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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 -
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 -
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 the National Medical... Jun 2022
Topics: Humans; Pycnodysostosis
PubMed: 35272848
DOI: 10.1016/j.jnma.2022.02.008 -
Orthodontics & Craniofacial Research Nov 2022To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of...
AIM
To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of the total volume (TV) with other UA morphology variables.
MATERIALS AND METHODS
Cone beam computed tomography (CBCT) images of eight Danish patients with pycnodysostosis (4 males and 4 females with a mean age of 31.8 years, SD: 16.3 years) were analyzed using Mimics (Materialise ) and compared with a sex- and age-matched control group (6 males and 8 females with a mean age of 33.6 years, SD: 18.6 years).
RESULTS
The distance from the tip of the epiglottis (E) to the Frankfurt horizontal plane (Fp) was significantly shorter in the pycnodysostosis group (P < .042). Regarding the cross-sectional measurements, at the 'maximum constriction' (P < .005), the 'upper airway limit' (P < .001) and the 'lower airway limit' (P < .035) cross-sections were significantly smaller in the pycnodysostosis group. The volumes 'nasopharynx' (P < .002) and 'total airway' (TV) (P < .01) were also significantly smaller.
CONCLUSION
Patients with pycnodysostosis have a reduced total airway as well as nasopharyngeal volume compared with matched controls. Additionally, they have a reduced cross-sectional area in the upper and lower borders of the UA, and the area of maximum constriction is also reduced. These factors might explain the high prevalence of obstructive sleep apnoea in pycnodysostosis. Total airway is positively correlated with total length and cross-sections at all levels including the maximum constriction area as well as the anteroposterior dimension at the upper and lower airway borders.
Topics: Adolescent; Adult; Cone-Beam Computed Tomography; Female; Humans; Imaging, Three-Dimensional; Male; Nasopharynx; Pharynx; Pycnodysostosis; Sleep Apnea, Obstructive
PubMed: 34963019
DOI: 10.1111/ocr.12561 -
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 -
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 -
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 -
AACE Clinical Case Reports 2021Pycnodysostosis is commonly associated with growth hormone (GH) deficiency and responds well to GH therapy with achievement of normal or near-normal height and...
OBJECTIVE
Pycnodysostosis is commonly associated with growth hormone (GH) deficiency and responds well to GH therapy with achievement of normal or near-normal height and restoration of body proportions.
CASE REPORT
A 22-month-old extremely short (-4.05 height standard deviation score) disproportionate boy with skeletal dysplasia presented to clinic. Skeletal survey, genetic panel, magnetic resonance imaging, and an insulin-like growth factor generation tests were performed.
RESULTS
Skeletal survey showed increased bone density with classic features of pycnodysostosis, subsequently confirmed to be due to a deleterious homozygous frameshift mutation in . Uniquely among skeletal dysplasias, GH deficiency is a common association, secondary to pituitary hypoplasia. Magnetic resonance imaging confirmed pituitary hypoplasia and he subsequently underwent an insulin-like growth factor generation test that demonstrated biochemical responsiveness to GH therapy. This was thought to be safer than a classic GH stimulation test, in view of his very small size. Subsequently, his height has markedly improved on GH therapy. His height is now -2.25 SD, with an annualized growth velocity of 9.65 cm/y over a period of 18 months .
CONCLUSION
It is important to consider GH therapy in children with pycnodysostosis, with the greatest benefit seen in children started at a young age.
PubMed: 34307842
DOI: 10.1016/j.aace.2021.02.006 -
Revista Espanola de Cirugia Ortopedica... Jun 2021Pycnodysostosis is a rare autosomal recessive disease caused by a mutation in the cathepsin K enzyme gene, a protease that is expressed primarily in osteoclasts and is...
Pycnodysostosis is a rare autosomal recessive disease caused by a mutation in the cathepsin K enzyme gene, a protease that is expressed primarily in osteoclasts and is responsible for bone matrix degradation. The presentation is usually accompanied by short stature, osteoesclerosis, craniofacial dysmorphia and bone fragility. Some papers provide surgical options for fractures of long bones in this type of patients, but none are presenten in European Caucasian patients. The case presented is of a Spanish Caucasian European male with bilateral femoral fracture treated by endomedular nailing.
PubMed: 34175234
DOI: 10.1016/j.recot.2021.01.005