Lymphatic dysplasia evaluated by indocyanine green lymphography in congenital myotonic dystrophy

Myotonic dystrophy (DM) is the most common type of muscular dystrophy in adults and is characterized by multiorgan involvement. Congenital DM (CDM), the most severe form of DM, is often associated with respiratory insufficiency and early death.1 Although hydrops and chylothorax have been reported in association with CDM, lymphatic vessel formation has yet to be evaluated in this condition.2, 3 We report here a case of CDM diagnosed with lymphatic dysplasia using indocyanine green (ICG) lymphography, presenting with marked generalized edema and pleural and peritoneal effusions. A 34-year-old mother with one previous delivery was suspected to have DM due to myopathic facies, myotonia, elevation of serum creatine kinase, and polyhydramnios. No fetal hydrops or pleural effusion was noted. Preterm labor began at 30 weeks of gestation, and an emergency cesarean section was performed due to umbilical cord prolapse. The male infant (birth weight: 1476 g) was intubated immediately after birth due to generalized hypotonia and apnea. Apgar scores at 1, 5, and 10 min were 1, 1, and 3. He had an inverted V-shaped upper lip and joint contracture of the extremities. Genetic testing revealed approximately 2100 CTG repeats in the myotonic dystrophy protein kinase gene, confirming CDM. Chest X-ray showed a bell-shaped thorax, suggestive of pulmonary hypoplasia. Echocardiography indicated pulmonary hypertension. Venous blood gas analysis showed respiratory acidosis, and NO inhalation therapy was administered with ventilatory management. Pneumothorax occurred on days 4 and 6, followed by pneumoperitoneum on day 11, requiring drainage. From day 16, generalized edema, pleural effusion, and ascites developed. Circulatory support included steroids, catecholamines, albumin, and fresh frozen plasma. An examination of pleural and peritoneal effusion revealed that the total leukocyte counts in both pleural and peritoneal effusions were 500/mm3, with lymphocytes accounting for 94% and 88% of the white blood cells in the pleural fluid and ascites, respectively. Despite low triglyceride levels and clear appearance of the fluids due to lack of enteral feeding, the effusions were considered lymphatic in origin. Suspecting lymphatic abnormalities, we performed ICG lymphography. ICG lymphography was performed as previously reported4 0.25 mg (0.1 mL) of ICG (Diagnogreen 0.25%; Daiichi-Sankyo, Tokyo, Japan) was injected subcutaneously into the first web space of the right foot. After injection, circumferential fluorescent images of the lymphatic drainage channels in the extremities and the trunk were obtained using an infrared camera system (Photodynamic Eye Neo; Hamamatsu Photonics K.K., Hamamatsu, Japan). ICG lymphography revealed that a normal linear pattern was scarcely observed, while diffuse dermal backflow was evident in the extremities and external genitalia, with reflux extending to the contralateral thigh (Figure 1). Leakage from the abdominal drain was also observed. Based on these findings, the patient was diagnosed with severe lymphatic dysplasia. The patient died of circulatory failure at 2 months of age. ICG lymphography has been used for the evaluation of lymphedema in adults. This method is also useful for assessing lymphatic dysplasia in neonates with congenital lymphatic pleural effusion and ascites.4 Findings of a diffuse dermal backflow pattern on ICG lymphography are thought to reflect severe lymphatic dysplasia. In this case, lymphatic pleural effusion and generalized edema were considered to be associated with lymphatic dysplasia. Evaluations of lymphatic abnormalities in patients with CDM have rarely been conducted. However, ultrastructural changes of lymphatic endothelial cells and fibrillar elements have been reported based on skin biopsies in adult DM patients.5 While the molecular mechanisms remain unclear, lymphatic dysplasia may contribute to lymphatic pleural effusions and edema in cases of CDM. These conditions are not uncommon in CDM, suggesting the possibility of underlying lymphatic abnormalities in patients with CDM. In the present case, pulmonary hypertension and pneumothorax were considered to be caused by pulmonary hypoplasia, which is not uncommon in patients with CDM.6 Pulmonary hypoplasia can lead to increased pulmonary vascular resistance and structural fragility of the lungs, thereby contributing to the development of pulmonary hypertension and pneumothorax. Additionally, the association of pneumothorax with other lymphatic disorders, such as lymphangioleiomyomatosis,7 raises the possibility that lymphatic dysplasia may also predispose to pneumothorax, although further investigation is needed. In conclusion, we reported a case of CDM in which the patient was diagnosed with lymphatic dysplasia using ICG lymphography. Lymphatic dysplasia should be considered in neonates with CDM who present with lymphatic pleural effusion and/or edema. Mayumi Tate and Yoshinori Aoki drafted the manuscript. Mayumi Tate, Yoshinori Aoki, Kayo Ochiai, Yoshihiko Kodama, Kazuhiko Nakame, and Yuki Kodama contributed to the patient's clinical diagnosis and treatment. Hiroshi Moritake supervised this case report and critically reviewed the manuscript. All authors read and approved the final manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Written informed consent was obtained from the patient's parents for the scientific publication of this case report. The data that support the findings of this study are available from the corresponding author upon reasonable request.