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Journal of Orthopaedics 2019Pycnodysostosis is an autosomal recessive disease caused by a gene mutation leading cathepsin K deficiency. Pathological fractures of the long bones are common, but...
Pycnodysostosis is an autosomal recessive disease caused by a gene mutation leading cathepsin K deficiency. Pathological fractures of the long bones are common, but guidelines on fracture treatment in these patients are still lacking. We have treated 5 fractures in 2 pediatric pycnodysostosis patients. We hypothesize that pycnodysostosis patients have an incomplete remodeling process in fracture healing because of cathepsin K deficiency. Therefore, to minimize the role of endochondral bone formation (indirect) after a fracture, it seems prudent to strive for direct bone healing (intramembranous) instead of indirect bone healing. Open reduction with internal fixation should be the goal.
PubMed: 31048950
DOI: 10.1016/j.jor.2019.03.022 -
JFMS Open Reports 2022A 9-month-old entire male domestic longhair cat presented with a history of pathological fractures, chronic musculoskeletal pain and poor growth. Multiple facial and...
CASE SUMMARY
A 9-month-old entire male domestic longhair cat presented with a history of pathological fractures, chronic musculoskeletal pain and poor growth. Multiple facial and skeletal abnormalities were identified on physical examination and advanced imaging (CT and radiographs). A variant in was identified in the affected cat following whole-exome sequencing (WES). The cat was managed symptomatically with diet, environmental modifications and analgesia.
RELEVANCE AND NOVEL INFORMATION
This is the first report of a cat with a similar clinical presentation and genetic variant to the hereditary human genetic disorder pyknodysostosis. In this case, WES was performed, which often facilitates the diagnosis of various hereditary disorders (ie, a conceptual framework for practicing feline genomic medicine). Despite the severe skeletal and appendicular abnormalities described, the cat was alive more than 2 years after its initial presentation.
PubMed: 36532681
DOI: 10.1177/20551169221137536 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Pycnodysostosis is an inherited autosomal recessive disorder characterized by dysplasia of the skeletal system. It occurs in any human races with no disparity in gender...
Pycnodysostosis is an inherited autosomal recessive disorder characterized by dysplasia of the skeletal system. It occurs in any human races with no disparity in gender or age predilection. The disease is diagnosed at a young age owing to the frequent fragile bone fractures. Craniofacial and dental manifestations may overlap with those of other craniofacial dysostosis; therefore, precise knowledge is essential in differential diagnosis as it may affect the treatment outcome. Here, we report three cases with typical clinical and radiological features, among which one presented with osteomyelitis of the mandible.
PubMed: 38882744
DOI: 10.4103/jpbs.jpbs_1203_23 -
Intractable & Rare Diseases Research Aug 2014Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short...
Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acroosteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Patients usually present with short stature or dysmorphic features the Pediatric Endocrinology or Genetics clinics, with atypical fractures to the orthopedics clinics or hematological abnormalities to the hematology clinics. However, under-diagnosis or misdiagnosis of this condition is a major issue. Pycnodysostosis is not a life threatening condition, but craniosynostosis, frequent fractures, respiratory-sleep problems, and dental problems may cause significant morbidity. Although no specific treatment for this disorder has been described, patients should be followed for complications and treated accordingly. A specific treatment for the disorder must be established in the future to prevent complications and improve quality of life for patients in the current era of advanced molecular research.
PubMed: 25364650
DOI: 10.5582/irdr.2014.01014 -
Hormones (Athens, Greece) 2002
PubMed: 17018457
DOI: No ID Found -
European Journal of Medical Genetics Feb 2024Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and... (Review)
Review
Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in CTSK gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing. We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of CTSK gene revealed the presence of the pathogenic homozygous variant c.746T>A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis. We also review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature. This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.
Topics: Female; Humans; Middle Aged; Fractures, Spontaneous; Mandible; Mandibular Fractures; Pycnodysostosis; Quality of Life
PubMed: 38141876
DOI: 10.1016/j.ejmg.2023.104904 -
Journal of Orthopaedic Case Reports 2016Pycnodysostosis is a rare genetic disease characterized by osteosclerosis and bone fragility. The clinical aspects are varied including short stature, acro-osteolysis of...
