Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24

Early Mandibular Distraction to Relieve Robin Severe Airway Obstruction in Two Siblings with Lymphedema–Distichiasis Syndrome

“…Despite the truncating FOXC2 mutation, distraction osteogenesis achieved a successful outcome in our patients, and bone repair appeared similar to that in patients with non-syndromic PRS treated at our institution [8]. Another concern arising when we decided to use distraction osteogenesis in our patients was that surgery could trigger lymphedema, as previously reported [5]. After surgery, both our patients had severe generalized edema that nevertheless responded to diuretics and fluid restriction.…”

“…O'Donnell et al in 1993 were the first to describe in a series of 24 patients, with distichiasis evaluated for cryotherapy, the association of distichiasis and PRS, but no mention was done on the functional consequence of PRS. In one family Brice and colleagues describe the father of a child with LDS who required a tracheostomy in infancy for a ''throat blockage'' [5]. Although no medical records were available they speculated that he had PRS.…”

“…Micrognathia and cleft palate have been reported in 4 % of patients with LDS suggesting that PRS may be an associated feature of LDS [5]. However, the lack of airway obstruction in most patients with LDS, micrognathia, and cleft palate, raises the question of whether the clinical manifestations in these patients are enough to fulfill the diagnosis of PRS.…”

“…For example, Temple et al, described the case of an infant with LDS presenting with cleft palate and micrognathia but no breathing problems [6]. In a large group of 18 families with LDS, Brice et al [5] described cleft palate in three boys from different families, one case associated with PRS but, again, made no mention about possible breathing problems. In 2001, Fang et al [7] identified inactivating mutations in the FOXC2 gene in two unrelated families with LDS, making molecular diagnosis possible.…”

Distichiasis without lymphoedema?

“…The confirmatory investigation is lymphoscintigraphy but false negatives can occur, 8 as can age-related false positives. In the report by Brice et al, 12 males had an earlier onset of lymphoedema and a significantly Correspondence increased risk of complications. The gene for LD, located on the long arm of chromosome 16, is that encoding FOXC2, a forkhead family transcription factor involved in numerous developmental pathways.…”