**2. Sex chromosome disorders of sex development**

Although the majority of sex chromosome abnormalities do not have genital differences as a clinical finding, some do. At conception 2% of all pregnancies are Turner syndrome and is one of the most common chromosome abnormality associated with first trimester miscarriages. The condition is highly lethal in-utero and thus the incidence at birth is 1:2500 female newborn. In almost 2/3 of cases, i.e. 60%, the karyotype is 45,X while in 15%, the condition is associated with mosaicism, i.e. 45, X/47,XXX, 45,X/46, XX/47,XXX, 45,X/46, XY, and 45,X/46, XX. Other chromosome abnormalities associated with Turner syndrome include structural abnormalities involving the X chromosome, e.g., 46,X,r(X), 46,X,Xp-, and

**65**

treatment [12].

*Approach to the Newborn with Disorders of Sex Development*

46,X,i(Xq) in 10% of cases, structural abnormality of the X chromosome in mosaic state in 10% of cases, with 5% in the other [8]. The condition can be detected prenatally, due to abnormalities in the lymphatic system, with the fetus presenting with heart lesions, specifically left-sided, hydrops fetalis, increased nuchal translucency or cystic hygroma. Postnatally, female babies can present with typical facial features, including epicanthic folds, droopy eyelids, down slanting palpebral fissures, micrognathia, and low set and prominent ears. The neck is often webbed and short with a nuchal hairline that is low, as well as swelling (lymphedema) of the feet and hands, and deep set nails. Left-sided cardiac anomalies are seen in 50% of the cases (hypoplastic left heart, coarctation of the aorta, bicuspid aortic valve, and aortic stenosis) with an increased risk for aortic dissection during pregnancy and the puerperal period if they decide to conceive using a donor egg. It is also associated with horseshoe kidneys as well as short stature, streak gonads and thus lack of

Genetic analysis for Y chromosome material, including in a mosaic state can be picked up by chromosome microarray analysis and is important since girls with mosaicism for 46, XY [45,X/46,XY] have an increased risk for gonadoblastoma and dysgerminoma and may have absent uterus. A large British series in the literature, looking at women with Turner syndrome, showed an increased incidence not only of gonadoblastoma, but also uterine cancer, as well as possibly pediatric brain cancers. This study also demonstrated a lower incidence of breast cancer [9–11]. The incidence of Klinefelter syndrome, i.e. 47, XXY is approximately 1 in 500 males. Clinically, they can present with testes on the smaller end of the spectrum, which can impact production of testosterone and normal sperm. Otherwise, they do not have genital differences. They have normal appearing facies but can be taller in height than average and about 50% develop gynecomastia at puberty. Boys with Klinefelter syndrome can present with neurodevelopmental/neurobehavioral issues; however encouraging results, for behavioral as well as for the physical features described above, have been seen with early administration of testosterone. The optimal timing and dosage of hormonal therapy has not been established and further studies and long term follow-up are needed prior to this becoming standard

Mosaicism for 45,X/46, XY, also previously called mixed gonadal dysgenesis, is a rare condition with an approximate incidence reported in Denmark of less than 1/15,000 live births [8]. It has been suggested that transformation of the indifferent gonad to testes [13–15] is due to the existence of Y chromosome in the gonadal ridge. The spectrum of genital differences with this karyotype is varied, ranging from females presenting with Turner syndrome, to males with ambiguous genitalia, to phenotypically normal males. Gonadal function in most 45,X/46, XY males, even those with genital ambiguity, seems sufficient for spontaneous puberty and patients

appear to benefit from GH treatment when needed [16].

**3. 46, XY disorders of sex development**

2.Disorders of androgen synthesis

46, XY DSD can be divided into categories;

1.Disorders of testicular (gonadal) development

Both categories lead to feminization or abnormal genitalia.

spontaneous puberty. However, they can conceive using a donor egg.

