Comprehensive Clinical, Neuroradiologic, and Oral Health of 23 Individuals With MOPDII

Background and Objectives Microcephalic osteodysplastic primordial dwarfism type II (MOPDII; MIM #210720) is a rare autosomal recessive disorder characterized by severe growth failure and microcephaly, frequently complicated by central nervous system (CNS) anomalies and early-onset cerebrovascular disease. This study aimed to define the neurologic, radiologic, molecular, and oral-dental features of a MOPDII cohort, with particular emphasis on cerebrovascular involvement, and to assess genotype-phenotype correlations. Methods Molecular diagnosis was established using next-generation sequencing, including targeted gene panel sequencing (n = 11) and exome sequencing (n = 1), or Sanger sequencing (n = 11). Clinical data, neuroimaging and vascular findings, systematic oral-dental examinations, and molecular results were retrospectively reviewed. Results Twenty-three patients from 18 unrelated consanguineous families were included. Seventeen distinct homozygous PCNT variants were identified, including 5 splice-site, 5 frameshift, and 7 nonsense variants; of these, 12 were novel. Structural CNS anomalies were common, with the thin corpus callosum being the most frequent finding, observed in 14 of 17 patients (82%) who underwent cranial imaging. Moyamoya disease was identified in 12 patients (70.5%), of whom 7 experienced chronic or acute cerebral infarctions and/or intracranial hemorrhage. Three patients with moyamoya disease died of complications related to vascular involvement. The 2 oldest patients developed severe peripheral arterial and coronary artery occlusions, leading to spontaneous limb amputation and acute myocardial infarction. Oral-dental evaluation, performed in 14 patients (61%), revealed microdontia, malformed teeth, and root shortening. No consistent genotype-phenotype correlation was identified for cerebrovascular or orodental manifestations. Discussion MOPDII is strongly associated with moyamoya disease and represents a major cause of neurologic morbidity and mortality. Early and longitudinal neuroimaging, including brain MRI and angiographic assessment, should be integral to patient management. Oral-dental abnormalities are common and merit routine evaluation.