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BIRTH DEFECT RISK FACTOR SERIES: Klinefelter Syndrome

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Definition

Klinefelter syndrome was first described in 1942 as an endocrine disorder (Lanfranco 2004, Klinefelter 1942). However, the chromosomal basis for the syndrome was not reported until 1956 and the exact chromosomal abnormality until 1959 (Arens 1988). As the characteristics of this syndrome can besubtle, it is often not diagnosed until adulthood when the affected individual is examined for fertility problems (Lanfranco 2004).

Klinefelter syndrome is a sex chromosomal abnormality that typically involves the presence of two or more X chromosomes and one Y chromosome; the resulting karyotype (the chromosomal make up of the cell) is 47,XXY. Approximately 80% of Klinefelter cases possess the 47, XXY karyotype (Lanfranco 2004). The residual 20% of cases have higher-grade chromosome aneupolidies (i.e., 48,XXYY) or have chromosomal mosaicism (46, XY/47,XXY) (Lanfranco 2004). Individuals with mosaic-type Klinfelter syndrome have less severe symptoms, and this mosaicism may only be present within the testes while other tissue samples, including blood, display a normal 47, XY karyotype (Lanfranco 2004).

The clinical features of Klinefelter syndrome are subtle and can be variable. Postnatal diagnosis is unlikely to be made in the first decade of life, and many individuals with Klinefelter syndrome may not be diagnosed at all (Abramsky 1997, Nielsen 1984).

Individuals with Klinefelter syndrome are usually physically normal as infants except for the possible presence of minor genital anomalies such as hypospadias and small or undescended testicles (Linden 1996, Schwartz 1991, Buyse 1990, Kleczkowska 1988). Other common minor anomalies associated with Klinefelter syndrome include brachycephaly, low posterior hairline, fifth finger clinodactyly, and simian creases (Buyse 1990).

The features most associated with Klinefelter syndrome typically do not become evidence until adolescence (Buyse 1990). These features include tall stature, small and atrophic testes, and gynecomastia (Linden 1996). Individuals with 47,XXY have variable fertility, depending on the karyotype present and if the individual displays mosaicism (Denschlag 2004, Abramsky 1997, Linden 1996). However, it should be noted that most individuals with Klinefelter syndrome have to resort to assisted reproductive techniques (Denschlag 2004)

Individuals with Klinefelter syndrome usually have normal intelligence although their IQ may be 10-15 points lower than average with verbal IQ less than performance IQ. They also may have speech and language delays, dyslexia, and poor motor coordination (Linden 2002, Abramsky 1997, Linden 1996). Generally, individuals with prenatally diagnosed Klinefelter syndrome have fewer developmental problems than individuals with postnatally diagnosed Klinefelter syndrome (Linden 2002).

Individuals with 47,XXY/46,XY mosaicism are often no different than normal males and may be fertile (Linden 1996). Individuals with more than one additional sex chromosome, particularly X, are likely to have more severe symptoms (Linden 1995).

Table 1 summarizes the karyotypes commonly associated with Klinefelter syndrome. The distribution of the karyotypes from several studies is presented in table 2.

Table 1. Karyotypes commonly associated with Klinefelter syndrome

Karyotype

Description

47,XXY

Extra X chromosome

47,XXY/46,XY

Extra X chromosome mosaic with normal male sex chromosome complement

47,XXY/46,XX

Extra X chromosome mosaic with normal female sex chromosome complement

48,XXYY

Extra X and Y chromosomes

48,XXXY

2 extra X chromosomes

Karyotypes may occur as listed above or as part of mosaicism (when there are cells present in the body that have two different genetic makeup).

Table 2. Proportion (%) of Klinefelter syndrome cases represented by various karyotypes in several studies

Reference

47,XXY

47,XXY/46,XY

47,XXY/46,XX

other

Lanfranco 2004

20

10

NA

NA

Christian 2000

86

11

4

0

Perrotin 2000

79

7

0

14

Nielsen 1991

70

23

0

7

Etiology

Klinefelter syndrome results from nondisjunction (when cells do not divide their chromosomes evenly, so that one cell has two copies of a particular gene and one cell has none), usually in formation of the eggs or sperm, when one of the gametes has an extra X chromosome. Fertilization of an X egg by an XY sperm or an XX egg by a Y sperm would result in a conceptus with Klinefelter syndrome.

