The exact pathogenesis of Arnol-Chiari malformation is not fully understood but It is thought that Arnol-Chiari malformation is the result of bone developmental abnormalities or mesodermal growth and differentiation abnormalities. Genes involved in the pathogenesis of Arnold-Chiari malformation include PAX1, PAX2, PAX3, PAX6, FGF2, TBX6, HOX gene, Noggin gene, and EFNB1. Conditions associated with Arnold-Chiari malformation include hydrocephalus, syringomyelias,Tethered spinal cord syndrome, neurofibromatosis type 1, Noonan syndrome, Pierre Robin sequence, Klippel-Feil syndrome, Albright hereditary osteodystrophy, x-linked aqueductal stenosis, Goldenhar syndrome, Williams syndrome, Shprintzen- goldberg syndrome, achondroplasia, familial osteosclerosis, velocardiofacial syndrome, and connective tissue disorders.

• The exact pathogenesis of Arnol-Chiari malformation is not fully understood but It is thought that Arnol-Chiari malformation is the result of cascade of anomalies that lead to:
  • Bone developmental abnormalities
  • Mesodermal growth and differentiation abnormalities
• These anomalies can be congenital as a result of developmental error or acquired.
• All the potential causes of Chiari malformation will lead to posterior cranial fossa abnormalities and subsequently herniation of cerebellar and/or other structures from foramen magnum.

• Genes involved in the pathogenesis of Arnold-Chiari malformation include:^[1]
  • PAX1
  • PAX2
  • PAX3
  • PAX6
  • FGF2
  • TBX6
  • HOX gene
  • Noggin gene
  • EFNB1
• There are many findings emphasizing on genetic basic of Chiari malformation including:
  • Many studies described higher prevalence of Chiari malformation among mono zygote twins or between family members.
  • There are some evidence showing autosomal dominant/ recessive transmission.
  • There are many genetic conditions that have association with Chiari malformation.

Conditions associated with Arnold-Chiari malformation include:^{[2][3][4][5][6][7]}

• Hydrocephalus
• Syringomyelias
• Tethered spinal cord syndrome
• Neurofibromatosis type 1
• Noonan syndrome
• Pierre Robin sequence
• Klippel-Feil syndrome
• Albright hereditary osteodystrophy
• X-linked aqueductal stenosis
• Goldenhar syndrome
• Williams syndrome
• Shprintzen- goldberg syndrome
• Achondroplasia
• Familial osteosclerosis
• Velocardiofacial syndrome
• Connective tissue disorders such as:
  • Ehlers-Danlos syndrome
  • Marfan Syndrome.

On gross pathology, there is no characteristic finding of Chiari malfromation.

On microscopic pathology, there is enlaged, dysplastic / reactive fibrous tissue and choroid plexus in a Chiari II malformation.