Most common chromosomal abnormality that occurs in females. Only 1%of conceptuses with Turner syndrome survive to term.
Incidence is 1 in 2500 female livebirths. No association with advanced maternal age.
Approximately 50% of cases have full 45, X, 30% to 40% have mosaicism, and 10% to 20% have a structural abnormality of one X chromosome. Severity of clinical phenotype cannot be predicted from the karyotype.
Characteristic sonographic abnormalities include very large cystic hygroma, hydrops fetalis, short femur, coarctation of the aorta, hypoplastic left heart, and renal anomalies.
In the presence of lymphatic or cardiac malformations, delivery should occur at a tertiary center.
Major considerations for long-term follow-up include: growth hormone treatment for short stature, estrogen treatment for feminization and bone health, monitoring for cardiovascular complications such as aortic dilatation and rupture, severe hypertension, and propensity toward autoimmune disease.
Intelligence is normal, but there may be mild learning difficulties related to visual-spatial issues.
Phenotype may differ depending upon whether the maternal or paternal X is retained. In ~75% of women the maternal X remains.
Turner syndrome is named for Henry Turner, who in 1938 recognized the combination of sexual infantilism, webbed neck, and cubitus valgus to be a distinct entity. However, the underlying chromosomal abnormality in the condition was not recognized until 1959 (Ford et al., 1959). Turner syndrome exclusively affects females, and affected patients are generally missing all or part of the X chromosome in all or part of their cells. Postnatally, Turner syndrome is clinically suspected because of short stature, gonadal dysgenesis, or lymphedema. There are no pathognomonic clinical features (Hall and Gilchrist, 1990).
Turner syndrome is the most common chromosomal abnormality that occurs in females. It affects an estimated 3% of all females conceived, but only 1% of these survive to complete a full-term gestation. There are between 50,000 and 75,000 girls and women with Turner syndrome in the United States (Saenger, 1996).
The prevalence of Turner syndrome in Denmark is 392 in 100,000 cases ascertained at chorionic villus sampling (CVS), 176 in 100,000 amniocentesis cases, and 32 in 100,000 live female births (Højberg-Gravholt et al., 1996). The incidence of Turner syndrome of 1 in 2500 female livebirths is the most commonly quoted figure (Hall et al., 1982). Turner syndrome does not increase in incidence with advanced maternal age (Koeberl et al., 1995).
Turner syndrome is highly lethal in embryonic and fetal life. Although 1% to 2% of all conceptuses have 45, X, 98% to 99% of affected fetuses miscarry. When spontaneous abortuses are karyotyped, approximately 10% of them are shown to have Turner syndrome (Hall et al., 1982).
Of patients diagnosed with Turner syndrome, approximately 50% have 45, X (monosomy X) (Figure 134-1). An additional 30 to 40% of patients have mosaicism with a normal cell line. However, it is postulated that the incidence of mosaicism is in reality much higher, and that cases that survive to a full-term delivery have placental mosaicism. Of The remaining cases of Turner syndrome, 10% to 20% have a structural rearrangement of the X chromosome, most commonly, isochromosome X (duplication of one arm of the X chromosome with loss of the other arm). Any combination of physical features can be seen with any X chromosomal abnormality. The severity of the clinical phenotype cannot be predicted from the karyotype (Hall et al., 1982).
Sonography is the most useful tool to detect cases at risk for Turner syndrome. The prenatal sonographic findings that are characteristically found in Turner syndrome include increased nuchal translucency measurement (Kagan et al., 2006), cystic hygroma, renal malformations, and left-sided cardiac anomalies (Papp et al., 2006).
Bronshtein et al. (2003) described a “classic” cluster of abnormalities visualized by transvaginal sonography in 13 fetuses with Turner syndrome studied at 14 to 16 weeks. These included very large cystic hygroma, severe subcutaneous edema, hydrops fetalis, short femur, and narrow aortic arch. Cystic hygromas are the fetal expression of anomalous lymphatic development (see Chapter 31). The most common anatomic site for cystic hygromas is the nuchal region (Figure 134-2). Cystic hygroma is an ominous prenatal finding. In one study, 93% of continuing pregnancies with cystic hygroma resulted in fetal or neonatal death (Cohen et al., 1989). However, several cases have documented resolution of the cystic hygroma in Turner syndrome. For example, Brookhyser et al. (1993) described the spontaneous resolution of a nuchal cystic hygroma and pleural effusion during the third trimester in a fetus with Turner syndrome. There was a good outcome for this case. Similarly, Chodirker et al. (1988) also described resolution of a cystic hygroma, but demonstrated the postnatal appearance of a webbed neck (pterygium colli) and a rotated ear. Other manifestations of lymphatic malformations include transient bilateral pleural effusion, which has been demonstrated as early as the first trimester using transvaginal imaging (Shimizu et al., 1997).
The sonographic diagnosis of cystic hygroma is made by the demonstration of a thin-walled multiseptated asymmetrical fluid-filled mass attached to the lateral aspect of the fetal head or neck (see Figure 134-2). The mass is in a constant location with respect to the fetal occiput and is independent of fetal motion (Garden et al., 1986; Donnenfeld and Mennuti, 1988).
