Stories about: lymphatic malformations

Another use for mTOR inhibitors: Preserving vanishing bones in Gorham-Stout syndrome

Gorham Stout rapamycin sirolimus
In Gorham-Stout, lymphatic vessels gone amok eat away at bone. Sirolimus appears to reverse this process.

The mTOR pathway is fundamental to nearly every cell in the body. It drives processes related to cell growth, protein production and metabolism, influencing everything from neurocognition to tumor growth. Because of this broad role, indications for drugs targeting the mTOR pathway are also remarkably broad.

Alexander Malloy, 14, is one of the first patients to benefit from a new use: curbing rapid bone loss in patients with a rare “vanishing bone disease,” or Gorham-Stout syndrome. It was discovered when Alex, who had mild scoliosis, started getting worse. To his parents’ shock, an MRI scan showed he was missing bones in his spine.

Gorham-Stout is actually the result of a rare vascular anomaly.

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The emerging genetic mosaic of lymphatic and vascular malformations

somatic mosaic mutations vascular anomalies vascular malformations CLOVES Klippel-Trenaunay KTS fibroadipose FAVA lymphatic malformation

Our genes can mutate at any point in our lives. In rare cases, a mutation randomly occurs in a single cell of an embryo and gets carried forward only in the descendants of that particular cell, leaving its mark in some tissues, but not in others. This pattern of mutation, called somatic mosaicsm, can have complicated consequences down the road.

Take CLOVES, a rare syndrome combining vascular, skin, spinal and bone or joint abnormalities described by Ahmad Alomari, MD, co-director of Boston Children’s Hospital Vascular Anomalies Center (VAC). Four years ago, a research team including Alomari and Matthew Warman, MD, discovered that the growths in CLOVES patients had mutations in a growth-regulating gene called PIK3CA. Those mutations, they found, were spread through the affected tissues in a somatic mosaic pattern.

Now it turns out that CLOVES is not alone. In a recent paper in the Journal of Pediatrics, VAC researchers led by Warman proved that three other rare lymphatic and vascular anomalies and overgrowth syndromes often share the same somatic mosaic PIK3CA mutations: Klippel-Trenaunay syndrome (KTS), fibroadipose vascular anomaly (FAVA) and isolated lymphatic malformations.

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