There are three mechanisms that can result in a 47, XXY karyotype. These include nondisjunction within the egg (maternal), the sperm (paternal), or an error in the division of the zygote cells after conception (Robinson 1999). Table 3 lists the parental origin of the extra X chromosome from various studies. Because of the presence of the extra chromosome, the meiotic phase where the nondisjunction occurred [meiosis I (MI) or meiosis II (MII)] can be determined. In approximately 55% of the cases of 47,XXY, the extra X chromosome was of maternal origin, and in the majority of these cases the nondisjunction occurred in MI. In approximately 45% of the cases, the X chromosome was of paternal origin, and the nondisjunction was almost always found to have occurred in MI.

Table 3. Parental origin (%) of the X chromosome present in Klinefelter syndrome by various studies

Pregnancy outcome

Maternal

Paternal

 
 

Total

MI

MII

total

MI

MII

Jacobs 1995

54

70

25

46

100

0

Harvey 1990

51

72

28

49

   

Sanger 1977

67

47

20

33

100

0

Lorda-Sanchez 1992

51

50

39

49

100

0

Jacobs 1988

47

72

19

53

100

0

Carothers 1988

58

   

42

   

MacDonald 1994

54

73

27

46

100

0

MI - meiosis I MII - meiosis II Percentages may not total 100% because some origins may be unknown or occur in mitosis.

Several studies have indicated that paternal age has not been reported to influence the paternal origin of Klinefelter syndrome (MacDonald 1994, Harvey 1990, Jacobs 1988). However, it has been shown that older men produce more sperm with aneuploidies (Lanfranco 2004, Lowe 2001). In the exception, increased paternal age was associated with paternal origin of the X chromosome (Lorda-Sanchez 1992). Increased maternal age has been associated with maternal origin of the extra X chromosome in nondisjunction in MI but not MII (Lanfranco 2004, Lorda-Sanchez 1992, Harvey 1990). In cases where there is more than one extra sex chromosome, the extra chromosomes are usually from the same parent (Linden 1995). Parental origin of the extra X chromosome does not appear to affect the clinical features of the individual with Klinefelter syndrome (Lorda-Sanchez 1992, Jacobs 1988).

Prenatal diagnosis

Klinefelter syndrome may be prenatally diagnosed through cytogenetic analysis of cells obtained through such procedures as amniocentesis and chorionic villus sampling.

Fetal sex chromosomal abnormalities (47,XXX, 47,XXY, and 47,XYY) have been associated with increased nuchal translucency, which is the accumulation of fluid in the back of the neck of the fetus which takes place between 11 and 14 weeks. This measurement, combined with the measurement of maternal serum levels of free beta-human chorionic gonadotropin (hCG) and pregnancy-assisted plasma protein-A (PAPP-A) in the first trimester often indicate when the fetus possesses a chromosomal abnormality (Spencer 2000, Sebire 1998).

Elevated second-trimester maternal serum levels of alpha-fetoprotein (Fejgin 1990) and hCG (Barnes-Kedar 1993, Ben-Neriah 1991) have been associated with fetuses with Klinefelter syndrome. However, this association with abnormal second-trimester maternal serum screen is weak, and Klinefelter syndrome is not systematically screened for using maternal serum screening (Ryall 2001).

In addition, fetuses with Klinefelter syndrome typically do not have abnormal ultrasound. Thus cases of Klinefelter syndrome will mostly be prenatally diagnosed incidentally from cytogenetic analysis for other reasons such as advanced maternal age (De Vigan 2001, Abramsky 1997). However, fetal karyotype is not a good indicator of the features or severity of the syndrome. It is difficult to prenatally predict the postnatal outcome of the pregnancy. Quite often, the clinical presentation of the child does not correlate to the cytogenic findings, with the most extreme cases manifesting different genital sex than initially indicated (Pettenait 1991).

EPIDEMIOLOGY AND OUTCOME

Prevalence and pregnancy outcome

The live birth prevalence of Klinefelter syndrome has been reported to be 4.3-15.0 per 10,000 births or 8.4-29.0 male births (Table 4). The Klinefelter syndrome rate is even higher prenatally. One study found the rate at prenatal diagnosis to be 33/10,000 males (Ferguson-Smith 1984). A recent Danish study indicated that Klinfelter syndrome was present in 153 per 100,000 babies tested prenatally (Borjesen 2003).

Klinefelter syndrome may be found among fetal deaths. Studies have reported that Klinefelter syndrome accounts for 0.2% of spontaneous abortions (early fetal deaths) and 0.2-0.4% of stillbirths (late fetal deaths), and 0.08% of all clinically recognized pregnancies. An estimated 53-55% of conceptions affected with Klinefelter syndrome are expected to survive to term (Jacobs 1995, Hassold 1984).

Approximately 5% of Klinefelter syndrome cases detected at amniocentesis resulted in fetal deaths. This is not significantly different from the rate for nonchromosomal fetal deaths (Hook 1989). Thus Klinefelter syndrome does not appear to affect fetal viability (Hook 1989, Ferguson-Smith 1984).

Because of prenatal diagnosis, some Klinefelter syndrome fetuses will be electively terminated (De Vigan 2001) (Table 5). Elective termination rates have been reported to vary by study and by karyotype. Termination rates for 47,XXY are higher than for 47,XXY/46,XY. Differences in termination rates between studies may reflect differences in time periods of the studies or differences in access to and/or use of prenatal diagnosis and elective termination. One study indicated that the type of health professional involved in counseling the parents of fetuses with Klinefelter syndrome has a significant effect on the outcome of the pregnancy. Parents who consulted with a genetic specialist were more likely to continue the pregnancy than those who only spoke with other health care professionals (Marteau 2002).


Table 4. Prevalence per 10,000 births of Klinefelter syndrome

Reference

Location

Time period

Rate

Nielsen 1991

Denmark

1969-1988

8.0, 15.7*

Hansteen 1982

Norway

1978-1979

5.5, 10.5*

Buckton 1980

Scotland

1976-1977

15.0, 29.0*

Friedrich 1975

Denmark

1969-1971

7.9, 15.3*

Hamerton 1975

Canada

1970-1973

4.3, 8.4*

Jacobs 1974

Scotland

1967-1972

9.4, 14.0*

*rate per male births only

Table 5. Termination rates (%) of prenatally diagnosed Klinefelter syndrome cases

Reference

Klinefelter syndrome

47,XXY

47,XXY/46,XY

Marteau 2002

44

   

Chaabouni 2001

67

60

 

Horger 2001

 

0

 

Sagi 2001

 

85

 

Christian 2000

 

88

0

Perrotin 2000

50

45

0

Mansfield 1999 (review)

58 (36-92)

   

Meschede 1998

 

17

0

Verp 1988

 

60

 

Verp 1988 (review)

 

75

 

Holmes-Siedle 1987

 

67

 

Holmes-Siedle 1987 (review)

 

65

 

Nielsen 1984

75

   

Mortality/Survival

The lifespan for Klinefelter syndrome is believed to be normal (Buyse 1990).

The annual report for the birth defects registry in Hawaii reported no cases of Klinefelter syndrome to have died in the first year after delivery (Merz 2000). One investigation reported that the infant mortality rate associated with all sex chromosome abnormalities increased during 1985-1997 (Lee 2001).


DEMOGRAPHIC AND REPRODUCTIVE FACTORS

Sex

By definition, Klinefelter syndrome occurs exclusively among males.

Parental age

Risk of Klinefelter syndrome increases with increasing maternal age (Carothers 1988, Ferguson-Smith 1984, Hook 1983, Hook 1981, Carothers 1978). One investigation found paternal age had no affect on Klinefelter syndrome risk after controlling for maternal age (Carothers 1988). However, one study indicated that there was an increased risk of Klinefelter syndrome with increasing paternal and maternal age, due to an increased likelihood of meiotic nondisjunction within the aging gametes (Lanfranco 2004, Lowe 2001, Robinson 1999).

Race/ethnicity

One study reported increased risk of Klinefelter syndrome among offspring of Vietnamese mothers when compared with offspring of non-Hispanic white mothers in California (Shaw 2002).

Seasonality

One investigation reported higher rates of Klinefelter syndrome in May-July and lower rates in September, October, and December, but this seasonal variation was restricted to deliveries prior to 1946 (Videbach 1984).

Multiple gestation pregnancies

There is increased risk of Klinefelter syndrome in multiple gestation pregnancies (Flannery 1984).

Assisted Reproductive Technology (ART)

Klinefelter syndrome has been reported among infants conceived by intracytoplasmic sperm injection (ICSI) (Aboulghar 2001). For all ART techniques, there have been higher risks for chromosome abnormalities and congenital birth defects. This is likely do to the underlying factors that contributed to infertility as opposed to ART techniques themselves (Hansen 2002).

Diabetes

One investigation reported a higher rate of Klinefelter syndrome with maternal gestational diabetes (Moore 2002).

