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Contemporary Clinical Dentistry 2020Pycnodysostosis is an autosomal recessive, rare genetic osteosclerotic disorder that caused by mutation in gene coding for Cathepsin K. The bones in pycnodysostosis are...
Pycnodysostosis is an autosomal recessive, rare genetic osteosclerotic disorder that caused by mutation in gene coding for Cathepsin K. The bones in pycnodysostosis are abnormally dense and brittle because of insufficient reabsorption process. This syndrome has a number of characteristic clinical and radiographic signs that differentiate it from other osteosclerotic conditions. This is a rare case report of a male patient with a history of multiple fractures of bones and osteomyelitis of maxilla which is a rare entity.
PubMed: 33850408
DOI: 10.4103/ccd.ccd_382_17 -
Asian Spine Journal Apr 2015Pycnodysostosis is an autosomal recessive disorder characterized by osteosclerosis, small stature, acro-osteolysis of the distal phalanges, loss of the mandibular angle,...
Pycnodysostosis is an autosomal recessive disorder characterized by osteosclerosis, small stature, acro-osteolysis of the distal phalanges, loss of the mandibular angle, separated cranial sutures with open fontanels, and frequent fractures. One identified cause of the disease is reduced activity of the cysteine protease cathepsin K. A 48-year-old woman with a history of frequent fractures presented with a severe gait disturbance. Radiography, computed tomography, magnetic resonance imaging, and gene analysis were performed. Physical examination revealed open fontanels, and radiographs showed increased bone density. DNA sequence analysis revealed a deletion mutation of the cathepsin K gene. We diagnosed pycnodysostosis based on these findings. The magnetic resonance and computed tomography images demonstrated multilevel spinal canal stenosis due to ossification of the yellow ligament. We performed a laminectomy, and the patient's neurological signs and symptoms improved. To our knowledge, this is the first case of pycnodysostosis with ossification of the yellow ligament.
PubMed: 25901243
DOI: 10.4184/asj.2015.9.2.286 -
The FEBS Journal Nov 2018Human cathepsin K (CTSK) is a collagenolytic lysosomal cysteine protease that plays an important role in bone turnover. Mutation in CTSK gene is associated with loss of...
Human cathepsin K (CTSK) is a collagenolytic lysosomal cysteine protease that plays an important role in bone turnover. Mutation in CTSK gene is associated with loss of collagenolytic activity of CTSK leading to an autosomal recessive bone disorder called pycnodysostosis. Although a number of pycnodysostotic missense mutations have been reported, underlying mechanism of the disease is not clear. In this study, we investigated in vitro six recombinant pycnodysostosis-related mutants of human CTSK (G79E, I249T, G243E, G303E, G319C and Q187P). While all the mutants, like wild-type, show similar high levels of expression in Escherichia coli, four of them (G79E, G303E, G319C and Q187P) are inactive, unstable and spontaneously degrade during purification process. In contrast, proteolytic/collagenolytic activity, zymogen activation kinetics and stability of G243E and I249T mutants are nominally affected. Crystal structure of I249T at 1.92 Å resolution shows that the mutation in R-domain causes conformational changes of a surface loop in the L-domain although the catalytic cleft remains unaltered. Molecular simulation, normal mode analysis and fluorescence lifetime measurement eliminated the possibility that the change in L-domain surface loop orientation is a crystallization artefact. CD-based thermal melting profile indicates that stability of I249T is significantly higher than wild-type. Our studies first time reports that pycnodysostosis-related mutations do not always lead to complete loss of general proteolytic activity or specific collagenolytic activity of CTSK. The first crystal structure of a pycnodysostotic mutant (I249T) provides critical information that may pave new avenues towards understanding the disease at molecular level. DATABASE: The atomic co-ordinates and structure factors for I249T mutant of human CTSK (codes 5Z5O) have been deposited in the Protein Data Bank (http://wwpdb.org/).
