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Cureus Apr 2022Pycnodysostosis (PYCD) is an autosomal recessive lysosomal storage disorder of the bone which leads to stereotypical abnormalities consisting of, but not limited to,... (Review)
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. Elig-ibility 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.
PubMed: 35602818
DOI: 10.7759/cureus.24275 -
The Pan African Medical Journal 2018Pycnodysostosis is a very rare genetic disease of the bone characterized by osteocondensation associated with dysmorphic syndrome and growth retardation. This study aims...
Pycnodysostosis is a very rare genetic disease of the bone characterized by osteocondensation associated with dysmorphic syndrome and growth retardation. This study aims to highlight the phenotypic abnormalities, the radiological signs, the therapeutic and evolutionary features of pycnodysostosis in a 11-year old child. The child was referred by his dentist for clinical evaluation. He was born to first-degree consanguineous parents and had recurrent spontaneous fractures since the age of 3 years. Clinical examination showed dysmorphic syndrome characterized by frontal hump, persistent anterior fontanelle, micrognathia, finger deformities, dental malposition, curved nails, asymmetric chest, lumbar spine scoliosis with severe growth retardation (-4DS). Skeletal X-rays showed bony densification of the skull base, persistent anterior fontanelle, dental malposition, diaphysometaphyseal densification of the long bones mainly at the level of the lower limbs with malunions and tapered phalanges of the hands. Bone densitometry was normal. The diagnosis of pycnodysostosis was retained based on the clinical and radiological signs. Genetic counselling was proposed to the family as well as dental and orthopaedic treatment. Pycnodysostosis is a rare disorder; diagnosis is sometimes difficult and delayed posing diagnostic problem due to its resemblance with osteoporosis. Treatment is essentially based on fractures and dental caries prevention.
Topics: Abnormalities, Multiple; Child; Fractures, Spontaneous; Humans; Male; Pycnodysostosis
PubMed: 31011394
DOI: 10.11604/pamj.2018.31.93.8388 -
Molecular Endocrinology (Baltimore, Md.) Feb 2015Osteoclasts are bone-resorbing cells essential for skeletal remodeling and regeneration. However, excessive osteoclasts often contribute to prevalent bone degenerative... (Review)
Review
Osteoclasts are bone-resorbing cells essential for skeletal remodeling and regeneration. However, excessive osteoclasts often contribute to prevalent bone degenerative diseases such as osteoporosis, arthritis, and cancer bone metastasis. Osteoclast dysregulation is also associated with rare disorders such as osteopetrosis, pycnodysostosis, Paget's disease, and Gorham-Stout syndrome. The nuclear receptor (NR) family of transcription factors functions as metabolic sensors that control a variety of physiological processes including skeletal homeostasis and serves as attractive therapeutic targets for many diseases. In this review, we highlight recent findings on the new players and the new mechanisms for how NRs regulate osteoclast differentiation and bone resorption. An enhanced understanding of NR functions in osteoclastogenesis will facilitate the development of not only novel osteoprotective medicine but also prudent strategies to minimize the adverse skeletal effects of certain NR-targeting drugs for a better treatment of cancer and metabolic diseases.
Topics: Animals; Bone Remodeling; Humans; Osteoclasts; Receptors, Cytoplasmic and Nuclear
PubMed: 25549044
DOI: 10.1210/me.2014-1316 -
International Journal of Molecular... Nov 2022Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in... (Review)
Review
Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.
Topics: Cathepsin K; Collagen Type I; Bone and Bones; Cysteine Proteases
PubMed: 36430239
DOI: 10.3390/ijms232213762 -
European Annals of Otorhinolaryngology,... Apr 2016Pycnodysostosis is a rare genetic disorder caused by a mutation of the cathepsin K gene involved in bone turnover. It is responsible, in particular, for a combination of... (Review)
Review
OBJECTIVES
Pycnodysostosis is a rare genetic disorder caused by a mutation of the cathepsin K gene involved in bone turnover. It is responsible, in particular, for a combination of dwarfism and bone fragility. Upper airway obstruction may be observed, but associated stridor has never been previously described.
