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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 -
Orphanet Journal of Rare Diseases Apr 2014To characterize cathepsin K (CTSK) mutations in a group of patients with pycnodysostosis, who presented with either short stature or atypical fractures to pediatric...
BACKGROUND
To characterize cathepsin K (CTSK) mutations in a group of patients with pycnodysostosis, who presented with either short stature or atypical fractures to pediatric endocrinology or dysmorphic features to pediatric genetics clinics.
METHODS
Seven exons and exon/intron boundaries of CTSK gene for the children and their families were amplified with PCR and sequenced. Sixteen patients from 14 families with pycnodysostosis, presenting with typical dysmorphic features, short stature, frequent fractures and osteosclerosis, were included in the study.
RESULTS
We identified five missense mutations (M1I, I249T, L7P, D80Y and D169N), one nonsense mutation (R312X) and one 301 bp insertion in intron 7, which is revealed as Alu sequence; among them, only L7P and I249 were described previously. The mutations were homozygous in all cases, and the families mostly originated from the region where consanguineous marriage rate is the highest. Patients with M1I mutation had fractures, at younger ages than the other pycnodysostosis cases in our cohort which were most probably related to the severity of mutation, since M1I initiates the translation, and mutation might lead to the complete absence of the protein. The typical finding of pycnodysostosis, acroosteolysis, could not be detected in two patients, although other patients carrying the same mutations had acroosteolysis. Additionally, none of the previously described hot spot mutations were seen in our cohort; indeed, L7P and R312X were the most frequently detected mutations.
CONCLUSIONS
We described a large cohort of pycnodysostosis patients with genetic and phenotypic features, and, first Alu sequence insertion in pycnodysostosis.
Topics: Cathepsin K; Cohort Studies; Exons; Female; Genotype; Humans; Introns; Male; Mutation, Missense; Pedigree; Phenotype; Polymerase Chain Reaction; Pycnodysostosis
PubMed: 24767306
DOI: 10.1186/1750-1172-9-60 -
Medicina Oral, Patologia Oral Y Cirugia... Oct 2008Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. It is a genetic disorder, usually diagnosed at an early age. However, the... (Review)
Review
Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. It is a genetic disorder, usually diagnosed at an early age. However, the diagnosis is sometimes late, made as a result of bone fracture, given the severe bone fragility resulting from increased bone density. Oral and maxillofacial manifestations of this disease are very clear. The head is usually large, the nose beaked, the mandibular angle obtuse, and both maxilla and mandible hypoplastic. Dental abnormalities and impaction are observed, as well as alterations in eruption and frequent dental crowding. The differential diagnosis is established with osteopetrosis, cleidocranial dysplasia and idiopathic acro-osteolysis. This article reviews the clinical and radiographic characteristics of pycnodysostosis based on three clinical cases of patients with this disease.
Topics: Abnormalities, Multiple; Adult; Bone and Bones; Dwarfism; Female; Humans; Jaw Abnormalities; Male; Middle Aged
PubMed: 18830170
DOI: No ID Found -
Journal of Medical Genetics Dec 1989We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular...
We describe a case of pycnodysostosis with porencephaly and suggest an explanation for the porencephaly by a mechanism of imbalance between brain growth and its vascular supply and a normal but unopposed cerebrospinal fluid pressure.
Topics: Adult; Brain Diseases; Cysts; Diagnosis, Differential; Facial Expression; Humans; Male; Osteosclerosis; Syndrome
PubMed: 2614800
DOI: 10.1136/jmg.26.12.782 -
Journal of Clinical and Experimental... Oct 2017Pycnodysostosis is a rare disorder that was first described in 1962; however, it was only in 1996 that the defective gene was discovered, which led to a better...
