Infantile osteopetrosis, craniosynostosis, and Chiari malformation type I with novel OSTEM1 mutation
A H Mahmoud Adel1, A Al Jabri Abdullah, Faqeih Eissa
1Department of Pediatric Neurology, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.
Insights
A novel OSTEM1 gene mutation caused a rare triad of osteopetrosis, craniosynostosis, and Chiari malformation type I in an infant. This unique genetic finding highlights a new cause for these complex developmental disorders.
Area of Science:
- Genetics
- Pediatrics
- Neurology
Background:
- Osteopetrosis (OP), craniosynostosis (CS), and Chiari malformation type I (CM1) are distinct congenital disorders.
- Genetic mutations are implicated in the pathogenesis of these conditions, but their interplay is not fully understood.
Observation:
- A 9-month-old infant presented with irritability, abnormal movements, visual loss, and developmental delay.
- Clinical examination revealed facial palsy, and imaging confirmed ventriculomegaly, craniosynostosis, osteopetrosis of petrous bones, and Chiari malformation type I.
- The infant's parents were first cousins, suggesting a potential recessive genetic inheritance pattern.
Findings:
- A novel homozygous mutation in the OSTEM1 gene was identified in the infant.
- This mutation segregated with the observed phenotype, linking OSTEM1 to the rare combination of OP, infantile CS, and CM1.
- The identified mutation and the specific triad of congenital anomalies have not been previously reported in medical literature.
Implications:
- This case expands the known spectrum of OSTEM1-related disorders.
- It underscores the importance of genetic testing in complex pediatric cases with overlapping congenital anomalies.
- Further research into OSTEM1 function may elucidate pathogenic mechanisms and inform future therapeutic strategies.
Abstract:
We report a case of a 9-month-old Arab infant, with novel OSTEM mutation and unpublished triad of osteopetrosis (OP), craniosynostosis (CS), and Chiari malformation type I (CM1).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.
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