Folate metabolism enzymes

No association has been reported between 47,XXY and 47,XXX cases and folate metabolism enzymes (Hassold 2001).

REFERENCES

  • Aboulghar H, Aboulghar M, Mansour R, Serour G, Amin Y, Al-Inany H. A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection. Fertil Steril 2001;76:249-253.
  • Abramsky L, Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: Estimated rates of and indication for postnatal diagnosis with implications for prenatal counseling. Prenat Diagn 1997;17:363-368.
  • Arens R, Marcus D, Engelberg S, Findler G, Goodman RM, Passwell JH. Cerebral germinomas and Klinefelter syndrome. A review. Cancer 1988;61:1228-1231.
  • Barnes-Kedar I, Amiel A, Maor O, Fejgin M. Elevated human chorionic gonadotropin levels in pregnancies with sex chromosome abnormalities. Am J Med Genet 1993;45:356-357.
  • Ben-Neriah Z, Anteby E, Zelikoviz B, Bach G. Increased maternal serum human chorionic gonadotropin level associated with Klinefelter's syndrome. Prenat Diagn 1991;11:923-924.
  • Bender B, Fry E, Penningotn B, Puck M, Salbenblatt J, Robinson A. Speech and language development in 41 children with sex chromosome abnormalities. Pediatrics, Vol. 71, No. 2, 1983.
  • Bojesen A, Juul S, Gravholt C. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. Journal of Clinical Endocrinology and Metabolism, 88(2):629-626, 2003.
  • Buckton KE, O'Riordan ML, Ratcliffe S, Slight J, Mitchell M, McBeath S, Keay AJ, Barr D, Short M. A G-band study of chromosomes in liveborn infants. Ann Hum Genet 1980;43:227-239.
  • Buyse ME, ed. Klinefelter syndrome. In: Birth Defects Encyclopedia. Cambridge, Massachusetts: Blackwell Scientific Publications, 1990:1014-1015.
  • Carothers AD, Collyer S, De Mey R, Frackiewicz A. Parental age and birth order in the aetiology of some sex chromosome aneuploidies. Ann Hum Genet 1978;41:277-278.
  • Carothers AD, Filippi G. Klinefelter's syndrome in Sardinia and Scotland. Comparative studies of parental age and other aetiological factors in 47,XXY. Hum Genet 1988;81:71-75.
  • Chaabouni H, Chaabouni M, Maazoul F, M'Rad R, Jemaa LB, Smaoui N, Terras K, Kammoun H, Belghith N, Ridene H, Oueslati B, Zouari F. Prenatal diagnosis of chromosome disorders in Tunisian population. Ann Genet 2001;44:99-104.
  • Christian SM, Koehn D, Pillay R, MacDougall A, Wilson RD. Parental decisions following prenatal diagnosis of sex chromosome aneuploidy: a trend over time. Prenat Diagn 2000;20:37-40.
  • De Vigan C, Baena N, Cariati E, Clementi M, Stoll C; EUROSCAN Working Group. Contribution of ultrasonographic examination to the prenatal detection of chromosomal abnormalities in 19 centres across Europe. Ann Genet 2001;44:209-217.
  • Denschlag D, Tempfer C, Kunze M, Wolff G, Keck C. Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review. Fertility and Sterility, Vol. 82, No. 4, 2004.
  • Fejgin M, Zeitune M, Amiel A, Beyth Y. Elevated maternal serum alpha-fetoprotein level and sex chromosome aneuploidy. Prenat Diagn 1990;10:414-416.
  • Ferguson-Smith MA, Yates JR. Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative European study on 52 965 amniocentesis. Prenat Diagn 1984;4:5-44.
  • Flannery DB, Brown JA, Redwine FO, Winter P, Nance WE. Antenatally detected Klinefelter's syndrome in twins. Acta Genet Med Gemellol (Roma) 1984;33:51-56.
  • Forrester M, Merz R. Pregnancy outcome and prenatal diagnosis of sex chromosome abnormalities in Hawaii, 1986-1999. American Journal of Medical Genetics, 119A:305-310, 2003.
  • Friedrich U, Nielsen J. Chromosome studies in 5,049 consecutive newborn children. Clin Genet 1973;4:333-343.
  • Hamerton JL, Canning N, Ray M, Smith S. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet 1975;8:223-243.
  • Hansen M, Kurinczuk J, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. New England Journal of Medicine, Vol. 346, No. 10, 2002.
  • Hansteen IL, Varslot K, Steen-Johnsen J, Langard S. Cytogenetic screening of a newborn population. Clin Genet 1982;21:309-314.
