Pycnodysostosis Research Articles

Changes in Upper Airway Space in a Patient with Pycnodysostosis Following Primary Surgery and Orthodontic Treatment: A 12-Year Follow-Up Case Report

Pycnodysostosis (PDS) is an autosomal recessive form of osteosclerotic skeletal dysplasia characterized by craniofacial anomalies, a high-arched palate, and a narrowed pharyngeal space due to mandibular and maxillary deficiencies. These structural anomalies in the upper airway predispose PDS patients to obstructive sleep apnea (OSA). OSA can be managed in PDS patients using either a conservative (non-surgical and multidisciplinary) approach or surgical interventions. Given the craniofacial anomalies associated with PDS, orthodontic treatment aims to address the maxillary transverse deficit and retrognathia. Currently, there is no evidence regarding the impact of orthodontic therapy on OSA levels among PDS patients. This study reports the long-term morphological and functional changes in the upper airway of a PDS patient following adenotonsillectomy and uvulopalatoplasty at an early age (3.6 years) and orthodontic camouflage in late mixed dentition (10 years). Polysomnographies (PSGs), nuclear magnetic resonance (NMR), and lateral cephalograms taken before and after ENT surgery and orthodontic treatment were analyzed. Lateral X-rays were evaluated for changes in the posterior airway space (PAS), while polysomnographies provided the apnea–hypopnea index (AHI). The NMR scans were segmented to measure the perimeter and radius of the upper airway. The findings of this study indicate that improvements following uvulopalatoplasty (UPP) were partial and temporary. Nonetheless, orthodontic therapy and the use of elastics did not appear to influence the PAS or AHI. Future studies with larger cohorts are needed to evaluate the long-term effectiveness of the UPP procedure. This study was conducted in accordance with the CARE guidelines.

Epidural Hematoma Following Lumbar Puncture in a Child with Pycnodysostosis and Intracranial Hypertension: A Case Report

Abstract Pycnodysostosis (PDO) is a rare genetic skeletal dysplasia. Due to its rarity and clinical heterogenicity, information about its uncommon features and complications is limited. One such complication is intracranial hypertension (IH), which can be managed acutely through lumbar drainage of cerebrospinal fluid (CSF). In this report, we present the case of a 12-year-old boy with known PDO and IH who presented with worsening headache and dizziness and underwent a therapeutic lumbar puncture (LP). Two days after the LP, he experienced increasing headache and nausea. A brain computed tomography (CT) scan revealed a left frontal epidural hematoma (EDH). He was managed expectantly, and a follow-up CT scan confirmed hematoma resolution. This case presents IH as a rare complication of PDO and presents an instance where an EDH developed following an LP, which is a rare occurrence. We conclude that if LP is considered for such patients, physicians should be vigilant for the possible occurrence of intracranial hemorrhage.

Pycnodysostosis: Characteristics of teeth, mouth and jaws.

To describe the clinical and radiographic oro-dental characteristics of patients with pycnodysostosis (PDO). 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. 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. 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.

Clinical and radiographic characteristics of pycnodysostosis: A systematic review.

Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial manifestations. This review represents a systematic examination of these manifestations, as well as oral features associated with PYCD. A systematic review was conducted across 8 databases from February to March 2023. The search strategy focused on studies reporting cases of PYCD that examined the clinical and radiographic craniofacial and oral characteristics associated with this syndrome. The review included 84 studies, encompassing a total of 179 cases of PYCD. More than half of the patients were female (55.3%), and the mean age was 14.7 years. Parental consanguinity was reported in 51.4% of the cases. The most common craniofacial clinical manifestation was a prominent nose, observed in 57.5% of cases. Radiographically, the most frequently reported craniofacial characteristics included the presence of an obtuse mandibular angle (84.3%) and frontal cranial bosses (82.1%). Clinical and radiographic examinations revealed oral alterations, with micrognathia present in 62.6% of patients and malocclusion in 59.2%. Among dental anomalies, tooth agenesis was the most commonly reported, affecting 15.6% of patients. Understanding the clinical and radiographic craniofacial features of PYCD is crucial for dental professionals. This knowledge enables these clinicians to devise effective treatment plans and improve patient quality of life.

Orthopedic Treatment of Pycnodysostosis: A Systematic Review.

