Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor.
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ABSTRACT:
SUBMITTER: Shambhavi A
PROVIDER: S-EPMC5809170 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
Publications
Pycnodysostosis: Novel Variants in <i>CTSK</i> and Occurrence of Giant Cell Tumor.
Shambhavi Arya A Salian Smrithi S Shah Hitesh H Nair Mohandas M Sharan Krishna K Jin Dong-Kyu DK Cho Sung Yoon SY Mathew Mary M Shukla Anju A Girisha Katta M KM
Journal of pediatric genetics 20170713 1
Pycnodysostosis is an autosomal recessive skeletal dysplasia caused by pathogenic variants in the cathepsin K ( <i>CTSK</i> ) gene. We report seven patients from four unrelated families with this condition in whom we have identified three novel pathogenic variants, c.120 + 1G > T in intron 2, c.399 + 1G > A in intron 4, and c.148T > G (p.W50G) in exon 2, and a known variant, c.568C > T (p.Q190*) in exon 5 of <i>CTSK</i> . We present the clinical, radiographic, and molecular findings of all indiv ...[more]
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Project description: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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