Pycnodysostosis is a rare disorder that was first described in 1962; however, it was only in 1996 that the defective gene was discovered, which led to a better understanding of this disease. This study reports and discuss a case of pycnodysostosis. In addition, a search of articles published in PubMed-Medline was performed. The case was a 13-year-old girl who was referred to a private clinic for dental treatment. Clinical examination showed midface hypoplasia, prominent cheeks, a high nasal bridge, beaked nose, spoon-shaped fingers, frontal bossing, open fontanelles and dental alterations, findings compatible with pycnodysostosis. Patients with this disease also suffer from fractures because of bone hardness with almost no elasticity, a fact that requires special care particularly in the case of children and adolescents. The diagnosis of pycnodysostosis is made based on clinical and radiographic findings. Clinicians should be aware of this disorder to provide adequate dental treatment. Pycnodysostosis, developmental bone disease, imaging diagnosis.
PubMed: 29167721
DOI: 10.4317/jced.54105 -
Theranostics 2019Human encodes voltage-gated chloride channel 7 (ClC-7); mutations of lead to osteopetrosis which is characterized by increased bone mass and impaired osteoclast...
Human encodes voltage-gated chloride channel 7 (ClC-7); mutations of lead to osteopetrosis which is characterized by increased bone mass and impaired osteoclast function. In our previous clinical practice, we noticed that osteopetrosis patients with mutations had some special deformities in craniofacial morphology and tooth dysplasia. It is unclear whether these phenotypes are the typical features of involved osteopetrosis and whether ClC-7 could regulate the development of craniofacial bone and tooth in some signaling pathways. : First, we collected 80 osteopetrosis cases from the literature and compared their craniofacial and dental phenotypes. Second, four osteopetrosis pedigrees with mutations were recruited from our clinic for gene testing and clinical analysis of their craniofacial and dental phenotypes. Third, we used a zebrafish model with morpholino treatment to detect the effects of ClC-7 deficiency on the development of craniofacial and dental phenotypes. General observation, whole mount alcian blue and alizarin red staining, whole mount hybridization, scanning electron microscope observation, lysoSensor staining, Q-PCR and western blotting were performed to observe the characteristics of craniofacial bone and tooth changes. Fourth, mouse marrow stromal cells were further primarily cultured to detect ClC-7 related mRNA and protein changes using siRNA, Q-PCR and western blotting. Over 84% of osteopetrosis patients in the literature had some typical craniofacial and tooth phenotypes, including macrocephaly, frontal bossing, and changes in shape and proportions of facial skeleton, and these unique features are more severe and frequent in autosomal recessive osteopetrosis than in autosomal dominant osteopetrosis patients. Our four pedigrees with mutations confirmed the aforementioned clinical features. knockdown in zebrafish reproduced the craniofacial cartilage defects and various dental malformations combined the decreased levels of , , , , and . Loss of function resulted in lysosomal storage in the brain and jaw as well as downregulated cathepsin K (CTSK). The craniofacial phenotype severity also presented a dose-dependent relationship with the levels of ClC-7 and CTSK. ClC-7/CTSK further altered the balance of TGF-β/BMP signaling pathway, causing elevated TGF-β-like Smad2 signals and reduced BMP-like Smad1/5/8 signals in morphants. SB431542 inhibitor of TGF-β pathway partially rescued the aforementioned craniofacial bone and tooth defects of morphants. The ClC-7 involved CTSK/BMP and SMAD changes were also confirmed in mouse bone marrow stromal cells. These findings highlighted the vital role of in zebrafish craniofacial bone and tooth development and mineralization, revealing novel insights for the causation of osteopetrosis with mutations. The mechanism chain of ClC-7/CTSK/ TGF-β/BMP/SMAD might explain the typical craniofacial bone and tooth changes in osteopetrosis as well as pycnodysostosis patients.
Topics: Animals; Chloride Channels; Disease Models, Animal; Facial Bones; Humans; Mice; Models, Theoretical; Mutant Proteins; Osteopetrosis; Skull; Tooth; Zebrafish
PubMed: 30867839
DOI: 10.7150/thno.29761 -
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 -
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 -
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 -
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