Pycnodysostosis (PYCD) is an autosomal recessive lysosomal storage disorder of the bone which leads to stereotypical abnormalities consisting of, but not limited to, sclerotic and fragile bone, shortened distal phalanges, and obtuse mandibular angle. Current literature describes the otolaryngological manifestations and treatment of this disorder; however, the treatment of orthopedic fractures in PYCD patients is seldom described and remains a controversial topic. We aim to systematically review the current evidence regarding the optimal treatment of PYCD patients with fractures.We performed a literature search using PubMed, MEDLINE, Web of Science, and Google Scholar databases. Elig­ibility criteria consisted of English-language literature of PYCD patients undergoing treatment for orthopedic surgery fractures. Non-English papers or literature focused on maxillofacial manifestations/treatment were excluded.The database search resulted in the identification of 500 articles. After removing duplicates and enforcing our inclusion criteria, 29 case reports/series (40 patients) were included. The average age was 31.25 (­±18.2) years, with 57.5% of patients being female. Overall, 62.5% of patients had consanguineous parents. Additionally, 86.2% reported a history of previous fractures while 47.5% reported a spontaneous or minor trauma fracture, with most fractures occurring in the femur (60.0%) and tibia (40.0%). Radiographic features consisted of densification in the femur 45.0% (18/40), tibia 37.5% (15/40), and spine 25.0% (10/40). Overall, 84.2% of patients were treated with surgical management consisting of internal plate fixation (IPF) (48.3%), intramedullary fixation (20.7%), and Ilizarov external fixation (IEF) (13.8%). Overall, the refracture rate was 25.0% and was lowest in intramedullary fixation (0/6), compared to IPF (3/14) and IEF (3/4). Average time until refracture was 40.6 months (3-132 months).Long-term follow-up is recommended in patients with PYCD due to the propensity for fractures/refractures. While this study provides the groundwork for the treatment of PYCD patients, further research with higher-evidence studies should be conducted to establish the optimal orthopedic treatment of this disorder.

OSTEOMYELITIS IN A PATIENT WITH PYCNODYSOSTOSIS: A RARE CASE REPORT AND REVIEW OF THE LITERATURE

Pycnodysostosis (PYCD) is a rare autosomal recessive disease occurring due to a mutation in the gene that codes for the enzyme cathepsin K. Osteomyelitis of the jaws is a common complication of the PYCD. A 30-year-old female patient with PYCD presented with mandibular osteomyelitis which was treated by sequestrectomy and with a buccal fat pad as free graft (BFPFG) to fill the bone defect. The 24-month of follow-up demonstrates clinical and radiographic healing. A literature search was undertaken in Medline (through PubMed) in March of 2018 on PYCD case reports. Seventeen contributions were included in this study and discussed. To the best of our knowledge, this is the first case using BFPFG in the management of osteomyelitis of the jaws in a patient with PYCD. Despite the good results, further studies using BFPFG as adjuvant therapy for the management of jaw osteomyelitis are necessary to elucidate its clinical efficiency and safety. Support: FAPEMIG.

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia.

Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

An Update on Osteomyelitis Treatment in a Pycnodysostosis Patient

The aims of the present study were to discuss the demographic distribution and clinical characteristics of patients with pycnodysostosis (PYCD) and the onset of osteomyelitis and its treatment using a literature review. The authors also report on an update of treatment of mandibular osteomyelitis in a patient with PYCD using a buccal fat pad (BFP) as a free graft. The study was carried out in 2 steps. In the first step, an electronic search was undertaken in PubMed in March 2018, with 17 articles being included. In the second step, the authors present a case of mandibular osteomyelitis in a 30-year-old woman with PYCD treated by sequestrectomy and a BFP as a free graft (follow-up, 24months). Twenty-one cases of osteomyelitis of the jaws in patients with PYCD were included. Dental extraction, mandibular fracture, and 1 case of facial trauma represented the causes of mandibular osteomyelitis. Treatments included resection associated with antibiotics and sequestrectomy alone or associated with antibiotics. Despite the good results of the present case, further studies using the BFP as an adjuvant for jaw osteomyelitis are necessary to elucidate its clinical efficiency and safety.

