A Pediatric Patient With Noonan Syndrome and Late Onset Unilateral Lymphedema

Abstract

Abstract Introduction: Noonan syndrome is a common autosomal dominant disorder with a prevalence of 1 in 1000-2500 births. The lymphatic disorders in Noonan syndrome are rare and usually bilateral. We present a 14-year-old male with Noonan syndrome and late-onset unilateral lower extremity lymphedema. Case presentation: A 14-year-old male with Noonan syndrome due to a pathogenic mutation in the RIT1 gene (c.265T>C p.Tyro89His) presented to emergency room due to progressive swelling of the right lower extremity. No history of recent trauma or injury. He had a history of small mid-muscular ventricular septal defect (VSD), chylothorax with right-sided pleural effusions during infancy, sensorineural hearing loss with bilateral hearing aids, and undescended testes status post-surgery. He had been on growth hormone (GH) therapy since age 12 years with good adherence and no reported side effects. In the emergency room, initial laboratory evaluation and Doppler ultrasound ruled out deep venous thrombosis. Physical exam was remarkable for edema of the right lower extremity, warm to touch, with erythema, not painful. Due to initial concerns for cellulitis, the patient was treated with antibiotics. Erythema improved but not the edema. Cardiac evaluation including echocardiogram with stable, unchanged VSD was unremarkable. Patient underwent additional workup notable for an albumin level of 4.4g/dl (3.4-5.0), Immunoglobulin (Ig) A 53 mg/dl (66-436), IgG 788 mg/dl (791-1643), IgM 82 mg/dl (43-279) and a stool alpha antitrypsin level of 0.65 mg/g (0.0-0.5) ruling out protein-losing enteropathy (PLE). Growth hormone was held initially and restarted after 2 months due to clinical improvement, but just for one week due to worsening swelling. Lymphoscintigraphy of lower extremities showed an asymmetry between the right and left leg in the transit, suggesting a mild lymphatic abnormality in the right leg. There was a significant improvement in terms of his lymphedema with physical therapy and compressive stocking after 6 months. He has been off growth hormone therapy since then. Discussion: Patients with Noonan syndrome may develop lymphedema and PLE, although findings are usually bilateral. Interestingly our patient has unilateral lymphedema that has been improving with compression stocks and physical therapy. Our patient was on GH therapy for 2 years before he developed lymphedema and although growth hormone causes water retention, we would not expect a selective involvement as in our patient. Based on his history of chylothorax we decided to perform a Lymphoscintigraphy that confirmed an abnormality in the lymphatic system of the right lower extremity. The effect of GH once restarting pointed it was a precipitating factor instead of the cause. Late-onset lymphedema is an uncommon presentation but should be a diagnosis that we have to keep in mind when patients with Noonan syndrome are presenting with edema.