The discovery raises the hope that, for the first time, it will be possible to develop targeted medical treatments capable of delaying, reversing or possibly preventing CLOVESs debilitating consequences. Importantly, it also demonstrates the potential of advanced DNA sequencing technologies for identifying the underlying molecular roots of malformation disorders that are genetic but not hereditary.
The team—led by Matthew Warman, MD, director of the Orthopedic Research Laboratories at Boston Childrens, and Kyle Kurek, MD, of the hospitals department of Pathology, and members of the hospitals Vascular Anomalies Center—reported the discovery today in the online edition of the American Journal of Human Genetics.
Some 90 children worldwide have been diagnosed with CLOVES (which stands for Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevis, Spinal/skeletal anomalies/scoliosis) since 2006, when the condition was first characterized by Boston Childrens Ahmad Alomari, MD, and investigators at the National Institutes of Health. Alomari co-directs the Vascular Anomalies Center with Steven Fishman, MD, and John Mulliken, MD; all three are authors on the paper.
The clinical features of CLOVES—in general a combination of fatty growths in the torso, vascular and skin anomalies, overgrowth in or deformities of limbs or extremities and spinal problems such as scoliosis—can vary greatly from child to child. Presently there is no cure for CLOVES, only surgical treatments aimed at alleviating symptoms or managing the syndromes progression.
Until now, the exact nature of the genetic defect or defects that cause CLOVES has remained a mystery.
"CLOVES is dynamic, presenting itself in new ways all the time, even within the same patient," said Fishman, who with Alomari and others in the Vascular Anomalies Center has treated numerous children with CLOVES. "With this discovery we are optimistic that it will now be possible to develop treatments that take less of a shotgun approach and which could prevent the syndromes progression."