Clinical and Radiographic Features of Pycnodysostosis with Emphasis on Dentofacial Problems

Pycnodysostosis (PDO) is a rare genetic disorder characterized by cathepsin K deficiency which plays an important role in bone metabolism. Among clinical features of this disease which are mainly caused by altered bone remodeling are craniofacial abnormalities such as hypoplastic maxilla and obtuse gonial angle which consequently lead to respiratory insufficiency in forms of pharyngeal narrowing and severe snoring. In this paper, another case of this rare disorder is presented along with a review on etiology and management issues of respiratory insufficiency in these patients.

A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis.

Deficiency of cathepsin K (CTSK), a lysosomal cysteine protease, has been shown earlier as a cause of an autosomal recessive osteosclerotic skeletal dysplasia pycnodysostosis. The objective of the present study was to identify the potential sequence variants in CTSK gene in a large consanguineous Pakistani family with pycnodysostosis. Genotyping of 4 affected and 6 unaffected members of the family was performed using polymorphic microsatellite markers linked to CTSK gene on chromosome 1q21. To screen for pathogenic mutation, exons and splice junctions of CTSK gene were polymerase chain reaction amplified from genomic DNA and sequenced directly in an automated DNA sequencer. Microsatellite analysis showed linkage of the family to CTSK gene on chromosome 1q21. Sequence analysis revealed a novel missense mutation c.728G>A (p.G243E) in exon 6 of the CTSK gene. A novel missense mutation was identified in CTSK gene in a Pakistani family with 5 individuals affected with autosomal recessive pycnodysostosis.

Pycnodysostosis with a patella fracture

A 33-year-old woman was admitted to hospital with an injured right knee. She had a history of fractures and been previously diagnosed with osteopetrosis. She was 136 cm tall with short digits, fl at and grooved nails, and all the facial characteristics of pycnodysostosis. Results of laboratory tests showed no evidence of anaemia. Radiography revealed a patella fracture with increased bone density and acro-osteolysis of the distal phalanges (fi gure A, B). She was diagnosed with pycnodysostosis on the basis of clinical and radiological fi ndings. Surgical repair was undertaken, and low-intensity pulsed ultrasound treatment was initiated postoperatively. Bony union was confi rmed with full range of active knee motion 15 months after surgery. Pycnodysostosis is an autosomal recessive lysosomal storage disorder caused by a mutation in the gene encoding the enzyme cathepsin K. Features of pycnodysostosis include short stature and acroosteolysis. Laboratory results showing no evidence of anaemia can help to diff erentiate pycnodysostosis from osteopetrosis. Pathological fractures of long bones are characteristic of pycno dysostosis, whereas patella fractures are extremely rare.

PYKNODYSOSTOSIS

Pyknodysostosis (PKD), also called Maroteaux-Lamy disease or Toulouse-Lautrec syndrome is a rare osteosclerosing skeletal disorder that has an autosomal recessive trait. It is characterized by short stature, brachycephaly, short stubby fingers, open cranial sutures and fontanelles, diffuse osteosclerosis with attendant multiple fractures of long bones and osteomyelitis of the jaw; but with rare visceral manifestations. In this article we present three cases of PKD with diverse classical clinico-radiological features. Worldwide PKD have been reported in 9-months to 55 years but remarkably, we have presented amongst the youngest diagnosed cases, at 8months with visceral manifestations. Understanding early and delayed clinic-radiological manifestations of PKD is very important as accurate diagnosis of PKD avoid misdiagnosing it as hydrocephalous, cleidocranial dysostosis and osteopetrosis as the conditions may resemble each other clinically and radiologically.

Mandibular Reconstruction With Autogenous Graft in Patient Presenting Pyknodysostosis: Case Report

Pyknodysostosis (PKND) is a rare autosomal recessive skeletal disease, first described by Maroteaux and Lamy in 1962. The term “pyknos” comes from Greek, which means dense or thick and characterizes a syndrome involving continuous bone tissue formation without subsequent resorption.1

Pycnodysostosis: An Early Case Report With Emphasis On The Radiographic Findings

Pyknodysostosis (PKND) is a rare sclerosing bone disorder, characterized with generalized diffuse osteosclerosis. The head is usually large with fronto-parietal bossing and open fontanelles, hypoplastic malar and maxillary bones. We report a case of PKND in a 4-year-old male child, first referred for evaluation with a possible diagnosis of osteopetrosis, because of his multiples members and clavicles fractures. We describe the clinical findings, dentomaxillofacial radiologic exams and differential diagnosis from osteopetrosis.

