Person:

Greene, Arin

Macrodactyly is a rare family of congenital disorders characterized by the diffuse enlargement of 1 or more digits. Multiple tissue types within the affected digits are involved, but skeletal patterning and gross morphological features are preserved. Not all tissues are equally involved and there is marked heterogeneity with respect to clinical phenotype. The molecular mechanisms responsible for these growth disturbances offer unique insight into normal limb growth and development, in general. To date, no genes or loci have been implicated in the development of macrodactyly. In this study, we performed the first transcriptional profiling of macrodactyly tissue. We found that pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly samples. The mitogenic functions of PTN correlate closely with the clinical characteristics of macrodactyly. PTN thus represents a promising target for further investigation into the etiology of overgrowth phenotypes.

Summary: Lymphedema results from abnormal development or injury to the lymphatic system. One-fourth of patients with lower extremity enlargement are erroneously labeled with “lymphedema.” We describe a patient with hypothyroidism who developed soft-tissue overgrowth of her foot. She was referred to our Lymphedema Program for management of “lymphedema” and overgrown toes. The patient’s lymphoscintigram showed normal lymphatic function in her extremities, and she was diagnosed with myxedema by histopathology. Nodular localized myxedema should be included in the differential diagnosis of lymphedema.

Summary: Obesity increases the risk of upper extremity lymphedema following treatment for breast cancer and can cause lower extremity lymphatic dysfunction in extremely obese individuals. We report the first patient with obesity-induced upper extremity lymphedema. A 62-year-old man with a previous body mass index (BMI) of 105.6, presented with a BMI 60.3 following weight loss. He complained of lymphedema of all 4 extremities, which was confirmed by lymphoscintigraphy. Because the upper limbs are more resistant to lymphedema than the lower extremities, a higher BMI threshold may be necessary to cause upper extremity lymphatic dysfunction.

Summary: Lymphedema is the progressive enlargement of tissue due to inadequate lymphatic function. Obesity-induced lymphedema of the lower extremities can occur once a patient’s body mass index (BMI) exceeds 50. We report our first patient with obesity-induced lower extremity lymphedema who was followed prospectively before and after weight loss. A 46-year-old woman with a BMI of 80 presented to our Lymphedema Program complaining of bilateral lower extremity swelling. Lymphoscintigraphy showed impaired lymphatic drainage of both lower extremities consistent with lymphedema. She was referred to a bariatric surgical weight-loss center and underwent a sleeve gastrectomy. After reaching her new steady-state BMI of 36 eighteen months following her procedure, lymphoscintigraphy showed no improvement in lower extremity lymphatic function. Patients at risk for obesity-induced lymphedema should be counseled that they should seek weight-loss interventions before their BMI reaches 50, a threshold at which point lower extremity lymphedema may occur. Unlike other comorbidities that reverse following massive weight loss, obesity-induced lymphedema may not resolve.

Summary: Primary lymphedema is a rare, progressive disease that typically affects the lower extremity. The condition is not curable, and the limb enlarges over time because of subcutaneous fibroadipose deposition. We present a patient with clinical and radiographical evidence of resolution of primary lymphedema. This observation may provide greater insight into the pathophysiology of the disease.

Background: Primary lymphedema and capillary malformation are independent vascular malformations that can cause overgrowth of the lower extremity. We report a series of patients who had both types of malformations affecting the same leg. The condition is unique but may be confused with other types of vascular malformation overgrowth conditions (eg, Klippel–Trenaunay and Parkes Weber). Methods: Our Vascular Anomalies Center and Lymphedema Program databases were searched for patients with both capillary malformation and lymphedema. Diagnosis of lymphedema–capillary malformation was made by history, physical examination, and imaging studies. Because lymphedema–capillary malformation has phenotypical overlap with other conditions, only patients who had imaging confirming their diagnosis were included in the analysis. Clinical and radiological features, morbidity, and treatment were recorded. Results: Eight patients (4 females and 4 males) had confirmed lymphedema–capillary malformation. Referring diagnosis was Klippel–Trenaunay syndrome (n = 4), diffuse capillary malformation with overgrowth (n = 3), or lymphatic malformation (n = 1). The condition was unilateral (n = 6) or bilateral (n = 2). Morbidity included infection (n = 6), difficulty fitting clothes (n = 6), bleeding or leaking vesicles (n = 5), leg length discrepancy (n = 4), and difficulty ambulating (n = 3). All patients were managed with compression regimens. Operative management was liposuction (n = 3), treatment of phlebectatic veins (n = 3), staged skin/subcutaneous excision (n = 1), and/or epiphysiodesis (n = 1). Conclusions: Lymphedema and capillary malformation can occur together in the same extremity. Both conditions independently cause limb overgrowth primarily because of subcutaneous adipose deposition. Compression garments and suction-assisted lipectomy can improve the condition. Lymphedema–capillary malformation should not be confused with other vascular malformation overgrowth diseases that have different morbidities and treatments.