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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 -
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 -
Archives of Disease in Childhood Dec 1963
Topics: Bone and Bones; Child; Congenital Abnormalities; Fingers; Genetics, Medical; Humans; Osteopetrosis; Pycnodysostosis; Skull; Tooth
PubMed: 14092063
DOI: 10.1136/adc.38.202.620 -
Proceedings of the Royal Society of... Sep 1963
PubMed: 19994286
DOI: No ID Found -
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 -
Imaging Science in Dentistry Mar 2024Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial... (Review)
Review
PURPOSE
Pycnodysostosis (PYCD), an autosomal recessive syndrome, is characterized by an imbalance in bone remodeling that produces various clinical and radiographic craniofacial manifestations. This review represents a systematic examination of these manifestations, as well as oral features associated with PYCD.
MATERIALS AND METHODS
A systematic review was conducted across 8 databases from February to March 2023. The search strategy focused on studies reporting cases of PYCD that examined the clinical and radiographic craniofacial and oral characteristics associated with this syndrome.
RESULTS
The review included 84 studies, encompassing a total of 179 cases of PYCD. More than half of the patients were female (55.3%), and the mean age was 14.7 years. Parental consanguinity was reported in 51.4% of the cases. The most common craniofacial clinical manifestation was a prominent nose, observed in 57.5% of cases. Radiographically, the most frequently reported craniofacial characteristics included the presence of an obtuse mandibular angle (84.3%) and frontal cranial bosses (82.1%). Clinical and radiographic examinations revealed oral alterations, with micrognathia present in 62.6% of patients and malocclusion in 59.2%. Among dental anomalies, tooth agenesis was the most commonly reported, affecting 15.6% of patients.
CONCLUSION
Understanding the clinical and radiographic craniofacial features of PYCD is crucial for dental professionals. This knowledge enables these clinicians to devise effective treatment plans and improve patient quality of life.
PubMed: 38571780
DOI: 10.5624/isd.20230191 -
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 -
Case Reports in Genetics 2021Osteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature,...
Osteopetrosis is a disorder characterized by high bone density, hepatosplenomegaly, visual and hearing loss, and anemia. Pycnodysostosis presents with short stature, acroosteolysis, and dense bones. We, hereby, present here a family with autosomal dominant osteopetrosis and also children with recessive osteopetrosis and pycnodysostosis. The molecular confirmation was done in 3 cases. Genetic heterogeneity in clinical presentation is discussed here. Further studies will help in identifying epigenetic alterations and population-specific variants and also developing targeted therapies.
PubMed: 34777883
DOI: 10.1155/2021/7133508 -
Molecular Genetics & Genomic Medicine May 2022Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific...
BACKGROUND
Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Radiographic features include acro-osteolysis of the distal phalanges in association with sclerosing bone lesions with multiple fractures. The polymorphism of the clinical manifestations of pycnodysostosis and low prevalence of the disorder lead to the difficulties with early.
METHODS
The following tests were used for diagnostics: genealogical analysis, clinical examination, neurological examination according to the standard method with an assessment of the psychoemotional sphere, radiological analysis, searching for pathogenic variants in the CTSK gene by the automated Sanger sequencing.
RESULTS
We describe first clinical and genetic characteristics of three Russian patients with pycnodysostosis from unrelated families. Two patients have a novel homozygous nucleotide substitution c.746T>A (p. Ile249Asn), and one has a previously described homozygous pathogenic variant c.746T>C (p.Ile249Thr) in the CTSK gene. In all three cases, a transition or transversion was found at nucleotide position 746 in exon 6 of the CTSK gene, leading to two different amino acid substitutions in the polypeptide chain. The obtained results may indicate the presence of a major pathogenic variant in the CTSK gene, leading to the typical manifestation of the disease.
CONCLUSION
The data presented in the study enlarge the clinical, radiological, and mutational spectrum of pycnodysostosis. Typical clinical manifestations and the small size of the CTSK gene make the automated Sanger sequencing the optimal method for diagnosis of pycnodysostosis.
Topics: Cathepsin K; Homozygote; Humans; Mutation; Nucleotides; Pycnodysostosis
PubMed: 35315254
DOI: 10.1002/mgg3.1904 -
Journal of Ayub Medical College,... 2022Pycnodysostosis is a rare disease with very few reported cased all over the world. It was first described in 1963 by Maroteaux and Lamy. It is also known as...
Pycnodysostosis is a rare disease with very few reported cased all over the world. It was first described in 1963 by Maroteaux and Lamy. It is also known as Toulouse-Lautrec syndrome, after a French artist, Henri de Toulouse Lautrec. The affected gene, CTSK, was first isolated in 1996. It is an autosomal recessive osteochondrodysplasia, characterized by disrupted function of osteoclasts. Incidence of this disease is 1.7 per 1 million births with a male to female ratio of 1:1 30% cases arise from consanguineous marriages.
Topics: Consanguinity; Female; Humans; Male; Pycnodysostosis; Rare Diseases
PubMed: 35466658
DOI: 10.55519/JAMC-01-10336