*3.4.1 Etiology and pathogenesis*

pEDS was be caused by heterozygous mutations in complement 1 subunit genes *C1R* and *C1S* [67], and our understanding of the pathophysiological mechanisms underlying these conditions remains very limited. Experimental evidence suggests that it is linked to secretion or release of active C1r serine protease in the extracellular space. This mechanism may cause gingival hyperinflammation in response to mild biofilm accumulation, and subsequently rapidly progressing periodontal destruction [68].

### *3.4.2 Clinical manifestations*

A systematic review was conducted in 2017 about the clinical manifestations of pEDS, and **Table 3** shows the clinical features in 93 pEDS patients with *C1R*/*C1S* mutation [64, 66].


**Table 3.**

*Clinical features of periodontal Ehlers-Danlos syndrome (pEDS).*

*Periodontal Disease Associated with Genetic Disorders DOI: http://dx.doi.org/10.5772/intechopen.97497*

Typical clinical features of pEDS are:


#### **Figure 14.**

*Oral manifestations of periodontal Ehlers-Danlos syndrome (pEDS) patients with serious periodontitis. Left panels (set of nine intra-oral photographs) were from a Chinese male, 24 years with pEDS; right panels were from of his mother who also suffered from pEDS [69].*

#### **Figure 15.**

*Orthopantomographs (OPG) of pEDS patients with severe alveolar bone loss, atrophic edentulous ridges. A1, A2, A3 were OPG images from the Chinese male (Figure 14, left panels) with pEDS in 2008, 2012 or 2017. B1 and B2 were OPG images of his mother with pEDS (Figure 14, right panels) in 2008 or 2017. C was OPG image from the affected maternal uncle who also has pEDS in 2017 [69].*

#### **Figure 16.**

*Dermatological manifestations of pEDS. A and C were that of the Chinese male with pEDS (Figure 14, left panels); B was his mother (Figure 14, right panels) with pEDS [69].*

#### *3.4.3 Diagnosis*

In the 2017 classification of Ehlers–Danlos syndromes, clinical criteria suggestive for pEDS were defined. Three major criteria and one of the minor criteria must be fulfilled [63].

Major criteria are (1) childhood or adolescence onset severe, intractable periodontitis, (2) thin/atrophic attached gingiva, (3) pretibial pigmented scars, and (4) a first-degree relative in family who also meets pEDS clinical criteria.

Minor pEDS diagnostic criteria include easy bruising, joint hypermobility (typically distal joints), skin hyperextensibility and fragility, atypical scarring, proneness to infections, hernias, marfanoid facial features, acrogeria, and prominent vasculature.

A clinical diagnosis of pEDS should be confirmed with genetic testing. pEDS was caused by dominant gain of function mutations in *C1R* or *C1S*.

#### *3.4.4 Treatment*

There is no curative treatment for pEDS. Conservative treatments were offered including oral hygiene instruction, periodontal maintenance about every 3 months or more frequently as the dentist/periodontist sees fit, systemic antibiotics, removable dental prostheses, skin sparing, injury or wound avoidance, emotional support. pEDS patients were reported to have high risk of peri-implant disease also so intense implant maintenance is mandatory [63, 64, 70].

#### *3.4.5 Genetic counseling*

Transmission is autosomal dominant. Genetic counseling should be offered to the parents of an affected individual informing them of the 50% chance that their offspring could inherit the disease.

#### *3.4.6 Prognosis*

Despite meticulous dental care, pEDS patients eventually become edentulous at an early age (mean age 20 years; range 14–48 years). Life expectancy of pEDS individual is otherwise same as their unaffected counterparts [63, 64, 66].
