Low-level mesodermal somatic mutation mosaicism: late-onset craniofacial and cervical spinal hyperostoses.

Craniofacial and cervical spinal hyperostoses are rarely seen in the absence of other abnormalities. Only seven patients with isolated cranial hyperostoses have been reported, and only a single patient with both calvarial and cervical vertebral hyperostoses. We report on an adult with late-onset right-sided asymmetrical hyperostoses of the cranium, mandible, and cervical vertebrae in the absence of an AKT1 mutation. At presentation, the patient displayed neither generalized overgrowth nor dysregulated adipose tissue. Standard polymerase chain reaction and Sanger sequencing of DNA extracted from formalin-fixed paraffin-embedded frontal bone and mandibular angular bone was negative for an AKT1 mutation. Though the patient's clinical manifestations did not fulfill the consensus diagnostic criteria of Proteus syndrome, the mosaic distribution of lesions, the sporadic occurrence, and the patient's progressive course were consistent with a somatic mosaicism similar to that syndrome. Hence, the patient's phenotype may have been caused by a very late mesodermal somatic mutation during embryogenesis.