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Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: OMIM 300867) is caused by pathogenic variations in KMT2D or KDM6A. KS is characterized by multiple congenital anomalies and neurodevelopmental disorders. Growth restriction is frequently reported. Here we aimed to create specific growth charts for individuals with KS1, identify parameters used for size prognosis and investigate the impact of growth hormone therapy on adult height. Growth parameters and parental size were obtained for 95 KS1 individuals (41 females). Growth charts for height, weight, body mass index (BMI) and occipitofrontal circumference were generated in standard deviation values for the first time in KS1. Statural growth of KS1 individuals was compared to parental target size. According to the charts, height, weight, BMI, and occipitofrontal circumference were lower for KS1 individuals than the normative French population. For males and females, the mean growth of KS1 individuals was -2 and -1.8 SD of their parental target size, respectively. Growth hormone therapy did not increase size beyond the predicted size. This study, from the largest cohort available, proposes growth charts for widespread use in the management of KS1, especially for size prognosis and screening of other diseases responsible for growth impairment beyond a calculated specific target size. ispartof: AMERICAN JOURNAL OF MEDICAL GENETICS PART A vol:182 issue:3 pages:446-453 ispartof: location:United States status: published

Patrick Manckoundia1,2, France Mourey1,2, Dominic Pérennou2,3, Pierre Pfitzenmeyer1,21Department of Internal Medicine and Geriatrics, University Hospital, Dijon, France; 2INSERM/ERIT-M 0207 Motricity-Plasticity University of Burgundy, Dijon, France; 3Department of Neurological Rehabilitation, University Hospital, Dijon, FranceAbstract: Backward disequilibrium is observed frequently in daily clinical practice. However, there are no epidemiological data concerning this postural disorder. Defined by a posterior position of the centre of mass with respect to the base of support, backward disequilibrium is abnormal postural behavior, usually characterized by a posterior trunk tilt in standing and sitting positions, which predisposes subjects to backward falls. Many afflictions whether they are somatic (degenerative, ischemic and traumatic brain lesions), psychosomatic (psychomotor disadaptation syndrome, confinement to bed, nonuse situations) or psychological (depression) can cause backward disequilibrium. A vicious circle of falls, and loss of autonomy can arise and this is the main consequence of backward disequilibrium. Thus, in this paper, we review backward disequilibrium in elderly subjects with regard to the causes, consequences, assessment, and management.Keywords: backward disequilibrium, balance, elderly subject, falls, posture

International audience; OBJECTIVE: We hypothesised that backward disequilibrium (BD), defined by a posterior position of the centre of mass with respect to the base of support, could be caused by a backward tilt in the perception of verticality. METHODS: The relationship between BD, the perception of verticality, and the history of falls in 25 subjects aged 84.5+/-7.4 years was analysed. An original ordinal scale, the BD scale (BDS), was used to quantify BD. Postural (PV) and haptic verticals (HV) were measured in sagittal plane. RESULTS: BDS scores closely correlated with the number of falls (r = 0.81, p =10(-5)). The more the PV was tilted backward, the greater the BDS scores (r = -0.95, p

International audience; In this study we have quantified the "epileptogenicity" of several brain regions in seizures originating in the posterior parietal cortex in 17 patients investigated by intracerebral recordings using stereotactic EEG (SEEG). Epileptogenicity of brain structures was quantified according to the "epileptogenicity index" (EI), a way to quantify rapid discharges at seizure onset. Seven patients had maximal epileptogenicity in the superior parietal lobule-BA area 7 (Gr1), 2 patients in the superior parietal lobule-area 5 (Gr2), 4 patients in inferior parietal lobule (Gr3) and 4 in the opercular region (Gr4). A large majority of patients (15/17 (88%)) reported to have at least one aura during the course of their disease. Somato-sensory manifestations were reported in the four groups. Vestibular disturbance was observed mainly in seizures from the superior parietal lobule (Gr1 and 2). Ipsilateral version was the most frequent objective manifestation (64%). Hyperkinetic behaviour (motor agitation) was found to be frequent, observed in 4/17 cases (23%) and observed in seizures from inferior parietal regions. In conclusion, the electrophysiological organization and the clinical manifestations of PLS are various and complex. The subjective manifestations are frequent and often suggestive, therefore must be actively sought.

