genetic Counselling. In: Hutson, J., Grover, S., O'Connell, M., Bouty, A., Hanna, C. (eds) Disorders|Differences of Sex Development. Springer, Singapore. https://doi.org/10.1007/978-981-13-7864-5_21
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DOI: https://doi.org/10.1007/978-981-13-7864-5_21
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