Other causes include presence of a robertsonian translocation in combination with two free copies of chromosome 21. Often in such cases, one parent is a balanced carrier of the robertsonian translocation. Recurrence risk of trisomy 21 depends on the specific robertsonian translocation and the sex of the carrier parent. Prenatal diagnosis (chromosome analysis) should be offered to all robertsonian translocation carriers.
Relative Tests and Diagnostic Value
Prenatal maternal screening: Risk of trisomy 21 may be calculated with first-trimester, second-trimester, or both semester (integrated/sequential) screening modalities that include measurement of maternal serum analytes and fetal ultrasound. Detection rates vary depending on the screening modality and on the false-positive rate. The second-semester maternal quad screen can detect 80% of affected pregnancies with a 5% false-positive rate; integrated testing can detect 90% with a 5% false-positive rate.
Chromosome analysis: Diagnostic for trisomy 21 and can be performed on chorionic villus, amniotic fluid, and peripheral blood.
FISH: Interphase FISH may be performed for rapid enumeration on chorionic villus, amniotic fluid, and peripheral blood.
Non-invasive prenatal testing (NIPT) is available.
TURNER SYNDROME (45,X KARYOTYPE AND VARIANTS)
Definition
Turner syndrome is widely known as 45,X, although approximately 50% of individuals with Turner syndrome have a variation of this karyotype. About 15% of patients carry one normal X chromosome and one structurally aberrant X chromosome. Approximately 25–30% of patients are mosaic with one 45,X cell line and a second cell line that might contain, among others, two normal X chromosomes (i.e., 45,X/46,XX), one normal and one abnormal X chromosome (i.e., 45,X/46,X,i(Xq)), or one X and one Y chromosome (i.e., 45,X/46,XY).
Who Should Be Suspected?
A number of phenotypic abnormalities are pathognomonic for Turner syndrome. The most characteristic findings are short stature (under 5 ft or 150 cm) and gonadal dysgenesis (usually streak gonads). Fetal cystic hygroma is common, resulting from lymphedema and leading to postnatal neck webbing. Other associated anomalies include low posterior hairline, shield chest with widely spaced nipples, cubitus valgus, cardiac anomalies (frequently coarctation of the aorta), and renal anomalies.
Relevant Tests and Diagnostic Value
Obtaining the karyotype of patients with Turner syndrome is clinically important. Although many of the individual symptoms of Turner syndrome seem to be randomly distributed with respect to different deletions throughout the X chromosome, some correlations with phenotype can be made. Most individuals with breakpoints distal to Xq25 have few abnormalities except occasional secondary amenorrhea or premature menopause. Short stature is almost always associated with deletions of the distal portion of the short arm; it is seen less often with long arm deletions.
Determination of the presence of Y chromosomal material is of critical medical importance because its presence leads to an increased risk for gonadoblastoma in sex-reversed individuals. As such, molecular studies for detection of Y chromosomal DNA should be performed. In addition, rare patients with features of Turner syndrome are determined to have a 46,XY karyotype missing a portion of the Y chromosome. These individuals also have an increased risk of gonadoblastoma.