  • Harvey J, Jacobs PA, Hassold T, Pettay D. The parental origin of 47,XXY males. Birth Defects Orig Artic Ser 1990;26:289-296.
  • Hassold TJ, Burrage LC, Chan ER, Judis LM, Schwartz S, James SJ, Jacobs PA, Thomas NS. Maternal folate polymorphisms and the etiology of human nondisjunction. Am J Hum Genet 2001;69:434-439.
  • Hassold TJ, Jacobs PA. Trisomy in man. Annu Rev Genet 1984;18:69-97.
  • Holmes-Siedle M, Ryynanen M, Lindenbaum RH. Parental decisions regarding termination of pregnancy following prenatal detection of sex chromosome abnormality. Prenat Diagn 1987;7:239-244.
  • Hook EB, Hamerton JL. The frequency of chromosomal abnormalities detected in consecutive newborn studies; differences between studies; results by sex and severity of phenotypic involvement. In: Hook EB, Porter IH, eds. Population Cytogenetics: Studies in Humans. New York: Academic Press 1977:63-79.
  • Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol 1981;58:282-285.
  • Hook EB, Cross PK, Schreinemachers DM. Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA 1983;249:2034-2038.
  • Hook EB, Topol BB, Cross PK. The natural history of cytogenetically abnormal fetuses detected at midtrimester amniocentesis which are not terminated electively: new data and estimates of the excess and relative risk of late fetal death associated with 47,+21 and some other abnormal karyotypes. Am J Hum Genet 1989;45:855-861.
  • Horger EO, Finch H, Vincent VA. A single physician's experience with four thousand six hundred genetic amniocenteses. Am J Obstet Gynecol 2001;185:279-288.
  • Jacobs PA, Melville M, Ratcliffe S, Keay AJ, Syme J. A cytogenetic survey of 11,680 newborn infants. Ann Hum Genet 1974;37:359-376.
  • Jacobs PA, Hassold TJ, Whittington E, Butler G, Collyer S, Keston M, Lee M. Klinefelter's syndrome: an analysis of the origin of the additional sex chromosome using molecular probes. Ann Hum Genet 1988;52:93-109.
  • Jacobs PA, Hassold TJ. The origin of numerical chromosome abnormalities. Adv Genet 1995;33:101-133.
  • Kleczkowska A, Fryns JP, Van den Berghe H. X-chromosome polysomy in the male. The Leuven experience 1966-1987. Hum Genet 1988;80:16-22.
  • Klinefelter HF, Reifenstein EC, Albright F. syndrome characterized by gynecomastia, spermatogenesis without a-leydigism and increased excretion of follicle stimulating hormone. J Clin Endocrinol metabol 1942;2:615-627.
  • Lanfranco F Kamischke A, Zitzman M, Nieschlag E. Klinefelter’s syndrome. The Lancet, Vol. 364, 2004.
  • Lee K, Khoshnood B, Chen L, Wall SN, Cromie WJ, Mittendorf RL. Infant mortality from congenital malformations in the United States, 1970-1997. Obstet Gynecol 2001;98:620-627.
  • Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics 1995;96:672-682.
  • Linden MG, Bender BG, Robinson A. Intrauterine diagnosis of sex chromosome aneuploidy. Obstet Gynecol 1996;87:468-475.
  • Linden MG, Bender BG. Fifty-one prenatally diagnosed children and adolescents with sex chromosome abnormalities. Am J Med Genet 2002;110:11-18.
  • Lorda-Sanchez I, Binkert F, Maechler M, Robinson WP, Schinzel AA. Reduced recombination and paternal age effect in Klinefelter syndrome. Hum Genet 1992;89:524-530.
  • Lowe X, Eskenzai B, Nelson D, Kidd S, Alme A, Wyrobek A. Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome. American Journal of Genetics, 69:1046-1054, 2001.
  • MacDonald M, Hassold T, Harvey J, Wang LH, Morton NE, Jacobs P. The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. Hum Mol Genet 1994;3:1365-1371.
  • Mansfield C, Hopfer S, Marteau TM. Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: A systematic literature review. Prenat Diagn 1999;19:808-812.
  • Marteau TM, Nippert I, Hall S, Limbert C, Reid M, Bobrow M, Cameron A, Cornel M, Van Diem M, Eiben B, Garcia-Minaur S, Goujard J, Kirwan D, McIntosh K, Soothill P, Verschuuren-Bemelmans C, De Vigan C, Walkinshaw S, Abramsky L, Louwen F, Miny P, Horst J. Outcomes of pregnancies diagnosed with Klinefelter syndrome: the possible influence of health professionalsdagger. Prenat Diagn 2002;22:562-566.
