Polyhydramnios, fetal overgrowth, and macrocephaly: Prenatal ultrasound findings of Costello syndrome

Abstract

Costello syndrome is a multiple congenital anomaly syndrome consisting of dysmorphic facies, cutis laxa, short stature, developmental delay, and mental retardation. Complications include failure to thrive, hypertrophic cardiomyopathy with arrhythmias, and benign and malignant tumors. This report describes a new case of Costello syndrome in a preterm infant born at 27 weeks gestation and diagnosed with Costello syndrome at 7 weeks of life who died at 6 months of age due to cardiac and pulmonary complications. In addition, data were compiled from parent surveys including growth parameters on 16 infants who were subsequently diagnosed with Costello syndrome and had mutation confirmation. The most common prenatal findings in the literature and in this cohort were polyhydramnios and fetal overgrowth with relative macrocephaly. Based on this study, ultrasound identification of polyhydramnios in the context of prenatal overgrowth, especially with relative macrocephaly, needs to raise the possibility of a diagnosis of Costello syndrome in the fetus because of the life-threatening cardiac complications that may occur early in the newborn period.

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

“…Prenatal onset of HCM has not yet been observed in Costello syndrome Smith et al, 2009], even in a 31-week fetus scanned using 3-D ultrasonography who had ''cardiac hypertrophy'' postnatally [Kuniba et al, 2009].…”

“…The literature tends to be biased towards the severe forms of Costello syndrome, such as the fetal phenotype [Kuniba et al, 2009;Lin et al, 2009;Smith et al, 2009] and lethal infantile presentation [Hinek et al, 2005;Digilio et al, 2007;Limongelli et al, 2008;Lo et al, 2008], thus, our study patients expand the phenotypic spectrum to the mild end. It is reasonable to assume that diagnosis of Costello syndrome is more likely to be missed in early lethal cases when infants with hypertrophic cardiomyopathy and hypotonia may be diagnosed as having a metabolic or mitochondrial disease.…”

Signaling to Cardiac Hypertrophy: Insights from Human and Mouse RASopathies

“…The age at which HCM is diagnosed ranges from infancy, in patients with a severe form of the rare neonatal phenotype, to childhood, the more common age of presentation (10). In studies focused on fetuses, investigators failed to diagnose prenatal onset of HCM, at least in CS (24,25). So far, hypertrophy has seemed to develop as a counteraction of the cardiomyocyte to increased hemodynamic demands.…”

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings

“…Costello syndrome is associated with polyhydramnios, fetal overgrowth, a relative macrocephaly and to a lesser extent with nuchal thickening, hydrops, ventriculomegaly, pyelectasia and fetal atrial tachycardia/arrhythmia. [17][18][19] Prenatal features of NS are increased nuchal translucency (NT), distended jugular lymphatic sacs (JLS), cystic hygroma, hydrops fetalis, pleural effusion, polyhydramnios, CHD and renal abnormalities. [20][21][22][23][24] The first prenatal DNA diagnosis of NS in a fetus with massive cystic hygroma, pleural effusion and ascites showed a mutation in the PTPN11 gene.…”