Human idiopathic scoliosis is characterized by severe deformations of the spine and skeleton. The occurrence of vestibular-related deficits in these patients is well established but it is unclear whether a vestibular pathology is the common cause for the scoliotic syndrome and the gaze/posture deficits or if the latter behavioral deficits are a consequence of the scoliotic deformations. A possible vestibular origin was tested in the frogXenopus laevisby unilateral removal of the labyrinthine endorgans at larval stages. After metamorphosis into young adult frogs, X-ray images and three-dimensional reconstructed micro-computer tomographic scans of the skeleton showed deformations similar to those of scoliotic patients. The skeletal distortions consisted of a curvature of the spine in the frontal and sagittal plane, a transverse rotation along the body axis and substantial deformations of all vertebrae. In terrestrial vertebrates, the initial postural syndrome after unilateral labyrinthectomy recovers over time and requires body weight-supporting limb proprioceptive information. In an aquatic environment, however, this information is absent. Hence, the lesion-induced asymmetric activity in descending spinal pathways and the resulting asymmetric muscular tonus persists. As a consequence the mostly cartilaginous skeleton of the frog tadpoles progressively deforms. Lack of limb proprioceptive signals in an aquatic environment is thus the element, which links theXenopusmodel with human scoliosis because a comparable situation occurs during gestationin utero. A permanently imbalanced activity in descending locomotor/posture control pathways might be the common origin for the observed structural and behavioral deficits in humans as in the different animal models of scoliosis.

12 pages, 9 figures, 1 table.-- PMID: 18990727 [PubMed]., This study addressed the hypothesis that the vestibular or lethal toxicities of allylnitrile depend on CYP2E1-mediated bioactivation. Wild-type (129S1) and CYP2E1-null male mice were exposed to allylnitrile at doses of 0, 0.5, 0.75, or 1.0 mmol/kg (po), following exposure to drinking water with 0 or 1% acetone, which induces CYP2E1 expression. Induction of CYP2E1 activity by acetone in 129S1 mice and lack of activity in null mice was confirmed in liver microsomes. Vestibular toxicity was assessed using a behavioral test battery and illustrated by scanning electron microscopy observation of the sensory epithelia. In parallel groups, concentrations of allylnitrile and cyanide were assessed in blood after exposure to 0.75 mmol/kg of allylnitrile. Following allylnitrile exposure, mortality was lower in CYP2E1-null than in 129S1 mice, and increased after acetone pretreatment only in 129S1 mice. This increase was associated with higher blood concentrations of cyanide. In contrast, no consistent differences were recorded in vestibular toxicity between 129S1 and CYP2E1-null mice, and between animals pretreated with acetone or not. Additional experiments evaluated the effect on the toxicity of 1.0 mmol/kg allylnitrile of the nonselective P450 inhibitor, 1-aminobenzotriazole, the CYP2E1-inhibitor, diallylsulfide, and the CYP2A5 inhibitor, methoxsalen. In 129S1 mice, aminobenzotriazole decreased both mortality and vestibular toxicity, whereas diallylsulfide decreased mortality only. In CYP2E1-null mice, aminobenzotriazole and methoxsalen, but not diallylsulfide, blocked allylnitrile-induced vestibular toxicity. We conclude that CYP2E1-mediated metabolism of allylnitrile leads to cyanide release and acute mortality, probably through alpha-carbon hydroxylation, and hypothesize that epoxidation of the beta-gamma double bond by CYP2A5 mediates vestibular toxicity., Ministry of Science and Innovation (Spain)/Fondo Europeo de Desarrollo Regional (European Union) (grant numbers BFU2006-00343/BFI, CGL2005-02846/BOS); Generalitat of Catalonia (grant number 2005SGR00022); and Centre National d'Etudes Spatiales (France) (grant number DAR2006/2007).

