Periodontal EDS Patients May Show Rare Blood-vessel Abnormalities

Some people diagnosed with periodontal Ehlers-Danlos syndrome (pEDS) may also have vascular abnormalities, a case series highlights.

Although rare, these cases add to previous reports of vascular complications in pEDS patients and support the need for comprehensive vascular assessment in this patient population.

This information will likely help to clarify the frequency and type of these complications and to better understand the disease’s underlying mechanisms, the researchers noted.

The study, “Periodontal (formerly type VIII) Ehlers–Danlos syndrome: Description of 13 novel cases and expansion of the clinical phenotype,” was published in the journal Clinical Genetics.

Periodontal EDS is a rare form of the disease and is caused by mutations in the C1R or C1S genes, which provide instructions to produce proteins of the classical complement pathway, part of the immune system.

pEDS is mainly characterized by severe early-onset gum disease — leading to premature teeth loss — darker skin on the lower legs, and global skin fragility including abnormal scars and easy bruising.

Vascular abnormalities, mostly associated with blood arteries, have also been reported in rare pEDS cases, with a previous review study reporting a 6% frequency among these patients.

In the recent study, a team of researchers in France described 13 new cases of pEDS from seven families, of whom three patients and one relative showed vascular abnormalities. The cases included two boys (age 3 and 16 years), and 11 adults (six women and five men) with ages ranging from 21 to 74.

All patients carried mutations in the C1S or C1R genes — three of them described for the first time in the C1S gene (c.962G>C, c.961 T>G, and c.961 T>A) and considered likely disease-causative. Most cases were inherited, while three were considered sporadic, with the patient’s mutation occurring for the first time in the family.

In addition to the characteristic features of pEDS, three patients and one relative exhibited vascular complications.

A 41-year-old man, a 61-year-old man, a 74-year-old woman, and her affected maternal aunt had widespread venous insufficiency with persistent leg ulcers. Venous insufficiency occurs when blood veins in the legs have trouble sending blood back to the heart, causing blood to pool in the legs.

“We hypothesize that in these patients, skin and vascular (in particular small vessels) fragility predisposes to the occurrence of easy shin [bruising] in the context of minimal trauma, leading to leg ulceration and that the presence of venous insufficiency leads to chronicity and nonhealing of the wound, despite skin grafts,” the researchers wrote.

Considering that three of the four patients who underwent blood vein-related assessment showed venous insufficiency, these cases, combined with others previously reported, suggest that pEDS “may predispose to early onset venous insufficiency, although it does not seem to be frequent,” the team added.

In addition, a 42-year-old woman had a family history of pEDS with several relatives exhibiting potentially life-threatening abnormalities in their blood arteries. The woman herself had a brain aneurysm that did not require treatment. Two relatives in another family also had a history of serious abnormalities of the thoracic aorta, the section of the aorta that runs through the chest.

These cases confirm that vascular complications, although infrequent, can occur in people with pEDS. Based on these findings, physicians should “carry out a first complete non-invasive vascular evaluation at the time of the diagnosis in pEDS patients,” which may help early identification and initiation of appropriate care, the team wrote.

“Larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications,” the researchers wrote.

The simultaneous presence of darker skin on the legs, persistent leg ulcers, and early-onset tooth loss “should lead to the suspicion of pEDS and subsequent screening of the C1R and C1S genes,” they added.