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Journal of Oral Biology and... 2021Pycnodysostosis is a rare autosomal recessive condition caused by the mutation of CTSK gene. CTSK regulates the activity of Cathepsin K which is responsible for...
Pycnodysostosis is a rare autosomal recessive condition caused by the mutation of CTSK gene. CTSK regulates the activity of Cathepsin K which is responsible for osteoclast-mediated bone resorption. This mutation causes the bones to become dense, sclerotic, brittle, and thus, prone to fracture. Affected individuals have normal cognitive development and life expectancy, however, the quality of life depends on the early diagnosis of the condition. The patient presents with striking clinical (short stature, brachydactyly) and radiological (frontal and parieto-occipital bossing, open sutures, and fontanelles, acro-osteolysis of terminal phalanges) features making the diagnosis clinico-radiographic. In atypical or mild cases with overlapping features, gene mapping is advocated. A plethora of dental anomalies and characteristic craniofacial dysmorphia puts the dentist in a position to diagnose such a case.
PubMed: 34377661
DOI: 10.1016/j.jobcr.2021.07.006 -
Orthopadie (Heidelberg, Germany) Dec 2022Pycnodysostosis is a rare autosomal recessive lysosomal disorder of bone characterized by diffuse skeletal condensation with thickening of the cortex and narrowing of... (Review)
Review
BACKGROUND
Pycnodysostosis is a rare autosomal recessive lysosomal disorder of bone characterized by diffuse skeletal condensation with thickening of the cortex and narrowing of the medullary canal.
CASE PRESENTATION
We present the case of a 4-year-old girl diagnosed with pycnodysostosis and associated pathological tibial fracture. The tibia had an absence of medullary canal. Surgery included reduction and reaming of the canal with placement of a 5 mm diameter telescopic growing nail.
CONCLUSION
The presentation of pycnodysostosis as tibial fracture is rare and there is limited literature on its management. We showed its approach focusing mainly on the management of the absent medullary canal.
Topics: Female; Humans; Child, Preschool; Pycnodysostosis; Tibial Fractures; Tibia; Fractures, Spontaneous
PubMed: 36161513
DOI: 10.1007/s00132-022-04309-7 -
European Journal of Medical Genetics Jul 2021Pycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored...
BACKGROUND
Pycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 25 Indian patients with pycnodysostosis from 20 families.
METHODS
Clinical information was collected on a predesigned clinical proforma. Sanger method was employed to sequence all the exons and exon/intron boundaries of the CTSK gene. Novel variants were systematically assessed by prediction softwares and protein modelling. The pathogenicity of variant was established based on ACMG-AMP criteria. An attempt was also made to establish a genotype-phenotype correlation and devise a diagnostic scoring system based on clinical and radiological findings.
RESULTS
Consanguinity and positive family history were present in 65% (13/20) and 45% (9/20) of the families respectively. Short stature and fractures were the predominant presenting complaints and was evident in 96% (24/25) and 32% (8/25) of affected individuals respectively. Gestalt facial phenotype and acro-osteolysis were present in 76% (19/25) and 82.6% (19/23) of the individuals respectively. Hepatosplenomegaly was present in 15% (3/20) of the individuals with one of them having severe anaemia. Causative sequence variations were identified in all of them. A total of 19 variants were identified from 20 families amongst which 10 were novel. Homozygous variants were identified in 90% (18/20) families. Amongst the novel variants, there was a considerable proportion (40%) of frameshift variants (4/10). No significant genotype-phenotype correlation was noted. Scoring based on clinical and radiological findings led to the proposal that a minimum of 2 scores in each category is required in addition to high bone density to diagnose pycnodysostosis with certainty.
CONCLUSION
This study delineated the genotypic and phenotypic characterisation of Indian patients with pycnodysostosis with identification of 10 novel variants. We also attempted to develop a clinically useful diagnostic scoring system which requires further validation.
Topics: Cathepsin K; Child; Cohort Studies; Female; Gene Frequency; Homozygote; Humans; Male; Mutation; Phenotype; Pycnodysostosis
PubMed: 33945887
DOI: 10.1016/j.ejmg.2021.104235 -
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 -
Indian Journal of Orthopaedics Aug 2022Atypical subtrochanteric femoral fractures are a common problem associated with pycnodysostosis. Pycnodysostosis is a rare sclerotic bone disease caused by a mutation in...
ABSTRACT
Atypical subtrochanteric femoral fractures are a common problem associated with pycnodysostosis. Pycnodysostosis is a rare sclerotic bone disease caused by a mutation in the cathepsin K gene. Fracture healing in pycnodysostosis cases is typically inferior. Here, we report a case of bilateral atypical subtrochanteric femoral fractures in one patient with pycnodysostosis. The right subtrochanteric fracture was treated with open reduction and internal fixation (open plating), and united through primary bone healing, while the left one was treated with closed reduction and internal fixation (submuscular plating), and united through secondary bone healing. Although the time to bony union was delayed, fracture union after extramedullary osteosynthesis was obtained in both atypical fractures, demonstrating that both primary and secondary bone healing is possible in patients with pycnodysostosis.
