P38.09: Prenatal sonographic findings in a case of cardio‐facio‐cutaneous syndrome

Abstract

The differential diagnosis of the karyotypically normal fetus with cystic hygromas is extensive, and includes several syndromes for which DNA diagnosis can now be done. We present a case in which cystic hygromas had been seen at 17 weeks. Karyotyping was normal. On our initial sonogram, at 21 weeks, findings included cystic hygroma, anteriorly displaced aorta, prominent superior vena cava, and globular appearance to the left ventricle. Polyhydramnios and a protruberant fetal tongue developed in the third trimester. Delivery was prompted by cessation of fetal movement at 32 weeks gestation. Cord blood gas studies were normal. The infant had dysmorphic features and hypotonia and developed progressive cardiomyopathy with pulmonic stenosis and concentric biventricular hypertrophy. Differential diagnosis included Noonan, Costello, and CFC syndromes. The neonate subsequently expired. When DNA testing for CFC became available, a stored specimen was checked, and demonstrated a heterozygous missense mutation (c.1931 G > T) in exon 11) of the BRAF gene consistent with the diagnosis of CFC syndrome. Cardio-facio-cutaneous (CFC) syndrome is a rare, devastating, sporadic syndrome which has recently been linked to gain-of-function mutations in the BRAF, KRAS, MEK1 and MEK2 genes of the RAS-extracellular signal-regulated kinase pathway. Abnormalities include developmental delay, postnatal growth impairment, characteristic facial features (prominent forehead, temporal narrowing, hypotelorism, posteriorly rotated ears) with or without web neck, cutaneous manifestations (sparse brittle hair, absent eyebrows, and hyperkeratosis of the palms and soles), and a variety of cardiac anomalies, including pulmonic stenosis and hypertrophic cardiomyopathy, often manifest only after birth. In utero diagnosis has not been described. Whether the unique cardiac findings described here will be seen in other cases awaits further sonographic observations. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.