Lymphedema in tuberous sclerosis complex

Am J Med Genet A. 2014 Jun;164A(6):1438-42. doi: 10.1002/ajmg.a.36469. Epub 2014 Mar 25.

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.

Keywords: edema; lymphatic abnormalities; lymphedema; tuberous sclerosis complex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Lymphedema / complications
  • Lymphedema / epidemiology*
  • Lymphedema / genetics*
  • Male
  • Middle Aged
  • Retrospective Studies
  • TOR Serine-Threonine Kinases / genetics*
  • Tuberous Sclerosis / epidemiology
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / pathology*
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*

Substances

  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases