Pycnodysostosis: Characteristics of teeth, mouth and jaws.

OBJECTIVES: To describe the clinical and radiographic oro-dental characteristics of patients with pycnodysostosis (PDO). MATERIALS & METHODS: A short interview and clinical examination of seven patients with PDO were performed as well as assessment of the temporomandibular joints and masticatory muscles using the diagnostic criteria for temporomandibular disorders, DC-TMD form. A full set of records were taken including photos and intraoral scan. Finally, existing cone beam computed tomography (CBCT) images and radiographs were also studied. RESULTS: All patients presented with bimaxillary micrognathia, five had a convex profile, and two had a straight profile. In addition, posterior open bite, Angle Class III molar relation with accompanying anterior crossbite and a grooved median palate were common findings. No patient showed symptoms of temporomandibular disorder (TMD) apart from some clicking. Finally, the main radiographic findings were the obtuse mandibular angle, the frontal bossing, the elongation of the coronoid/condylar process and the presence of hypercementosis with obliterated pulp chambers. CONCLUSION: The examined patients with PDO were characterized by dental crowding, malocclusion (anterior crossbite, posterior open bite), hypercementosis, obliterated pulp chambers and deviations in mandibular morphology. In conclusion, patients with PDO have a specific need for dental and orthodontic monitoring with focus on crowding and posterior open bite. The patients will benefit from a long-term orthodontic plan including extractions.

Obstructive sleep apnoea in pycnodysostosis: A three-dimensional upper airway analysis.

AIM: To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of the total volume (TV) with other UA morphology variables. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images of eight Danish patients with pycnodysostosis (4 males and 4 females with a mean age of 31.8 years, SD: 16.3 years) were analyzed using Mimics® (Materialise® ) and compared with a sex- and age-matched control group (6 males and 8 females with a mean age of 33.6 years, SD: 18.6 years). RESULTS: The distance from the tip of the epiglottis (E) to the Frankfurt horizontal plane (Fp) was significantly shorter in the pycnodysostosis group (P < .042). Regarding the cross-sectional measurements, at the 'maximum constriction' (P < .005), the 'upper airway limit' (P < .001) and the 'lower airway limit' (P < .035) cross-sections were significantly smaller in the pycnodysostosis group. The volumes 'nasopharynx' (P < .002) and 'total airway' (TV) (P < .01) were also significantly smaller. CONCLUSION: Patients with pycnodysostosis have a reduced total airway as well as nasopharyngeal volume compared with matched controls. Additionally, they have a reduced cross-sectional area in the upper and lower borders of the UA, and the area of maximum constriction is also reduced. These factors might explain the high prevalence of obstructive sleep apnoea in pycnodysostosis. Total airway is positively correlated with total length and cross-sections at all levels including the maximum constriction area as well as the anteroposterior dimension at the upper and lower airway borders.

Three-dimensional analysis of craniofacial morphology in patients with pycnodysostosis.

OBJECTIVE: To perform a 3D cephalometric analysis of the craniofacial characteristics of patients with pycnodysostosis and compare this with a matched control group. SETTING AND SAMPLE POPULATION: This cross-sectional descriptive study assessed eight CBCTs obtained in patients with pycnodysostosis (4 males, 4 females, mean age: 31.8 years). MATERIALS AND METHODS: Eight Danish patients with pycnodysostosis were seen at the University's Orthodontic Clinic. All CBCTs were analysed using the Mimics 21.0 software (Materialise®, Belgium) and compared with a control group (6 males, 8 females, mean age: 33.6 years). RESULTS: Interclass correlation coefficient showed excellent intra-rater reliability (> 0.93). All measurements in the 3D cephalometric analysis revealed statistical significance (P < .05) when compared with controls. Patients with pycnodysostosis generally had significantly smaller maxilla in the transverse (P < .001), sagittal (P < .002) and vertical (P < .001) dimensions. Their mandibles were also smaller vertically (P < .001) and in length (P < .001). Gonial angle was significantly larger than controls (P < .001), while mandibular volumes were considerably smaller (P < .001). CONCLUSION: Patients with pycnodysostosis have significantly smaller jaws in the vertical, sagittal and transverse dimensions compared with controls. Furthermore, the gonial angle was significantly larger, while the volume of the mandible was significantly smaller.

Genetic study of eight Egyptian patients with pycnodysostosis: identification of novel CTSK mutations and founder effect.

This is the first Egyptian study with detailed clinical and orodental evaluation of eight patients with pycnodysostosis and identification of four mutations in CTSK gene with two novel ones and a founder effect. INTRODUCTION: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia due to mutations in the CTSK gene encoding for cathepsin K, a lysosomal cysteine protease. METHODS: We report on the clinical, orodental, radiological, and molecular findings of eight patients, from seven unrelated Egyptian families with pycnodysostosis. RESULTS: All patients were offspring of consanguineous parents and presented with the typical clinical picture of the disorder including short stature, delayed closure of fontanels, hypoplastic premaxilla, obtuse mandibular angle, and drum stick terminal phalanges with dysplastic nails. Their radiological findings showed increased bone density, acro-osteolysis, and open cranial sutures. Mutational analysis of CTSK gene revealed four distinct homozygous missense mutations including two novel ones, c.164A>C (p. K55T) and c.433G>A (p.V145M). The c.164A>C (p. K55T) mutation was recurrent in three unrelated patients who also shared similar haplotype, suggesting a founder effect. CONCLUSION: Our findings expand the mutational spectrum of CTSK gene and emphasize the importance of full clinical examination of all body systems including thorough orodental evaluation in patients with pycnodysostosis.

Challenges in the orthodontic treatment of a patient with pycnodysostosis.

Pycnodysostosis is a rare, autosomal recessive syndrome characterized by osteosclerosis, brittle bones, stunting, and significant craniofacial changes. The objective of this study was to report a case of a 6-year-old patient with pycnodysostosis orthodontically treated and followed up until age 10 years and to discuss the risk factors, options for orthodontic treatment, and limitations involving this type of treatment, which has not yet been performed. Prevention through counseling and periodic follow-up visits is essential in eliminating factors that predispose patients to infections and fractures. New studies are necessary to establish safe and efficient orthodontic treatment plans.

Pycnodysostosis: review and case report.

AIM: Aim of the present study was to present a case report of a patient suffering from pycnodysostosis and assess how it may manifest and affect the dental/ orthodontic treatment. METHODS: An 11-year-old patient who was diagnosed with pycnodysostosis at the age of 18 months, attended the orthodontics department requiring treatment for extensive carious lesions, periodontal disease and severe crowding. RESULTS: After an accurate radiographic, clinical and orthodontic assessment of the patient taking into consideration the severity of the condition and the patient's necessities, we have formulated a treatment plan, which was accepted by both the patient and parents. We took into consideration the risks and benefits of the options available and the requests of the patient. CONCLUSION: We have decided to opt for the extraction of teeth to relieve the crowding as this was impeding good oral hygiene and hence increasing the risk of caries and periodontal disease. Such patients must be placed under an oral hygiene prevention scheme, a treatment plan must be accurately designed and the patient must be constantly motivated.

Rigid external maxillary distraction and rhinoplasty for pyknodysostosis.

AIM: This article reports the treatment of an 33-year-old female patient with pyknodysostosis by rigid external distraction II midface distraction system. STUDY DESIGN: The patient with pyknodysostosis described in this report had severe midfacial hypoplasia. Correction of this by use of routine orthognathic surgery would require osteosynthesis and bone grafting. Risk of infection and/or nonunion after such a surgical procedure was considered too great, and therefore the possibility of treatment by distraction osteogenesis of the maxilla was evaluated. The rigid external distraction II midface distraction system was used to relocate the hypoplastic maxilla at anterior-inferior projection. CONCLUSIONS: Distraction osteogenesis should be considered as the primary reconstructive method for maxillofacial deformities in patients with sclerosing bone dysplasias, since this is the second reported case treated successfully with rigid external distraction.

Clinical and genetic evaluation of Danish patients with pycnodysostosis.