Topics: Amino Acid Sequence; Catalysis; Cathepsin K; Crystallography, X-Ray; DNA Mutational Analysis; Humans; Models, Molecular; Mutation; Protein Conformation; Pycnodysostosis; Sequence Homology
PubMed: 30199612
DOI: 10.1111/febs.14655 -
Indian Journal of Dentistry Oct 2014Pycnodysostosis, a sclerosing bone dysplasia, is a rare autosomal recessive disorder with an estimated prevalence rate of one in one million. Patients with...
Pycnodysostosis, a sclerosing bone dysplasia, is a rare autosomal recessive disorder with an estimated prevalence rate of one in one million. Patients with pycnodyostosis usually have normal intelligence, sexual development and life span. This condition is characterized by increased bone density and fragility along with oral manifestations like malposition teeth, hypoplastic maxilla, receded chin and delayed eruption of permanent teeth with discharging sinuses in the jaws because of poor blood supply. This is one such rare case report of a 47-year-old patient presenting with a complaint of fractured jaw and reviewing the clinical and radiographic characteristics of pycnodysostosis.
PubMed: 25565757
DOI: 10.4103/0975-962X.144738 -
Revista Brasileira de Ortopedia 2010To discuss what has been described so far in the literature regarding the time taken for fracture consolidation in pycnodysostosis.
OBJECTIVE
To discuss what has been described so far in the literature regarding the time taken for fracture consolidation in pycnodysostosis.
MATERIALS AND METHODS
Thirteen new cases were studied, as available from the medical records and radiographic examinations, thus encompassing a total of 44 fractures in patients evaluated between November 1970 and August 2004 at the Orthopedics Hospital, Goiânia. Field research, simultaneous clinical monitoring for new fractures in two patients and retrospective evaluation of medical records were undertaken. The purpose was to determine the total number of fractures in each patient and to determine which of these were viable for this study. The patient group was composed of three women and two men of mean age 51.4 years. The tibia was the bone most affected, followed by the femur. Fractures for which the follow-up was done at another clinic were excluded.
RESULTS
Out of the 12 fractures that were considered fully suitable for the study, nine occurred in femurs (six in the left femur and three in the right femur); one in the right tibia; one in the right clavicle; and one in the left ulna. Among these 12 fractures, eight developed pseudarthrosis after an average of 29.25 months; three consolidated well after an average of 5.83 months; and one evolved with delayed consolidation in just 2 months.
CONCLUSION
In combination with genetic and micromorphological evaluations, further studies are awaited for reconfirmation of the diagnosis of such a rare clinical entity.
PubMed: 27026972
DOI: 10.1016/S2255-4971(15)30311-6 -
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 -
Medicine Mar 2017Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, craniofacial dysmorphism, acro-osteolysis, osteosclerosis, and brittle...
RATIONALE
Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, craniofacial dysmorphism, acro-osteolysis, osteosclerosis, and brittle bone with poor healing. Pycnodysostosis results from the deficient activity of cathepsin K, a lysosomal cysteine protease that is encoded by CTSK.
PATIENT CONCERNS
We report a Korean adult patient with pycnodysostosis and atypical femur fracture whose diagnosis was confirmed by next-generation sequencing (NGS) of candidate genes. A 41-year-old female patient was presented with a left femur fracture after falling down. Underlying sclerotic bone disease was suspected as a radiographic skeletal survey showed thickened cortical bones, and the total body bone density was increased (T score was 5.3, and Z score was 4.9).
DIAGNOSES
We performed candidate gene sequencing of various sclerotic bone diseases for the differential molecular diagnosis of underlying sclerosing bone disease. Two heterozygous variants of CTSK were detected. One was a frameshift variant in exon 5, c.426delT (p.Phe142Leufs*19), which was previously reported, and the other was a novel missense variant in exon 6, c.755G>A (p.Ser252Asn). Sanger sequencing of CTSK confirmed the 2 heterozygous variants and thus the patient was diagnosed with pycnodysostosis.
INTERVENTIONS
The patient had emergency surgery for subtrochantic femoral fracture.
OUTCOMES
After 4 months of surgery, the patient had almost a full range of hip and knee movements and radiographs show the substantial bridging callus across the fracture.
