Mutations in ANKRD11 have recently been reported to cause KBG syndrome, an autosomal dominant condition characterized by intellectual disability (ID), behavioral problems, and macrodontia. To understand the pathogenic mechanism that relates ANKRD11 mutations with the phenotype of KBG syndrome, we studied the cellular characteristics of wild-type ANKRD11 and the effects of mutations in humans and mice. We show that the abundance of wild-type ANKRD11 is tightly regulated during the cell cycle, and that the ANKRD11 C-terminus is required for the degradation of the protein. Analysis of 11 pathogenic ANKRD11 variants in humans, including six reported in this study, and one reported in the Ankrd11 Yod/+ mouse, shows that all mutations affect the C-terminal regions and that the mutant proteins accumulate aberrantly. In silico analysis shows the presence of D-box sequences that are signals for proteasome degradation. We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.

OBJECTIVE: To retrospectively assess the clinical exam findings, manifestations, and treatment of concussion in a randomly selected pediatric population at a tertiary care center. BACKGROUND: Pediatric neurotrauma remains an under-acknowledged epidemic among our nation9s youth. Insufficient data has created a barrier, as most patients are given a false sense of security from a negative CT at the ER without ever being evaluated by a neurologist. Access to sports neurology patient records will elucidate the detrimental long-term impact of concussion on the developing pediatric brain. DESIGN/METHODS: To randomly select a population of nineteen concussion patients ages 14 to 19 from a tertiary care center in order to assess: concussion-specific neurologic exam findings, cognitive symptoms (attention, headache, academic performance, short term memory difficulty), sleep disturbances, psychological manifestations, and response to pharmacologic treatment for post-concussion headache. These parameters were chosen to highlight the extensive impact of concussion on pediatric neurologic function. RESULTS: Data from nineteen randomly selected pediatric concussion patients revealed headache and cognitive symptoms to be the most consistent manifestations of post-concussion syndrome, experienced by 89.5[percnt] of patients. Vestibular symptoms were experienced by 73.7[percnt], sleep difficulty 26.3[percnt], and psychological manifestations 31.6[percnt]. Neurologic exam findings revealed sway on Romberg in 30.8[percnt], decreased smooth pursuits 26.3[percnt], and difficulty with single leg BESS 10.5[percnt]. Difficulty with tandem gait increased from 26.3[percnt] to 36.8[percnt] when it was complicated by task switching. Patients were provided most rapid headache relief with triptans and botulinum toxin. CONCLUSIONS: Worsened post-concussion syndrome and delayed recovery were observed in patients who initially exhibited difficulty with Romberg and tandem gait with task switching. Improvements in these clinical exam findings and post-concussion symptoms occurred concurrently. Modified neurologic exam techniques assessing vestibular function therefore served as a prognostic indicator of concussion within this pediatric population. Disclosure: Dr. Cohen has nothing to disclose. Dr. Conidi has nothing to disclose.

OBJECTIVE: To retrospectively assess the clinical exam findings, manifestations, and treatment of concussion in a randomly selected pediatric population at a tertiary care center. BACKGROUND: Pediatric neurotrauma remains an under-acknowledged epidemic among our nation's youth. Insufficient data has created a barrier, as most patients are given a false sense of security from a negative CT at the ER without ever being evaluated by a neurologist. Access to sports neurology patient records will elucidate the detrimental long-term impact of concussion on the developing pediatric brain. DESIGN/METHODS: To randomly select a population of nineteen concussion patients ages 14 to 19 from a tertiary care center in order to assess: concussion-specific neurologic exam findings, cognitive symptoms (attention, headache, academic performance, short term memory difficulty), sleep disturbances, psychological manifestations, and response to pharmacologic treatment for post-concussion headache. These parameters were chosen to highlight the extensive impact of concussion on pediatric neurologic function. RESULTS: Data from nineteen randomly selected pediatric concussion patients revealed headache and cognitive symptoms to be the most consistent manifestations of post-concussion syndrome, experienced by 89.5[percnt] of patients. Vestibular symptoms were experienced by 73.7[percnt], sleep difficulty 26.3[percnt], and psychological manifestations 31.6[percnt]. Neurologic exam findings revealed sway on Romberg in 30.8[percnt], decreased smooth pursuits 26.3[percnt], and difficulty with single leg BESS 10.5[percnt]. Difficulty with tandem gait increased from 26.3[percnt] to 36.8[percnt] when it was complicated by task switching. Patients were provided most rapid headache relief with triptans and botulinum toxin. CONCLUSIONS: Worsened post-concussion syndrome and delayed recovery were observed in patients who initially exhibited difficulty with Romberg and tandem gait with task switching. Improvements in these clinical exam findings and post-concussion symptoms occurred concurrently. Modified neurologic exam techniques assessing vestibular function therefore served as a prognostic indicator of concussion within this pediatric population.