The overgrowth syndromes refer to a heterogeneous group of conditions characterized by generalized excessive growth for gestational age. Many overgrowth syndromes are associated with anomalies, developmental delay, and a propensity for tumor development. Diagnostic characterization has been difficult because of the overlapping clinical features in many of these syndromes (Cytrynbaum et al., 2005). Recent studies using high-resolution cytogenetic techniques, as well as molecular analysis of several genes, have illustrated the fact that there is substantial clinical as well as molecular overlap amongst the overgrowth disorders (Baujat et al., 2005).

The overall incidence of fetal overgrowth is unknown but it is not rare. The incidence of Beckwith–Wiedemann syndrome is about 1 in 13,700 livebirths (Cytrynbaum et al., 2005). Beckwith–Wiedemann syndrome is more common in women who have undergone in vitro fertilization to conceive. It is estimated that Beckwith–Wiedemann syndrome occurs in 1 in 4000 deliveries to women who have used assisted reproductive technology. Another common condition associated with fetal overgrowth is Sotos syndrome, which has an incidence of 1 of 15,000 livebirths (Tatton-Brown and Rahman, 2007). The incidence of some of the other rare genetic conditions, suchas Simpson-Golabi-Behmelsyndrome (SGBS), is unknown.

In the obstetric literature, there has been no prospective study performed to ascertain the outcome of fetuses documented to have overgrowth. There have, however, been reports of prenatal ultrasound findings in fetuses that were postnatally diagnosed as having a specific syndrome. For example, Reish et al. (2002) described three unrelated cases of Beckwith–Wiedemann syndrome and tabulated anomalies that were detected prenatally. The anomalies common to all of the fetuses included overgrowth, polyhydramnios, placentomegaly, macroglossia, and a distended abdomen. In addition, Le Caignec et al., (2004) described a case of Beckwith–Wiedemann syndrome in a 28-year-old G3P1-pregnant woman who underwent sonography at 28 weeks of gestation. The fetus was macrosomic, but also had bilateral enlarged echogenic kidneys with a loss of corticomedullary differentiation.

An increasingly appreciated cause of fetal overgrowth is Sotos syndrome. There has been one prenatal description of the findings of Sotos syndrome (Chen et al., 2002). This group described fetal findings at 31 weeks of gestation, which included macrocephaly, an abnormally shaped skull, polyhydramnios, and right hydronephrosis. A subsequent scan at 33 weeks demonstrated the presence of fetal overgrowth. Postnatally, this fetus underwent magnetic resonance imaging (MRI), which showed enlargement of the lateral ventricles, hypoplasia of the corpus callosum, a mega cisterna magna, and a persistent cavum septum pellucidum.

The prenatal sonographic findings in pregnancies affected with SGBS were summarized in Hughes-Benzie et al. (1994). These authors described a case of SGBS in which sonography was performed for an increased maternal serum alpha-fetoprotein measurement. The fetal findings included macrosomia, polyhydramnios, omphalocele, and enlarged or cystic kidneys. Cardiac anomalies are also common in SGBS (Lin et al., 1999), but there have been no prenatal reports of their detection in this condition.

The differential diagnosis for fetal overgrowth is shown in Table 124-1. The differential diagnosis is complicated by the fact that many of these conditions have substantial clinical overlap. The most common reason for fetal “overgrowth” is incorrect gestational dating. Once this has been ruled out, the second most common cause is hyperinsulinism due to maternal diabetes. Sustained maternal hyperglycemia results in beta cell hyperplasia and fetal hyperinsulinism, which in turn induces fetal macrosomia with a weight that is greater than length.

There are multiple syndromic causes of fetal overgrowth. Sotos syndrome, also known as cerebral gigantism, consists of macrosomia, macrocephaly, a typical postnatal facial appearance, mild developmental delay, and advanced dental maturation. Weaver syndrome is now considered to be allelic with Sotos syndrome. Patients with Weaver syndrome have prenatal overgrowth, advanced skeletal maturation, advanced bone age, a distinctive postnatal facial appearance that consists of micrognathia with a deep horizontal chin crease, deep set nails. Approximately 80% of patients with Weaver syndrome have developmental delay.

Beckwith–Weidemann syndrome is in the differential diagnosis for fetal overgrowth. Affected fetuses have macrosomia, macroglossia (Figures 124-1 and 124-2) (see Chapter 27), and sometimes, an abdominal wall defect. Patients who have Beckwith–Wiedemann syndrome have visceromegaly and ear anomalies (Figure 124-3) that are only detectable postnatally.