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Brazilian Journal of Otorhinolaryngology 2021Pycnodysostosis is a rare autosomal recessive syndrome that provides the abnormal bone metabolism that increases the susceptibility of patients to develop osteomyelitis. (Review)
Review
INTRODUCTION
Pycnodysostosis is a rare autosomal recessive syndrome that provides the abnormal bone metabolism that increases the susceptibility of patients to develop osteomyelitis.
OBJECTIVE
This systematic review was conducted to analyze the risk factors associated with the development of complications in the jaws (fractures and osteomyelitis), as well as their clinical-pathological characteristics and therapeutic approaches in patients with pycnodysostosis.
METHODS
Searches were performed in the PubMed, Web of Science, Scopus, Lilacs, and Cochrane databases. Case reports or case series that met the eligibility criteria according to the PRISMA statement were included. The full texts of 31 articles were retrieved. Twenty of these articles published between 1969 and 2018 were selected, which described 26 cases of osteomyelitis in patients with pycnodysostosis.
RESULTS
The mean age of the patients was 37.84 years; the male-to-female was 1.36:1. The mandible was the most affected site (76.9%). Tooth extraction was the main risk factor for osteomyelitis (61.5%), followed by infection (26.8%) and mandibular fracture (23.0%). Antibiotic therapy alone or combined with some surgical procedure was the treatment used in most cases (80.7%).
CONCLUSION
The findings of this review showed that patients with pycnodysostosis are more likely to develop osteomyelitis of the jaws after surgical procedures, especially tooth extraction which remains the main risk factor for its establishment. In addition, prophylactic antibiotic-therapy in the pre- and postoperative periods may prevent the development of osteomyelitis in pycnodysostosis.
Topics: Adult; Female; Humans; Male; Mandible; Osteomyelitis; Pycnodysostosis
PubMed: 33579598
DOI: 10.1016/j.bjorl.2020.12.009 -
European Journal of Medical Genetics Feb 2021Pycnodysostosis is a rare autosomal recessive osteosclerotic skeletal dysplasia caused by variants in the cathepsin K gene (CTSK). Clinical features include short...
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.
Topics: Adult; Bone Density; Cathepsin K; Child; Female; Growth Hormone; Humans; Male; Middle Aged; Mutation; Phenotype; Pycnodysostosis; Quality of Life
PubMed: 33429075
DOI: 10.1016/j.ejmg.2021.104135 -
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 -
Strategies in Trauma and Limb... 2019We present details of a surgical technique to create an intramedullary canal to allow intramedullary fracture fixation in patients with osteopetrosis. Clinical cases are...
AIM
We present details of a surgical technique to create an intramedullary canal to allow intramedullary fracture fixation in patients with osteopetrosis. Clinical cases are used to facilitate the description.
BACKGROUND
Osteopetrosis is a rare, hereditary condition characterised by hard, brittle, "marble bone;" primarily due to osteoclast dysfunction. Patients are prone to fractures and subsequently nonunions, periprosthetic fractures, and metal-ware failure are commonly seen. Due to the increased bone density, deformity, and obliteration of the medullary cavity, fracture fixation is also technically demanding.
TECHNIQUE
Creation of a medullary canal allows the use of intramedullary fixation rather than plate and screws for long-bone fractures.
KEY FACTORS
A new sharp drill bit should be used for each case as blunt drills are more likely to break.Bone is drilled in a pulsatile fashion, with withdrawal every 2-4 seconds for bone swarf to be removed.Constant cooling of the drill bit with saline to help prevent bone necrosis and drill breakage.Regular exchanging of drill bit sizes to expand the canal. The smaller drills start the canal and are used to direct progress. Sequential expansion during canal creation is preferred.Regular use of orthogonal radiographs to ensure correct canal positioning and prevent perforation.
CONCLUSION
The creation of an intramedullary canal allows intramedullary fracture fixation. In our experience, this technique gives the orthopaedic surgeon a safe and effective method for treating long-bone fractures in patients with osteopetrosis.
CLINICAL RELEVANCE
Fractures and nonunions in patients with osteopetrosis are difficult to manage; and by detailing this technique, a further option is now available for surgeons when deciding upon fixation method.
HOW TO CITE THIS ARTICLE
Kent J, Ferguson D. Intramedullary Canal-creation Technique for Patients with Osteopetrosis. Strategies Trauma Limb Reconstr 2019;14(3):155-162.
PubMed: 32742432
DOI: 10.5005/jp-journals-10080-1424 -
Clinical, Cosmetic and Investigational... 2020Pycnodysostosis (PYCD) is a rare autosomal recessive skeletal dysplasia arising from a change in the production of the cathepsin K enzyme and it is also known as...
Pycnodysostosis (PYCD) is a rare autosomal recessive skeletal dysplasia arising from a change in the production of the cathepsin K enzyme and it is also known as Maroteaux-Lamy Syndrome. The main changes in the buccal and maxillofacial region are modifications of the facial bones (leading to the loss of the mandibular angle due to micrognathia), deep palate, premature and/or delayed tooth eruption, hypopneumatization of the maxillary sinuses, chin hypoplasia, hypercementosis, enamel hypoplasia, hyperdontia, incomplete dentin calcification, root hypoplasia, pulp chamber obliteration, and increased free functional space. This paper aims to report a case of a patient with PYCD, in which are highlighted the oral manifestations of this syndrome and present an option of oral rehabilitative treatment through a removable overdenture made on natural tooth of the patient. The technique of dental coating through overdenture is a simple, viable and conservative alternative for oral rehabilitation of patients with large maxillomandibular discrepancies, as in cases of pycnodysostosis, especially in the presence of increased free space - characteristic of patients with this syndrome. The result was quite satisfactory both aesthetically and functionally and provided a better life quality for the patient.