INTRODUCTION
Pycnodysostosis is a rare genetic disease characterized by osteosclerosis and bone fragility. The clinical aspects are varied including short stature, acro-osteolysis of distal phalanges, and dysplasia of the clavicles. Oral and maxillofacial manifestations of this disease are very clear. The head is usually large, a beaked nose, obtuse mandibular angle, and both maxilla and mandible are hypoplastic. Dental abnormalities are common. We report a case with the typical clinical and radiological characteristics of the Pycnodysostosis associated with a conductive hearing loss, an association rarely reported.
CASE PRESENTATION
A 12-year-female was admitted in our institute for short stature with a dysmorphic facies for evaluation. The patient reported a history of multiple fractures of the long bones after a trivial fall. On physical examination, she had the following features: short stature, limited mouth opening, short hands and feet with dysplastic nails; frontal and occipital bossing; and hypoplasia of the maxilla and mandible. Examination of the mouth: grooved palate, caries of the teeth, impacted and malposed teeth, persistent deciduous teeth and missing teeth. Laboratory investigations were normal. The radiographic examination showed a generalized increase in the bone density, slight condensation of the skull base and a very open mandibular angle. X-rays showed tapered phalanges with acro-osteolysis of the distal phalanges. A symptomatic treatment was proposed based on fracture prevention, oral hygiene, frequent dental visits and psychiatric support.
CONCLUSION
The clinical and radiological features are the bases for the diagnosis of this disease. It is important to make the diagnosis as early as possible in order to plan the treatment and to provide a better life quality to the patients.
PubMed: 27703936
DOI: 10.13107/jocr.2250-0685.426 -
Frontiers in Oral Health 2023Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral...
Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral manifestations are commonly described and include a high-arched palate with dental crowding and malocclusion, hypoplastic enamel, and retained deciduous teeth with impacted permanent teeth, and there is an increased risk of developing osteomyelitis of the jaw. We report here the history of a 9-year-old male with the typical facial and skeletal phenotype of pycnodysostosis but novel oral features. He presented with bilateral progressive facial swelling, which caused functional impairment with chewing and contributed to his severe obstructive sleep apnea (OSA). The severity of his OSA required surgical intervention, and the lesions were resected. Extensive bone remodeling and replacement by fibrous tissue were noted on submucosal dissection, and bilateral subtotal maxillectomies were required. The histopathology of the biopsied lesion was consistent with a giant cell-rich lesion. Genetic testing identified a pathogenic homozygous variant in the gene, c.953G > A, p. (Cys318Tyr). The proband had a good postsurgical response with sustained improvement in his sleep OSA. We present here the history and clinical characteristics of a patient with typical features of pycnodysostosis and an unusual presentation and histopathology of gnathic bone lesions. This report adds to the body of literature on this rare condition and also highlights the finding of giant cell-rich lesions of the gnathic bones. Giant cell-rich lesions in pycnodysostosis have previously been reported in two cases in the literature. While there is not enough evidence to support a certain association with pycnodysostosis, it is prudent to consider regular oral dental reviews in affected individuals to identify pathology early and avoid such life-threatening complications.
PubMed: 37288425
DOI: 10.3389/froh.2023.1188443 -
Contemporary Clinical Dentistry 2017Pycnodysostosis is an uncommon autosomal recessive sclerosing bone disorder which is characterized by short stature and generalized diffuse osteosclerosis. Patients...
Pycnodysostosis is an uncommon autosomal recessive sclerosing bone disorder which is characterized by short stature and generalized diffuse osteosclerosis. Patients usually have a large head with separated sutures, open fontanels, aplasia of frontal sinuses, obtuse mandibular gonial angle, and acroosteolysis of the distal phalanges. This case report showed a 25-year-old female with features pathognomonic of pycnodysostosis. The emphasis is mainly on the early diagnosis as it has an important role in the general health of such patients and prevention of complications.
PubMed: 28566865
DOI: 10.4103/ccd.ccd_1105_16 -
Journal of Pediatric Genetics Mar 2022Here we reported on the genetic findings of a 9-year-old Omani boy with a rare inherited bone disorder. The patient's clinical features include dysmorphic facial...
Here we reported on the genetic findings of a 9-year-old Omani boy with a rare inherited bone disorder. The patient's clinical features include dysmorphic facial features, short stature, and skeletal abnormalities. Exome sequence of the patient's deoxyribonucleic acid revealed a variant in the cathepsin K gene, which was confirmed by Sanger sequencing. These findings established the diagnosis of pycnodysostosis (PKND). To the best of the authors' knowledge, this case is the first case to be reported in the Gulf Cooperative Region of the novel PKND with molecular confirmation.
PubMed: 35186389
DOI: 10.1055/s-0040-1714364