A somewhat rarer presentation of the fetal lymphatic malformations seen in Turner syndrome is isolated fetal ascites. Wax et al. (1992) presented a case of massive fetal ascites and polyhydramnios detected at 32 weeks of gestation resulting from congenital intestinal lymphangiectasia. The diagnosis was later shown to be Turner syndrome.
Other manifestations of Turner syndrome include cardiovascular anomalies. In 2003, Surerus et al. reported on 53 fetuses with 45, X; 47 of them were ascertained by the presence of an increased nuchal translucency measurement. Cardiac malformations were detected in 33/53 fetuses (62.2%). Nuchal translucency measurement was greater in the fetuses with congenital heart disease than in those without. Coarctation of the aorta was observed in 24/53 fetuses (45.3%). Hypoplastic left heart syndrome was the next most common finding (seen in 7/53, or 13.2% of cases). These authors concluded that structural heart disease is more common in prenatal than postnatal life, and that the type of lesions observed was different. For example, postnatally, bicuspid aortic valve is the most common abnormality in Turner syndrome (Gøtzsche et al., 1994).
Approximately 30% to 60% of patients with Turner syndrome have a structural or positional renal anomaly (Hall et al., 1982; Hall and Gilchrist, 1990). Horseshoe kidney is especially common, seen in 20% of patients with Turner syndrome. Other typical malformations include duplication of the collecting system (20% of cases) and malrotation (seen in 50% of kidneys). Renal anomalies seen in Turner syndrome rarely result in renal malfunction but may predispose to postnatal urinary tract infections.
The differential diagnosis varies according to the age at presentation of symptoms. Prenatally, the lymphatic malformations predominate. The differential diagnosis for cystic hygroma includes cystic teratoma, meningocele, encephalocele, and neural tube defect (Bluth et al., 1984). Cystic hygroma can be differentiated from neural tube defects by the demonstration of bilateral echo-free spaces divided by septae. In addition, with a cystic hygroma there is an intact cranial vault and an intact spinal canal. Ascites and an edematous placenta can be seen in association with cystic hygroma, but is generally not seen in association with neural tube defects or cystic teratoma.
At birth, peripheral lymphedema has the differential diagnosis of Milroy disease, and other single-gene disorders associated with lymphedema, such as lymphedema with recurrent cholestasis or lymphedema with intestinal lymphangiectasia.
Turner syndrome can be detected later in life because of short stature or amenorrhea. The differential diagnosis of short stature includes familial short stature, Noonan syndrome, dyschondrosteosis (Leri–Weill syndrome), growth hormone deficiency, and hypothyroidism (Hall et al., 1982).
Noonan syndrome can be distinguished from Turner syndrome on the basis of a normal chromosome analysis.
ANTENATAL NATURAL HISTORY
Turner syndrome results from haploinsufficiency for specific genes located on the X chromosome. It is highly lethal in utero (Committee on Genetics, American Academy of Pediatrics, 1995) (Figure 134-3). It is estimated that as many as 80% of liveborn infants with Turner syndrome have an additional normal cell line that permits postnatal survival (Amiel et al., 1996). In one study of four fetuses with Turner syndrome, three were phenotypically normal and one had malformations. All three that were phenotypically normal had the presence of an additional normal cell line. In the one fetus with malformations, no normal cell line could be demonstrated in any of the tissues examined (Amiel et al., 1996). In a study of 16 first trimester fetuses with a variety of chromosomal abnormalities, a monoclonal antibody was used to study the distribution syndrome of lymphatic vessels (von Kaisenberg et al., 1999). In the 3 fetuses with Turner syndrome, the vessels were hypoplastic in the upper dermis.
It is thought that the lymphatic malformations originate from hypoalbuminemia. In a study by Shepard and Fantel (1986), fetuses with Turner syndrome had lower albumin levels in their plasma as compared with control fetuses. These investigators postulated that early edema resulting from hypoalbuminemia may interfere with the normal development of the lymphatics. In fact, most of the congenital anomalies seen in Turner syndrome can be explained on the basis of lymphedema at critical points in development (Hall and Gilchrist, 1990). Some investigators hypothesize that the lymphedema is the result offailure to open embryonic lymph channels. Pterygium colli (webbed neck) results from an in utero persistence of embryonic lymph sacs.
A correlation between neck webbing and the presence of coarctation of the aorta has been noted by Clark (1984), who postulated that large lymph channels adjacent to the aortic outflow tract misdirect blood flow to the aorta, thus producing an abnormal blood flow through the ductus arteriosus. In a study of 12 fetuses terminated between 16 and 26 weeks of gestation because of a prenatal finding of cystic hygroma or hydrops, 8 demonstrated a consistent constellation of cardiac defects. These included a small ascending aorta, relatively large pulmonary arteries that were 1.5 to 3 times the size of the aorta, a large patent ductus arteriosus, and a juxtaductal coarctation of the aorta (Lacro et al., 1988). The high incidence of left-sided flow defects among the fetuses in this study supports the hypothesis that there is a pathogenetic relationship between lymphatic obstruction and the subsequent development of congenital heart disease. In this study, lymphatic distention was demonstrated on histologic sections obtained through the base of the heart and the pulmonary hila. These data support the concept that hydrostatic pressure occurring within the jugular lymphatic sac can also distend the cardiac lymphatics (Lacro et al., 1988).