Abstract / Summary
Abstract Background Microcephalic osteodysplastic primordial dwarfism type II (MOPD-II) is a rare autosomal recessive disorder caused by variants in PCNT . It is characterised by severe prenatal and postnatal growth restriction, microcephaly, skeletal anomalies, and distinctive orodental features. Fewer than 150 cases have been reported worldwide and the associated oral and dental anomalies remain poorly defined. Results We present a case of MOPD-II with a novel homozygous PCNT variant (NM_006031.6:c.4522 C > T; p.Gln1508*) inherited from heterozygous parents. The patient displayed extreme growth retardation, microcephaly, skeletal dysplasia, and marked dental abnormalities, including oligodontia, microdontia, enamel hypoplasia, dentin dysplasia, and early root resorption. Dental follow-up began at 17 months of age and included clinical, radiographic, and scanning electron microscopy (SEM) analyses of prematurely exfoliated teeth. SEM revealed aprismatic enamel, dentin mineralisation defects, and abnormal odontoclastic activity. Expression studies in odontoblast-like cells derived from human dental pulp stem cells (hDPSCs), osteoblasts-like cells derived from human bone marrow stem cells (hBMSCs), and murine teeth confirmed PCNT protein localization in ameloblasts, odontoblasts, and osteoblasts during differentiation, supporting its role in tooth and bone development. Conclusion This case underscores the critical role of PCNT in craniofacial and dental development and highlights the value of early dental evaluation in MOPD-II patients. The orodental phenotype is complex and distinctive, supporting the inclusion of dental features in diagnostic criteria. This study contributes to genotype–phenotype correlation efforts and emphasizes the need for multidisciplinary management of rare skeletal dysplasias. Trial registration clinicaltrials.gov , NCT02397824; registered 25 March 2015.