BACKGROUND: Pycnodysostosis is a rare autosomal recessive osteosclerotic skeletal dysplasia caused by variants in the cathepsin K gene (CTSK). Clinical features include short stature, bone fragility, characteristic facial features and acro-osteolysis of the distal phalanges. Usually, patients suffer from multiple bone fractures. The purpose of this study was to describe the Danish population of pycnodysostosis patients with respect to genotype, phenotype and the prevalence of complications. We collected medical history, performed clinical examination, collected blood- and urine samples, performed dual-energy x-ray absorptiometry scan (DXA) and high-resolution peripheral quantitative computed tomography scan (HRpQCT) and obtained clinical photos. Information about complications, bone mineral density and bone markers in the blood were collected and analysed. RESULTS: Ten patients with a median age of 32 years ranging from five to 51 years participated. The pycnodysostosis phenotype varied with respect to the number of bone fractures and degree of complications. DXA and HRpQCT showed high bone mineral density. A tendency of growth hormone treatment escalating growth and increasing final height was seen. A marker of bone resorption measured in blood was within normal range in nine patients and elevated in one patient. A novel pathogenic variant in CSTK causing pycnodysostosis was detected in two related patients. Moreover information about the patients' own health perception was reported. An example being they rated their mental health to be good despite multiple bone fractures. CONCLUSION: This study provides information about genotypes and phenotypes in a Danish pycnodysostosis population. It reports new data about the complications such as bone fractures and it elucidates the levels of bone turnover markers as well as the density of the bones in one of the biggest cohort of pycnodysostosis patients ever published. An individualised approach to treatment in this patient group is necessary as the phenotype including complications varies between patients. Additional studies are needed to further understand genotype-phenotype correlations.

Use of CBCT in the orthodontic diagnosis of a patient with pycnodysostosis.

The pycnodysostosis is a genetically determined, autosomal recessive osteosclerosis, due to deficiency of cathepsin K. It is characterized by short stature, massive skull, hands and feet with short terminal phalanges, dysplastic nails. Oral and maxillofacial manifestations include hypoplasia of the mandible and maxillary sinus, obtuse mandibular gonial angle deciduous teeth and permanent impacts, or malposition, frequent overcrowding, periodontal lesions. Bone sclerosis is already detectable in X-rays during childhood, often present open fontanelles and sutures, wormian bones; frequent pathological fractures. This article presents the case of a male patient, Caucasian, age 9 years and 11 months suffer from pycnodysostosis, mutation of the gene in heterozygotes p.R241X, already followed at the Pediatric Endocrinology Clinic of the Spedali Civili of Brescia. After evaluation at the Department of Maxillofacial Surgery of the Spedali Civili of Brescia, for surgical reasons required a cone beam computed tomography (CBCT) scanner with NewTom 3G, was presented to our observation at the Department of Orthodontics of the Dental Clinic of the University of Brescia. CBCT findings including detailed information about the anatomy of the upper and lower jaw, dental elements, their relationship with the surrounding anatomical structures and the spatial position. The only radiographic examination currently available that obtains 3D images and the volume of the life-size area, without exposing patient to dose of radiation from a classic multi-layer CT is CBCT that, even through the 3D reconstructions with dedicated programs can make a correct diagnosis, prognosis and treatment in patients with maxillofacial dysmorphism. This examination allows to obtain images from around the skull that permit a complete orthodontic diagnosis, not only restricted to the area of surgical interest, taking into account the reports of the dental arches to each other and with surrounding structures.

Familial pycnodysostosis: identification of a novel mutation in the CTSK gene (cathepsin K).

BACKGROUND: Pycnodysostosis, an autosomal recessive skeletal dysplasia, is characterized by short stature, osteosclerosis, delayed cranial suture closure, hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21. PURPOSE: To describe the clinical, radiological, and molecular findings in a family with pycnodysostosis. METHODS: The CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls. RESULTS AND INTERPRETATION: We identified the novel homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense mutation leads to the substitution of the amino acid glycine at position 303 by glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation was present in affected members of the family with pycnodysostosis.

Manejo de fractura en hueso patológico en la infancia: picnodisostosis / Management of fractures in pathological bone in childhood: pycnodysostosis

La picnodisostosis es una enfermedad poco común que pertenece a las displasias esqueléticas que presentan fragilidad ósea y fracturas frecuentes. Radiológicamente se caracteriza por incremento de la densidad y fragilidad óseas. OBJETIVO: Presentar el caso de un escolar con displasia esquelética con fracturas en hueso patológico y manejo quirúrgico. CASO CLÍNICO: Escolar de sexo femenino, con antecedente de picnodisostosis detectado en etapa preescolar. Consulta posterior a caída de bicicleta con fractura de ambos fémures que se manejan quirúrgicamente con placa de compresión bloqueada.

Pycnodysostosis is a rare condition within skeletal dysplasias presenting with brittle bones and frequent fractures. Radiologically, it is characterised by increased bone density and fragility. OBJECTIVE: To present the case of a primary schoolchild with skeletal dysplasia with pathological bone fractures and their surgical management. CASE REPORT: A female primary schoolchild with a history of pycnodysostosis detected during the pre-school period. She was seen after bicycle fall that resulted in the fracture of both femurs, that were surgically managed with a locking compression plate.