Lymphedema in tuberous sclerosis complex

Abstract

Congenital lymphedema has been described as a possible rare association of tuberous sclerosis complex (TSC), with only six previous cases reported in the literature. TSC is an autosomal dominant, multisystem disorder connected to aberrant regulation of the mammalian target of rapamycin (mTOR) pathway. The aim of this study is to review cases of lymphedema in a large cohort of TSC patients. The medical records of 268 patients seen at The Herscot Center for Children and Adults with Tuberous Sclerosis Complex at the Massachusetts General Hospital from 2002 to 2012 were retrospectively reviewed for reports of lymphedema or edema of unknown etiology. Genotypic and phenotypic data were collected in accordance with institutional review board (IRB) approval. This cohort presents two new cases of congenital lymphedema in TSC patients and acquired lymphedema was found in eight additional cases. Thus, we report 10 new cases of lymphedema in TSC (4%). The two patients with congenital lymphedema were female, as were the previous six reported cases. The frequency of lymphedema reported here (4%) is higher than the estimated prevalence in the general population (0.133-0.144%), suggesting a higher frequency of lymphedema in TSC. This study shows that patients with TSC and lymphedema are more likely to be females with renal AMLs and suggests that congenital lymphedema is a gender-specific (female) manifestation of TSC. Exploration of the potential role of mTOR antagonists may be important in treatment of lymphedema in TSC patients.

Tuberous Sclerosis Complex Associated with Vascular Anomalies or Overgrowth

“…TSC with lymphedema and vascular dysplasia (manifesting as large‐vessel stenosis or aneurysm) has been reported . There are four reports of solitary limb overgrowth , three with vascular anomalies in conjunction with TSC (Table , patients 1–4) .…”

Less common manifestations in TSC

“…This may be related to hormonal influences, as found in other genderbiased manifestations of TSC, including LAM or renal angiomyolipomas (Geffrey, Shinnick, Staley, Boronat, & Thiele, 2014;Hoshiai, Oguma, Sato, Konishi, & Minami, 2015;Navarre & Poitras, 2014;Tan, Tamblyn, & Hinds, 2017).…”

“…A study including children and adults with TSC found lymphedema in 10 out of 268 patients (4%), and two of those were congenital (Geffrey et al, 2014). A study including children and adults with TSC found lymphedema in 10 out of 268 patients (4%), and two of those were congenital (Geffrey et al, 2014).…”

Indocyanine green lymphography for congenital lymphatic dysplasia with tuberous sclerosis complex: A case report

“…Tuberous sclerosis complex (TSC) is an autosomal‐dominant, multisystem disorder characterized by benign hamartomas in multiple organ systems. Congenital lymphedema has been described as a possible rare association of TSC . However, there have been very limited reports of imaging evaluation of this clinical condition, and no report of imaging study regarding lymphedema in infants with TSC.…”

“…Congenital lymphedema has been described as a possible rare association of TSC . However, there have been very limited reports of imaging evaluation of this clinical condition, and no report of imaging study regarding lymphedema in infants with TSC. We evaluated lymphatic function in an extremely low birthweight infant with TSC, using indocyanine green (ICG) lymphography to diagnose and assess the severity of lymphatic dysplasia.…”