Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing

Abstract

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

Keywords: Noonan syndrome; chylothorax; genomic DNA sequence; lymphatic dysplasia; pulmonary lymphangiectasis.

Figure 1.

Composite photograph with gross and photomicrographs from the autopsy. A. The lungs after 24 h of formalin fixation. When fresh, they were pale pink with a slightly bumpy pleural surface. The aorta is horizontally placed at the upper portion of the photograph. B. Hematoxylin-and eosin (H&E)-stained photograph taken from the lung with the 4× -lens depicts the pleural surface and part of the pulmonary parenchyma. Notice the dilated vessels. C. Same field of view and magnification as in 1-B, but stained by immunohistochemistry for D2-40 highlights the lymphatic origin of dilated vessels. D. The upper part of the abdominal organs demonstrates the liver with gallbladder, intestine and congested mesenteric vessels. E. The H&E-stained photomicrograph from intestine and mesentery with the 4× -lens shows the intestine in the right lower corner and numerous dilated mesenteric vessels. F. Same field of view and magnification as in 1-E, but stained by immunohistochemistry for D2-40 highlights the lymphatic nature of dilated vessels.