Genetic analysis of posterior cranial fossa morphology in families of Chiari malformation type I

Objective To explore genetic characteristic of posterior cranial fossa morphology in families of Chiari malformation type Ⅰ (CMI). Methods From April 2010 to May 2016, a total of 47 cases of CMI families (CMI group) and their 94 parents (CMI-P group)collected were retrospectively reviewed in Department of Spinal Surgery, Drum Tower Hospital, School of Medicine, Nanjing University.Another cohort of 50 asymptomatic adults was enrolled to serve as the control group.Patients with skull fracture or other diseases which can lead to secondary CMI were excluded.On mid-sagittal T2-weighted magnetic resonance (MR) imaging, four measurements were evaluated and compared between these three groups, including the length of cerebellar tonsillar descent, the area of posterior cranial fossa(PCF area), the area of the brain tissue in posterior cranial fossa (PCF tissue area), and the PCF crowdedness indexes (PCF tissue area/ PCF area×100%). Results Totally 47 CMI patients (21 males and 26 females; mean age, 16.4 years), 94 parents (47 males and 47 females; mean age, 39.2 years) and 50 controls (23 males and 27 females; mean age, 22.3 years) were recruited in this study.Significant differences in all four indexes were found between CMI group and the control group.The length of cerebellar tonsillar descent were much bigger in CMI-P group than in the control group (1.5±2.2 mm vs -0.9±1.1 mm), with 7 cases reach the diagnostic criteria of Chiari malformation(≥5 mm) and one with syingomyelia.Compared to the control group, CMI-P group had smaller PCF area, and its PCF crowdedness indexes averaged 90.0% as between the control group (85.3%) and the CMI group (93.6%). Conclusions In CMI families, parents have similar posterior cranial fossa abnormalities with their CMI children, presenting obviously narrow and crowded.Their PCF crowdedness indexes are between normal subjects and CMI patients, and their cerebellar tonsils are lower, even some parents are also CMI patients, suggesting genetic mechanisms involved in the development of CMI. Key words: Syringomyelia; Cranial fossa, posterior; Heritary diseases; Chiari malformation type Ⅰ