LEVEL OF CLINICAL EVIDENCE
4.
PubMed: 35928669
DOI: 10.1007/s43465-022-00675-8 -
American Journal of Medical Genetics.... Aug 2021Pycnodysostosis is characterized by short stature, osteosclerosis, acro-osteolysis, increased tendency of fractures, and distinctive dysmorphic features. It is a rare...
Pycnodysostosis is characterized by short stature, osteosclerosis, acro-osteolysis, increased tendency of fractures, and distinctive dysmorphic features. It is a rare autosomal recessive disease caused by biallelic CTSK mutations. The clinical details of 18 patients from Saudi Arabia were reviewed. Short stature, osteopetrosis, acro-osteolysis, and distinctive facial dysmorphism were documented in all cases. Our results highlight the significant complications associated with this disease. The large anterior fontanelle is one of the cardinal signs of this disease; however, half of our patients had small fontanelles and a quarter had craniosynostosis, which caused optic nerve compression. Sleep apnea was of the major complications in three patients. Bone fracture can be a presenting symptom, and in our patients it mainly occurred after the age of 3 years. Bone marrow suppression was seen in a single patient of our cohort who was misdiagnosed initially with malignant osteopetrosis. In this study, we also describe two novel (c.5G > A [p.Trp2Ter], c.538G > A [p.Gly180Ser]) and two reported (c.244-29 A > G, c.830C > T [p.Ala277Val]) CTSK mutations. Our results indicate that the recurrent intronic variant, c.244-29 A > G is likely to be a founder mutation, as it was found in 78% (14/18 patients) of our cohort belonging to the same tribe.
Topics: Alleles; Cathepsin K; Child, Preschool; Consanguinity; Facies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Imaging, Three-Dimensional; Male; Mutation; Pedigree; Phenotype; Pycnodysostosis; Radiography; Saudi Arabia; Tomography, X-Ray Computed
PubMed: 33963797
DOI: 10.1002/ajmg.a.62230 -
BMJ Case Reports Sep 2023Pycnodysostosis is a rare genetic condition that leads to generalised bony sclerosis and increased fracture risk. Orthopaedic specialists play a crucial role in managing...
Pycnodysostosis is a rare genetic condition that leads to generalised bony sclerosis and increased fracture risk. Orthopaedic specialists play a crucial role in managing affected children due to their susceptibility to frequent fractures. We had a case of a middle childhood female patient with pycnodysostosis and a femur fracture. Initially, an attempt using the Titanium Elastic Nailing System was made, but the sclerotic metaphyseal bone made it challenging. So, we opted for a 4.5 mm locked compressive plate, with multiple drill bits as a backup due to potential drill breakage. Though elastic nailing is preferred for paediatric long bone fractures, surgeons must be prepared for extremely sclerotic cortices and a narrow medullary canal when dealing with patients with pycnodysostosis. Open fixation and multiple drill bits in the toolkit are essential to overcome the potential obstacles during the procedure.
Topics: Humans; Child; Female; Pycnodysostosis; Femoral Fractures; Patients; Adrenal Medulla; Bone Plates; Rare Diseases
PubMed: 37723084
DOI: 10.1136/bcr-2022-252667 -
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 -
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 -
Journal of Clinical Medicine Apr 2024: Pycnodysostosis is a rare genetic disorder causing skeletal dysplasia. It is determined by a gene mutation leading to cathepsin K deficiency and predisposes a patient...
: Pycnodysostosis is a rare genetic disorder causing skeletal dysplasia. It is determined by a gene mutation leading to cathepsin K deficiency and predisposes a patient to osteosclerosis, resulting in increased bone fragility. The altered bone quality typical of this disease is responsible for an increased risk of fractures. The purpose of our study was to evaluate the orthopedic manifestations and potential pitfalls in the surgical treatments of pathological fractures in a series of patients treated in our institution who were affected by pycnodysostosis. : We retrospectively evaluated clinical and radiographic characteristics of five patients with pycnodysostosis treated for pathological fractures at our hospital in the past 5 years. : Two male and three female patients were included in this study. Four patients had a family history of pycnodysostosis. All the patients were of short stature, but only two underwent growth hormone treatment. All the patients experienced fractures, mostly in their lower limbs and occurring as a result of low-energy trauma. Most of the patients experienced either consolidation delay or nonunion. : The orthopedic management of fractures in patients with pycnodysostosis poses an ongoing challenge for orthopedic surgeons. The fact that the bone is simultaneously sclerotic and brittle makes any orthopedic surgical treatment challenging and at a high risk of nonunion in any case.
PubMed: 38731051
DOI: 10.3390/jcm13092522