*DOI: http://dx.doi.org/10.5772/intechopen.94570*

#### *Approach to the Newborn with Disorders of Sex Development DOI: http://dx.doi.org/10.5772/intechopen.94570*

*Congenital Anomalies in Newborn Infants - Clinical and Etiopathological Perspectives*

2.Oogenesis starts and ends prior to 20 weeks gestation while spermatogenesis

*Diagram of the known major genes involved in testicular and ovarian differentiation and function* 

3.The ovarian hormonal production/function is linked to the process of follicle development and/or maintenance. The testes on the other hand can continue

The management of a newborn with abnormal genitalia has to be individualized taking into account the specific genital abnormalities as well as the parental and family as a whole. The decision regarding the sex of rearing should take into account the, surgical and non-surgical treatment, future pubertal development and fertility. This should be considered an urgent clinical situation and requires immediate assessment and counselling, and if possible, involvement of the DSD multidisciplinary core team including endocrinology, clinical genetics, genetic counselling, urology, obstetrics and gynecology, social work and psychology/

Although the majority of sex chromosome abnormalities do not have genital differences as a clinical finding, some do. At conception 2% of all pregnancies are Turner syndrome and is one of the most common chromosome abnormality associated with first trimester miscarriages. The condition is highly lethal in-utero and thus the incidence at birth is 1:2500 female newborn. In almost 2/3 of cases, i.e. 60%, the karyotype is 45,X while in 15%, the condition is associated with mosaicism, i.e. 45, X/47,XXX, 45,X/46, XX/47,XXX, 45,X/46, XY, and 45,X/46, XX. Other chromosome abnormalities associated with Turner syndrome include structural abnormalities involving the X chromosome, e.g., 46,X,r(X), 46,X,Xp-, and

producing testosterone even in the lack of spermatogenesis.

**2. Sex chromosome disorders of sex development**

starts only at puberty

**Figure 4.**

*(adapted from [3, 4]).*

psychiatry among others.

**64**

46,X,i(Xq) in 10% of cases, structural abnormality of the X chromosome in mosaic state in 10% of cases, with 5% in the other [8]. The condition can be detected prenatally, due to abnormalities in the lymphatic system, with the fetus presenting with heart lesions, specifically left-sided, hydrops fetalis, increased nuchal translucency or cystic hygroma. Postnatally, female babies can present with typical facial features, including epicanthic folds, droopy eyelids, down slanting palpebral fissures, micrognathia, and low set and prominent ears. The neck is often webbed and short with a nuchal hairline that is low, as well as swelling (lymphedema) of the feet and hands, and deep set nails. Left-sided cardiac anomalies are seen in 50% of the cases (hypoplastic left heart, coarctation of the aorta, bicuspid aortic valve, and aortic stenosis) with an increased risk for aortic dissection during pregnancy and the puerperal period if they decide to conceive using a donor egg. It is also associated with horseshoe kidneys as well as short stature, streak gonads and thus lack of spontaneous puberty. However, they can conceive using a donor egg.

Genetic analysis for Y chromosome material, including in a mosaic state can be picked up by chromosome microarray analysis and is important since girls with mosaicism for 46, XY [45,X/46,XY] have an increased risk for gonadoblastoma and dysgerminoma and may have absent uterus. A large British series in the literature, looking at women with Turner syndrome, showed an increased incidence not only of gonadoblastoma, but also uterine cancer, as well as possibly pediatric brain cancers. This study also demonstrated a lower incidence of breast cancer [9–11].

The incidence of Klinefelter syndrome, i.e. 47, XXY is approximately 1 in 500 males. Clinically, they can present with testes on the smaller end of the spectrum, which can impact production of testosterone and normal sperm. Otherwise, they do not have genital differences. They have normal appearing facies but can be taller in height than average and about 50% develop gynecomastia at puberty. Boys with Klinefelter syndrome can present with neurodevelopmental/neurobehavioral issues; however encouraging results, for behavioral as well as for the physical features described above, have been seen with early administration of testosterone. The optimal timing and dosage of hormonal therapy has not been established and further studies and long term follow-up are needed prior to this becoming standard treatment [12].

Mosaicism for 45,X/46, XY, also previously called mixed gonadal dysgenesis, is a rare condition with an approximate incidence reported in Denmark of less than 1/15,000 live births [8]. It has been suggested that transformation of the indifferent gonad to testes [13–15] is due to the existence of Y chromosome in the gonadal ridge. The spectrum of genital differences with this karyotype is varied, ranging from females presenting with Turner syndrome, to males with ambiguous genitalia, to phenotypically normal males. Gonadal function in most 45,X/46, XY males, even those with genital ambiguity, seems sufficient for spontaneous puberty and patients appear to benefit from GH treatment when needed [16].
