Infantile osteopetrosis, craniosynostosis, and Chiari malformation type I with novel OSTEM1 mutation

We report a case of a 9-month-old Arab infant, with novel OSTEM mutation and unpublished triad of osteopetrosis (OP), craniosynostosis (CS), and Chiari malformation type I (CM1). The index presented with progressive irritability, abnormal movements, following an accidental fall. The history revealed early onset of irritability, progressive visual loss, and global developmental delay, more prominent at the gross motor level and a suspected congenital cytomegalovirus infection. The pregnancy was uneventful with subsequent unremarkable delivery. The parents are Arabs′first cousins with no apparent symptoms or signs of bone disease. Three dimensional brain computed tomography (CT) showed ventriculomegaly, thick calvaria, and CS of the coronal and sagittal sutures. Patient had signs of left lower motor neuron facial palsy, and CT of petrous bones confirms the presence of osteopetrotic petrous with slim mastoid portions of the facial nerve canals both sides. Brain magnetic resonance imaging showed CM1. Skeletal survey showed sclerotic skeleton. He needed ventriculoperitoneal shunt and died at 18 months of age. Molecular testing for OSTEM1 gene revealed novel homozygous mutation that segregated from his parents. This novel OSTEM1 gene novel mutation and the combination of OP, infantile CS, and CM1 is to our knowledge never been reported.