PubMed: 32346314
DOI: 10.2147/CCIDE.S247614 -
Journal of Clinical Research in... Nov 2020Pycnodysostosis is a rare autosomal recessive osteosclerotic bone disorder associated with short stature and multiple bony abnormalities. Growth hormone (GH) deficiency...
Pycnodysostosis is a rare autosomal recessive osteosclerotic bone disorder associated with short stature and multiple bony abnormalities. Growth hormone (GH) deficiency may contribute to short stature in about 50% of patients. Available literature has rarely reported other pituitary hormone deficiencies in pyknodysostosis. Though the management remains conservative, recombinant human GH (rhGH) has been tried in selected patients. Here we present a case of pycnodysostosis which was evaluated for associated co-morbidities and found to have multiple pituitary hormone deficiencies. A 7-year-old girl was referred to our centre for evaluation of short stature. On examination, she had frontal and occipital bossing, limited mouth opening, hyperdontia with multiple carries, short and stubby digits and short stature. Investigation revealed dense sclerotic bones with frontal and occipital bossing, non-fusion of sutures with obtuse mandibular angle, non-pneumatised sinuses, small ‘J’ shaped sella turcica, acro-osteolysis of digits and absent medullary cavities. gene mutation analysis confirmed the diagnosis of pycnodysostosis. She was screened for associated co-morbidities and was found to have concomitant GH deficiency. Treatment with rhGH brought about an increase of 1 standard deviation score in height over 2 years and also unmasked central hypothyroidism at three months necessitating thyroxine replacement.
Topics: Abnormalities, Multiple; Child; Facies; Female; Human Growth Hormone; Humans; Hypothyroidism; Pituitary Hormones; Pituitary Hormones, Anterior; Prognosis; Pycnodysostosis; Thyroxine; Transcription Factor Pit-1
PubMed: 32248673
DOI: 10.4274/jcrpe.galenos.2020.2019.0194 -
The Pan African Medical Journal 2020
PubMed: 32117521
DOI: 10.11604/pamj.2020.35.5.8581 -
Blood Feb 2020
Topics: Heinz Bodies; Humans; Infant, Newborn; Pycnodysostosis
PubMed: 32106309
DOI: 10.1182/blood.2019004019 -
Journal of Clinical Orthopaedics and... 2020Pycnodysostosis is a rare inherited disorder of autosomal recessive trait causing cathepsin K deficiency, leading to failure of osteoclastic activity. Brittle and...
Pycnodysostosis is a rare inherited disorder of autosomal recessive trait causing cathepsin K deficiency, leading to failure of osteoclastic activity. Brittle and sclerotic bones which are prone for frequent fractures is the characteristic feature of this congenital disorder. Despite good healing potential there are few issues in the management of fractures in pycnodysostosis patients. In this article we report the challenges faced in managing a fracture of the femoral shaft in a 12 year old girl with pycnodysostosis. For early rehabilitation and to avoid deformity and shortening, we opted for surgical fixation over conservative treatment. Narrow medullary canal ruled out the option for titanium elastic nail fixation. 4.5mm dynamic compression plate was used to fix the fracture. Sclerotic bone made drilling extremely difficult. Deformed femoral shaft allowed plating over the anterior surface only, instead of the routine lateral surface plating. Postoperative fracture healing was satisfactory. Implant was removed after 18 months.
PubMed: 32099307
DOI: 10.1016/j.jcot.2018.09.012 -
Whole-exome sequencing identified a novel variant in an Iranian patient affected by pycnodysostosis.Molecular Genetics & Genomic Medicine Mar 2020Whole-exome sequencing (WES) has emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. In this study, we aimed to find the potential...
BACKGROUND
Whole-exome sequencing (WES) has emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. In this study, we aimed to find the potential genetic cause of skeletal disease, a heterogeneous disease, revealing the obvious short stature phenotype. In an Iranian family, we used solo-WES in a suspected patient to decipher the potential genetic cause(s).
METHODS
A comprehensive clinical and genotyping examination was applied to suspect the disease of the patient. The solo clinical WES was exploited, and the derived data were filtered according to the standard pipelines. In order to validate the WES finding, the region harboring the candidate variant in the CTSK gene was amplified from genomic DNA and sequenced directly by Sanger sequencing.
RESULTS
Sequence analysis revealed a rare novel nonsense variant, p.(Trp320*); c.905G>A, in the CTSK gene (NM_000396.3). In silico analysis shed light on the contribution of the variant to the pathogenicity of pycnodysostosis. This variant was confirmed by Sanger sequencing and further clinical examinations of the patient confirmed the disease.
CONCLUSION
The present study shows a rare variant of the CTSK gene, which inherited as autosomal recessive, in an Iranian male patient with pycnodysostosis. Taken together, the novel nonsense CTSK variant meets the criteria of being likely pathogenic according to the American College of Medical Genetics and Genomics-the Association for Molecular Pathology (ACMG-AMP) variant interpretation guidelines.
Topics: Adolescent; Cathepsin K; Codon, Nonsense; Genetic Testing; Humans; Male; Pycnodysostosis; Exome Sequencing
PubMed: 31944631
DOI: 10.1002/mgg3.1118