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

Abstract

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.