MATERIALS AND METHODS
Single-centre retrospective study over a period of 15 years with review of the literature.
RESULTS
Three children (aged 2-18 months) were managed for stridor and obstructive sleep apnoea syndrome confirmed by polysomnography. Physical examination of these children revealed stridor with laryngomalacia, characteristic dysmorphic features and failure to thrive. Patient 1 presented typical laryngomalacia treated by surgical section of the aryepiglottic folds. Patient 2 presented upper airway obstruction with a narrow nasopharynx and long soft palate, treated by surgery and noninvasive ventilation. Patient 3 presented moderate laryngomalacia and nasal obstruction, treated by surgery and noninvasive ventilation.
CONCLUSION
The diagnosis of pycnodysostosis must be considered in the presence of atypical laryngomalacia associated with multifactorial upper airway obstruction, failure to thrive and dysmorphic syndrome. A genetics consultation is essential in these patients.
Topics: Humans; Infant; Male; Pycnodysostosis; Respiratory Sounds; Retrospective Studies
PubMed: 26856677
DOI: 10.1016/j.anorl.2015.06.005 -
Endocrine Jun 2016During the past 15 years there has been an expansion of our knowledge of the cellular and molecular mechanisms regulating bone remodeling that identified new signaling... (Review)
Review
During the past 15 years there has been an expansion of our knowledge of the cellular and molecular mechanisms regulating bone remodeling that identified new signaling pathways fundamental for bone renewal as well as previously unknown interactions between bone cells. Central for these developments have been studies of rare bone disorders. These findings, in turn, have led to new treatment paradigms for osteoporosis some of which are at late stages of clinical development. In this article, we review three rare skeletal disorders with case descriptions, pycnodysostosis and the craniotubular hyperostoses sclerosteosis and van Buchem disease that led to the development of cathepsin K and sclerostin inhibitors, respectively, for the treatment of osteoporosis.
Topics: Bone Diseases; Bone Remodeling; Drug Discovery; Humans; Hyperostosis; Osteochondrodysplasias; Osteoporosis; Rare Diseases; Syndactyly
PubMed: 26892377
DOI: 10.1007/s12020-016-0888-7 -
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 -
Genes Sep 2021Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization...
Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization of Egyptian patients, with emphasis on identifying unusual phenotypes and raising awareness about pycnodysostosis with different presentations to avoid a mis- or under-diagnosis and consequent mismanagement. We report on 22 Egyptian pycnodysostosis patients, including 9 new participants, all descending from consanguineous families and their ages ranging from 6 to 15 years. In addition, prenatal diagnosis was performed in one family with affected siblings. They all presented with short stature, except for one patient who presented with pancytopenia as her primary complaint. Moreover, 41.2% of patients had sleep apnea, 14% presented with craniosynostosis, and 44.4% had failure of tooth development. Molecular analysis via direct exome sequencing of the cathepsin K gene revealed three novel mutations ((NM_000396.3) c.761_763delCCT, c.864_865delAA, and c.509G>T) as well as two previously reported mutations among nine new cases. The following is our conclusion: This study expands the molecular spectrum of pycnodysostosis by identifying three novel mutations and adds to the clinical and orodental aspects of the disease. The link between the gene mutations and the failure of tooth development has not been established, and further studies could help to improve our understanding of the molecular pathology.
Topics: Adolescent; Cathepsin K; Cells, Cultured; Child; Female; Humans; Male; Mutation; Phenotype; Protein Conformation; Pycnodysostosis; Tooth
PubMed: 34680947
DOI: 10.3390/genes12101552 -
International Journal of Molecular... Feb 2021Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of... (Clinical Trial)
Clinical Trial
Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.
Topics: Adult; Bone Resorption; Cathepsin K; Cathepsin L; Cathepsins; Female; Humans; Lactation; Osteoclasts; Pycnodysostosis
PubMed: 33670411
DOI: 10.3390/ijms22041810