  • Merz RD, Forrester MB. Hawaii Birth Defects Program, 1986-1999 Statewide Data, Surveillance Report Number 8 on Birth Defects in Hawaii, January 1, 1986-December 31, 1999, December 2000, 1-126.
  • Meschede D, Louwen F, Nippert I, Holzgreve W, Miny P, Horst J. Low rates of pregnancy termination for prenatally diagnosed Klinefelter syndrome and other sex chromosome polysomies. Am J Med Genet 1998;80:330-334.
  • Moore LL, Bradlee ML, Singer MR, Rothman KJ, Milunsky A. Chromosomal anomalies among the offspring of women with gestational diabetes. Am J Epidemiol. 2002;155:719-724.
  • Nielsen J, Videbech P. Diagnosing of chromosome abnormalities in Denmark. Clin Genet 1984;26:422-428.
  • 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;87:81-83.
  • Perrotin F, Guichet A, Marret H, Potin J, Body G, Lansac J. Devenir prenatal des anomalies des chromosomes sexuels diagnostiquees pendant la grossesse. Analyse reptrospective de 47 cas. J Gynecol Obstet Biol Reprod (Paris) 2000;29:668-676.
  • Pettenati M, Wheeler M, Bartlett DJ, Subrt I, Rao N, Kroovand RL, Burton BK, Kahler S, Park HK, Cosper P, Kelly DR, Ranells JD. 45,X/47,XYY Mosaicism: clinical discrepancy between prenatally and postnatally diagnosed cases. Amercian Journal of Medical Genetics, 39:42-47, 1991.
  • Robinson DO, Jacobs PA. The origin of the extra Y chromosome in males with a 47,XYY karyotype. Human Molecular Genetics, Vol. 8, No. 12, 1999.
  • Ryall RG, Callen D, Cocciolone R, Duvnjak A, Esca R, Frantzis N, Gjerde EM, Haan EA, Hocking T, Sutherland G, Thomas DW, Webb F. Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening. Prenat Diagn 2001;21:553-557.
  • Sagi M, Meiner V, Reshef N, Dagan J, Zlotogora J. Prenatal diagnosis of sex chromosome aneuploidy: possible reasons for high rates of pregnancy termination. Prenat Diagn 2001;21:461-465.
  • Sanger R, Tippett P, Gavin J, Teesdale P, Daniels GL. Xg groups and sex chromosome abnormalities in people of northern European ancestry: an addendum. J Med Genet 1977;14:210-13.
  • Schwartz ID, Root AW. The Klinefelter syndrome of testicular dysgenesis. Endocrinol Metab Clin North Am 1991;20:153-163.
  • Sebire NJ, Snijders RJ, Brown R, Southall T, Nicolaides KH. Detection of sex chromosome abnormalities by nuchal translucency screening at 10-14 weeks. Prenat Diagn 1998;18:581-584.
  • Shaw GM, Carmichael SL, Nelson V. Congenital malformations in offspring of Vietnamese women in California, 1985-97. Teratology 2002a;65:121-124.
  • Spencer K, Tul N, Nicolaides KH.. Maternal serum free beta-hCG and PAPP-A in fetal sex chromosome defects in the first trimester. Prenat Diagn 2000;20:390-394.
  • Verp MS, Bombard AT, Simpson JL, Elias S. Parental decision following prenatal diagnosis of fetal chromosome abnormality. Am J Med Genet 1988;29:613-622.
  • Videbech P, Nielsen J. Chromosome abnormalities and season of birth. Hum Genet 1984;65:221-231.

 

 
Please Note: The primary purpose of this report is to provide background necessary for conducting cluster investigations. It summarizes literature about risk factors associated with this defect. The strengths and limitations of each reference were not critically examined prior to inclusion in this report. Consumers and professionals using this information are advised to consult the references given for more in-depth information. 

This report is for information purposes only and is not intended to diagnose, cure, mitigate, treat, or prevent disease or other conditions and is not intended to provide a determination or assessment of the state of health. Individuals affected by this condition should consult their physician and when appropriate, seek genetic counseling.

For more information:

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Document E58-10957B                    Revised November 2005

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Last updated February 10, 2012