Maxillary distraction osteogenesis in a patient with pycnodysostosis: a case report

Pycnodysostosis (PDO) is a rare autosomal recessive inherited disease belonging to the group of craniotubular bone dyplasias. The bone metabolism is abnormal due to malfunction of the osteoclasts with a decreased bone remodeling, which usually leads to sclerotic and fragile bones.1 Genetic research has located mutations in the cathepsin K gene positioned on chromosome 1q21 in patients with PDO.2

Picnodisostose: relato de dois casos

Picnodisostose (PYCD) é uma rara displasia esquelética autossômica recessiva, decorrente de defeito no gene codificador da enzima catepsina K, caracterizada por baixa estatura (BE), osteoesclerose, acroosteólise, deformidades crânio-faciais e fragilidade óssea. Embora a BE seja característica, deficiência de GH tem sido relatada apenas em parte dos casos de PYCD. Apresentamos dois casos isolados, com quadros clínico-radiológicos característicos. Caso 1: 9 anos, masculino, pais consangüíneos, apresentando BE, osteoesclerose, fragilidade óssea, exoftalmia bilateral, fronte ampla, braquicefalia, alargamento das suturas cranianas, fontanelas abertas, micrognatia, implantação anormal dos dentes, braquidactilia, unhas distróficas e acrosteólise das falanges distais. Caso 2: 17 anos, masculino, com BE, nariz proeminente, braquicefalia, plastibasia, falha de fechamento de suturas e fontanelas, hipoplasia mandibular, dentição anormal, osteoesclerose difusa, braquidactilia, acrosteólise das falanges distais e aumento das pregas cutâneas nas mãos. Ambos apresentaram níveis basais normais de TSH, T4 livre, gonadotrofinas e testosterona, e da resposta do GH e do cortisol, durante teste farmacológico. Em conclusão, a PYCD parece ser uma condição heterogênea com apresentação clínica variável. Assim, embora não tenha sido observado nestes casos, mas tendo em vista as descrições prévias, consideramos importante que pacientes com PYCD sejam rotineiramente submetidos à avaliação hormonal.

Pycnodysostosis: Toulouse-Lautrecís and Aesopís disease?

Pycnodysostosis: Toulouse-Lautrecís and Aesopís disease?

Novel Mutations of the Cathepsin K Gene in Patients with Pycnodysostosis and Their Characterization

Novel Mutations of the Cathepsin K Gene in Patients with Pycnodysostosis and Their Characterization

PYCNODYSOSTOSIS: MAPPING AND EVALUATION OF THREE CANDIDATE GENES.† 854

Pycnodysostosis (PYCNO) is an autosomal recessive sclerosing skeletal dysplasia of unknown etiology. Initially, we demonstrated linkage of PYCNO to chromosome 1q21 in a large Arab family in which only marker D1S498 failed to recombine with the disease (Nature Genetics,10:235). Recently, the PYCNO critical region was refined to a 2 cM interval from D1S2344 to D1S2343/D1S2347. We report the evaluation of three candidate genes for PYCNO which had been mapped to 1q21: the interleukin-6 receptor (IL6R), MCL1 which is a BCL2 homolog, and cathepsin S (CTSS). Sequence-tagged sites were developed for these three PYCNO candidate genes and tested against the Stanford G3 diploid radiation hybrid panel. Analysis of the data with the RHMAP software package revealed that IL6R was tightly linked to D1S305, excluding it from the PYCNO critical region. MCL1 and CTSS were linked to D1S498 and D1S2347, placing them within the critical region. In order to search for disease-causing mutations, PCR amplification and sequencing of MCL1 and CTSS exons and their exon-intron boundaries from genomic DNA of three PYCNO families were carried out. A polymorphism resulting from a single base pair substitution for CTSS was found but no putative disease-causing mutations were detected in either MCL1 or CTSS. CTSS protease activity in cultured lymphoblasts from unrelated PYCNO patients also was determined and was normal. The absence of coding region mutations and the presence of normal protease activity for CTSS effectively excludes its candidacy. While promoter and other mutations have not been excluded for MCL1, the lack of coding region mutations in three separate PYCNO families makes it an unlikely candidate. Current efforts are directed towards further refining the PYCNO critical region with additional families and developing the physical map of that region.