Update of dental and maxillofacial alterations in patients with pycnodysostosis

Pycnodysostosis is a rare, autosomal recessive genetic condition, which causes a decrease in bone remodeling, resulting in different clinical and radiographic manifestations. This case series aims to describe two clinical cases diagnosed at the Department of Oral and Maxillofacial Surgery and Traumatology of a University on the Northeast of Brazil. There are two complex cases involving osteomyelitis and dental and bone alterations of the jaws. It is concluded that the knowledge of oral and maxillofacial characteristics of this syndrome are required to plan appropriate treatment for patient in order to avoid complications of dental treatments due to inadequate bone remodeling.

introDuCtion Pycnodysostosis was described in 1962 by Maroteaux & Lamy. Also called Toulouse-Lautrec syndrome (1) , it is a rare, autosomal recessive inherited disorder caused by mutation in the gene encoding the cathepsin K enzyme (2) . It can be related to inbreeding between the parents in 30% of cases, with no gender predilection; causes lower bone remodeling, which results in several clinical and radiographic manifestations (3) .
Clinical manifestations of this disease include short stature, generalized sclerotic bone, stunted extremities, and adult height ranging from 134 to 152 cm. The most frequently oral manifestations observed are maxillary atresia, increased angle of the mandible, enamel hypoplasia, increased risk of pathological fractures during dental surgery and tooth extraction due to bone fragility. However, despite the fragility, bone healing is normal. The onset of osteomyelitis related to a tooth with large carious lesion is frequent (4) . These findings reinforce the importance of diagnosing the abnormality for appropriate dental planning of patients, taking necessary precautions.
Radiographic findings include osteosclerosis, wide open cranial sutures and fontanelles, absence of pneumatization of the facial sinuses, and increased radiopacity of all bones (especially the vertebral column), long bones and base of the skull. The disease is often diagnosed at an early stage in patients with short stature and open anterior fontanelle. When identification is late, it is due to bone fracture conditions (2) .
One of the major aspects that require the oral surgeon attention is the need to carefully plan surgical interventions due to defective bone turnover to minimize the risk of osteomyelitis or osteonecrosis (3) .
Our study proposes to report two distinct cases of pycnodysostosis syndrome, associating clinical and radiographic characteristics and elucidating clinical management to avoid complications resulting from poor bone remodeling. In addition, a Medline mapping survey of existing cases was conducted from 1962 to 2018.

CaSE rEPort
Case 1 A male patient with pycnodysostosis syndrome sought the Oral and Maxillofacial Surgery and Traumatology service of the Universidade Federal do Rio Grande do Norte (UFRN) with short stature, large hands with short spoon-shaped phalanges, dystrophic nails and history of repeated fractures in the left tibia, associated with low-impact trauma ( Figure 1A-B). Intraoral examination revealed ogival palatal, maxillary atresia, rotated teeth and open mandibular angle ( Figure 1C-E).

Case 2
A female patient with pycnodysostosis syndrome attended at the Oral and maxillofacial Surgery and Traumatology service of the UFRN presenting short stature, large hands with short spoonshaped phalanges (Figure 2A-B), rotated teeth, dental enamel hypoplasia ( Figure 2C) and bilateral osteomyelitis of the body of the mandible ( Figure 3). She reported painful and pulsating symptoms. The partially dentate patient presented process of local infectious with active drainage and bilateral submandibular fistula Update of dental and maxillofacial alterations in patients with pycnodysostosis
Osteomyelitis is the most severe oral complication of pycnodysostosis due to previous dental extractions or infections. The authors speculate that inappropriate bone remodeling with osteoclast dysfunction does not prevent bone deposition, however causes fragile bone formation and reduced vascularization, worsening with age. The greater susceptibility to osteomyelitis due to the decrease in the number of osteons and the large obliteration of Havers canals impairs blood flow through the vessels, increasing the infection (20) . Our patient underwent previous dental extraction and presented history of pericoronitis on the contralateral side.
Another common finding is enamel hypoplasia, which plays an important role in oral health. Areas of enamel demineralization are likely to cavities, so proper care must be taken to prevent them. Good oral hygiene, clinical evaluation and periodic radiographic examinations are recommended (8,10,20) .
Hypercementosis occurs due to the increase of cementocytes and cementoblasts between the cementum layers, which suggests a hypocalcified cementum feature demineralization. This may be caused by improper collagen degradation. Cement consists 90% of I, III and ground substance (6) .
The bite pattern of patients is predominantly class III due to the atypical horizontal insertion of the mandibular condyle into the glenoid fossa; such a pattern tends to project the mandible forward (20) .
In the reported cases, we observed short stature with stunted extremities, shortened phalanges, biprotrusion, bilateral open bite and dental crowding. In addition to these characteristics, case 2 presented amelogenesis imperfecta and osteomyelitis secondary to dental extraction. Several bone diseases should be considered in the differential diagnosis of pycnodysostosis, especially cleidocranial dysostosis, acroosteolysis, osteogenesis imperfecta and osteopetrosis (4) . In cleidocranial dysostosis, the clavicle is often affected; in pycnodysostosis, this bone is not affected (21) . The absence of the mandibular angle is fundamental to distinguish pycnodysostosis from acroosteolysis (22) .
It is concluded that knowledge of the oral and maxillofacial characteristics of pycnodysostosis syndrome is necessary to plan the appropriate treatment for the patient in order to avoid complications resulting from previous tooth extractions, caries, periodontal disease and orthodontic appliance installation, since bone repair of these patients is hampered by inadequate bone remodeling.