LESSONS
Candidate gene sequencing could be a useful diagnostic tool for the genetically heterogeneous skeletal dysplasia group, especially in cases with a mild or atypical clinical phenotype.
Topics: Accidental Falls; Adult; Bone and Bones; Cathepsin K; Diagnosis, Differential; Female; Femoral Fractures; Frameshift Mutation; Humans; Mutation, Missense; Pycnodysostosis; Sequence Analysis
PubMed: 28328823
DOI: 10.1097/MD.0000000000006367 -
Iranian Journal of Pediatrics Apr 2014Pycnodysostosis is a rare autosomal recessive osteochondrodysplasia resulting from osteoclast dysfunction. Growth hormone (GH) secretion impairment and low insulin...
OBJECTIVE
Pycnodysostosis is a rare autosomal recessive osteochondrodysplasia resulting from osteoclast dysfunction. Growth hormone (GH) secretion impairment and low insulin growth factor 1 (IGF-I) concentrations have been reported in these patients. The present study aims to describe GH effect on linear growth of eight children with pycnodysostosis.
METHODS
This study was conducted on 8 children suffering from pycnodysostosis. After evaluating systemic diseases, adrenal insufficiency, and hypothyroidism, bone age, height standard deviation score (HtSDS), body mass index (BMI), and some demographical characteristics were measured. To measure the serum GH, we performed two clonidine tests in two different days with an interval of 24 hours. With initiation of the trial, human GH was injected subcutaneously once a day 6 days a week for a period of 1.5 years. The patients were followed up every 3 months to document their height and BMI until 6 months after the end of the treatment.
FINDINGS
All of the patients had growth hormone deficiency. HtSDS at the first visit continued to decrease during the 6 months before starting the treatment; however, HtSDS started to increase after beginning of GH administration. This value again declined after discontinuing the GH. Overall, the mean of linear growth was improved after GH administration in the patients.
CONCLUSION
The present clinical study revealed that GH administration had a positive impact on the linear growth of the children suffering from pycnodysostosis.
PubMed: 25535534
DOI: No ID Found -
Cases Journal Jul 2009Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. The disease has also been named Toulouse-Lautrec syndrome, after the French...
Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. The disease has also been named Toulouse-Lautrec syndrome, after the French artist Henri de Toulouse-Lautrec, who (it has been surmised) suffered from the disease. In 1996, the defective gene responsible for Pycnodysostosis was located, offering accurate diagnosis, carrier testing and a more thorough understanding of this disorder. It is an autosomal recessive osteochondrodysplasia, usually diagnosed at an early age with incidence estimated to be 1.7 per 1 million births. Pycnodysostosis is a lysosomal storage disease of the bone caused by a mutation in the gene that codes the enzyme cathepsin K. The syndrome has been frequently reported in history. This article reports unusual ophthalmologic findings, conductive hearing loss due to suspected otosclerosis and sandal gap deformity in a Pycnodysostosis patient.
PubMed: 19829823
DOI: 10.4076/1757-1626-2-6544 -
Journal of Neurosciences in Rural... Jul 2014Pycnodysostosis is a rare autosomal recessive disorder caused by mutations in the cysteine protease Cathepsin K gene located on chromosome 1q21. It has a well...
Pycnodysostosis is a rare autosomal recessive disorder caused by mutations in the cysteine protease Cathepsin K gene located on chromosome 1q21. It has a well characterized skeletal phenotype which include short stature, generalized increased bone density with propensity of fractures, open calvarial sutures and fontanelle, dental abnormalities, obtuse mandibular angle, resorption of lateral end of clavicle, acro-osteolysis, and in some cases visceromegaly. Central nervous system involvement is very rare and porencephalic cysts has been reported only once, the cause being hypothesised to be an imbalance between the growing brain, its vascular supply and intraventricular fluid pressure. We had a patient with bilateral frontal lobe porencephalic cysts; the patient presenting with complex partial seizures. Cathepsins have been found to be involved in neurological diseases and role of proteases has been well established in gliosis.
PubMed: 25002775
DOI: 10.4103/0976-3147.133606