LYMPHATIC SYSTEM MALFORMATIONS IN NOONAN SYNDROME: TWO CASE REPORTS AND IMAGING ANALYSIS

Abstract

L ymphedema is a well-known complication of Noonan syndrome (NS) but the lymphatic malformations in NS are poorly understood. We report clinical, genetic, and imaging information about a boy and girl with NS and late-onset lower extremity lymphedema. A de novo missense mutation of RIT1 (NM_006912.5) c.246T>A, p.Phe82Leu was identified in the girl, who also showed systemic lymphatic hyperplasia and dysfunction. Magnetic resonance lymphangiography (MRL) of the boy clearly demonstrated segmental dilated and hyperplastic lymphatics with impaired transport function in an affected limb and pelvic region. Indocyanine green lymphography (ICGL) showed delayed and partial enhancement of the lymph vessels in the affected limb but no lymph reflux was detected. No causative mutation was identified in the second case. Lymphoscintigraphy (LSG) failed to show lymph vessels in either of the children. Our study showed that MRL is a reliable and accurate test that can be used to demonstrate morpho-logical and functional defects of the lymphatic system. Moreover, ICGL is sufficiently sensitive to determine the functional condition of peripheral lymph vessels. The combined use of imaging modalities can give an accurate diagnosis of complex lymphatic system anomalies in NS and other syndromic diseases.