Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor

Shambhavi, Arya; Salian, Smrithi; Shah, Hitesh; Nair, Mohandas; Sharan, Krishna; Jin, Dong‐Kyu; Cho, Sung Yoon; Mathew, Mary; Shukla, Anju; Girisha, Katta M.

doi:10.1055/s-0037-1604100

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…Based on examination of the full texts of these papers, 84 studies 3 4 5 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 ...…”

Section: Resultsmentioning

confidence: 99%

Clinical and radiographic characteristics of pycnodysostosis: A systematic review

Gonzaga,

Costa,

Morais

et al. 2024

Imaging Sci Dent

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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.

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Section: Resultsmentioning

confidence: 99%

Clinical and radiographic characteristics of pycnodysostosis: A systematic review

Gonzaga,

Costa,

Morais

et al. 2024

Imaging Sci Dent

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“…The pathogenic allele (NM_000396.4: c.568C>T, p.(Gln190*)) creates a premature stop codon at position 190 (exon 5 of 8), leading to the production of a truncated transcript that is predicted to undergo nonsense-mediated decay (10). This variant has previously been reported in four other patients (11,12). The detected VUS (NM_000396.4: c263A>C, p.(Gln88Pro)) creates a nonconservative amino acid change from Glycine to Proline at position 88.…”

Section: Discussionmentioning

confidence: 99%

Unique presentation of pycnodysostosis with multisuture craniosynostosis in a Sri Lankan child: a case report

Kolambage,

Cooray,

Subasinghe

et al. 2024

Preprint

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Background: Pycnodysostosis is a rare skeletal dysplasia with autosomal recessive inheritance caused by loss-of-function variants in the CTSK gene. The report represents the first documented case of pycnodysostosis in Sri Lanka, distinguished by its novel and atypical presentation. This expands the known phenotypic spectrum of pycnodysostosis, emphasizing the impact of specific CTSK gene variants on clinical manifestations. Case Presentation: A 2-year-old Sri Lankan boy presented with failure to thrive and multisuture craniosynostosis. This atypical presentation was complicated by increased alkaline phosphatase levels and vitamin D deficiency, without any evidence of fractures. Exome sequencing revealed compound heterozygous variants in the CTSK gene: a pathogenic variant c.568C>T, p.(Gln190*) and a variant of uncertain significance c263A>C, p.(Gln88Pro). Parental testing confirmed autosomal recessive inheritance. The patient underwent surgical correction for craniosynostosis, orbital encephalocele reduction, and received treatment for vitamin D deficiency. Conclusions: The clinical features seen in this patient expand the phenotypic spectrum of pycnodysostosis and deepen the comprehension of the molecular mechanisms driving this uncommon genetic condition. It illustrates the possible impact of specific CTSK gene variants on phenotypic manifestations, such as craniosynostosis. Furthermore, this report provides a comprehensive account of the biochemical parameters of bone metabolism observed in patients previously diagnosed with pycnodysostosis, shedding light on the variability in laboratory findings and emphasizing the need for further investigation into the underlying molecular mechanisms.

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“…Years later, this patient developed new lesions confirmed to be benign fibro-osseous lesions ( 8 ). A second publication describes an adult woman who presented with an incidental finding of a giant cell tumor of her occipital bone ( 9 ). Only the second publication mentions the causative variant in intron 2 of CTSK (c.120 + 1G > T), which does not share a common protein domain with the current patient's variant in exon 8.…”

Section: Discussionmentioning

confidence: 99%

Case report: a giant cell-rich gnathic bone lesion in a child with pycnodysostosis

Spencer,

Makka,

Singh

et al. 2023

Front. Oral. Health

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Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral manifestations are commonly described and include a high-arched palate with dental crowding and malocclusion, hypoplastic enamel, and retained deciduous teeth with impacted permanent teeth, and there is an increased risk of developing osteomyelitis of the jaw. We report here the history of a 9-year-old male with the typical facial and skeletal phenotype of pycnodysostosis but novel oral features. He presented with bilateral progressive facial swelling, which caused functional impairment with chewing and contributed to his severe obstructive sleep apnea (OSA). The severity of his OSA required surgical intervention, and the lesions were resected. Extensive bone remodeling and replacement by fibrous tissue were noted on submucosal dissection, and bilateral subtotal maxillectomies were required. The histopathology of the biopsied lesion was consistent with a giant cell-rich lesion. Genetic testing identified a pathogenic homozygous variant in the CTSK gene, c.953G > A, p. (Cys318Tyr). The proband had a good postsurgical response with sustained improvement in his sleep OSA. We present here the history and clinical characteristics of a patient with typical features of pycnodysostosis and an unusual presentation and histopathology of gnathic bone lesions. This report adds to the body of literature on this rare condition and also highlights the finding of giant cell-rich lesions of the gnathic bones. Giant cell-rich lesions in pycnodysostosis have previously been reported in two cases in the literature. While there is not enough evidence to support a certain association with pycnodysostosis, it is prudent to consider regular oral dental reviews in affected individuals to identify pathology early and avoid such life-threatening complications.

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Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor

Cited by 7 publications

References 22 publications

Clinical and radiographic characteristics of pycnodysostosis: A systematic review

Clinical and radiographic characteristics of pycnodysostosis: A systematic review

Unique presentation of pycnodysostosis with multisuture craniosynostosis in a Sri Lankan child: a case report

Case report: a giant cell-rich gnathic bone lesion in a child with pycnodysostosis

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