OBJECTIVES: To establish during a consensus meeting the fundamental basis, the validity criteria, the main indications and results of the skull vibration induced nystagmus test (SVINT) which explores the vestibule high frequencies. MATERIAL AND METHODS: The SVINT is applied on the mastoid process (right and left sides) at 100 Hz during 10 seconds on a sitting upright subject. Total unilateral peripheral lesions (tUVL: operated vestibular shwannomas, vestibular neurectomies) and partial unilateral peripheral lesions (pUVL: preoperative neuromas, Meniere's disease, vestibular neuritis, chemical labyrinthectomies) were studied. Thirty-six patients had brainstem lesions and 173 normal subjects were used as controls. RESULTS: The SVINT is considered positive when the application of the vibrator produces a reproducible sustained nystagmus always beating in the same direction following several trials in various stimulation topographies (on the right and left mastoid). The skull vibratory nystagmus (SVN) begins and ends with the stimulation; the direction of the nystagmus has no secondary reversal. The slow phase velocity (SPV) is>2 degrees /second. In tUVL the SVINT always reveals a lesional nystagmus beating toward the safe side at all frequencies. The mean SVN SPV is 10.8 degrees /s+/-7.5 SD (N=45). The mastoid site was more efficient than the cervical or vertex sites. Masto?stimulation efficiency is not correlated with the side of stimulation. The SVN SPV is correlated with the total caloric efficiency on the healthy ear. In pUVL the SVINT is positive in 71 to 76% of cases; the mean SVN. SPV (6.7 degrees /s+/-4.7 SD)(N=30) is significantly lower than in tUVL (P=0.0004). SVINT is positive in 6 to 10% of the normal population, 31% of brain stem lesions and negative in total bilateral vestibular peripheral lesions. CONCLUSIONS: SVINT is an effective, rapid and non invasive test used to detect vestibular asymmetry between 20 to 150 Hz stimulation. This test used in important cohorts of patients during the ten last years has demonstrated no observable adverse effect. SVINT complements other tests which evaluate lower frequencies (caloric test: 0,003 Hz) and the medium frequencies (Head-Shaking-Test (HST): 2 Hz; the head impulse test (HIT): 6 Hz). SVINT is useful in the diagnosis of labyrinthine hydrops or detection of acoustic neuromas. It is useful when the caloric test can not be practised because of middle ear problems. SVINT has its limits: in pUVL, the nystagmus direction is not always specific of the pathologic side and can change with the stimulus frequency. This test does not precisely point out the level of the lesion on the vestibular pathway.

OBJECTIVE:: The purpose of this study was to investigate whether Dizziness Handicap Inventory (DHI) score is related to postural performance as assessed by dynamic posturography. STUDY DESIGN:: Retrospective study. SETTING:: Outpatient in a tertiary referral center. PATIENTS:: Ninety-two complete unilateral vestibular loss patients, categorized into 3 groups according to the postlesion stage: 1 to 2 months (n = 32; age, 47.6 +/- 10.7 yr), 4 to 7 months (n= 23; 47.1 +/- 8.37 yr), and 1 year and older (n = 37; 49.2 +/- 9.5 yr). MAIN OUTCOME MEASURES:: Dizziness Handicap Inventory and dynamic balance measured with a seesaw platform moving either in the anterior-posterior or in the mediolateral direction. RESULTS:: The mean DHI score was 25.8 +/- 18.7 and the range was 0 to 68. Dizziness Handicap Inventory scores did not differ significantly between the different unilateral vestibular loss groups studied. No difference was detected between the groups for the 3 subscores (emotional, functional, and physical), except that the older-than-1-year group had a significantly higher physical score than the 2 others. No correlation was found between DHI scores and postural indicators for either direction of the platform. However, patients unable to maintain balance when the seesaw platform moved in the mediolateral direction had significantly higher DHI scores than those who did not fall. CONCLUSION:: Even if they are not directly related, we suggest that DHI and dynamic posturography are complementary approaches for appreciating the vestibular compensation process and are thus useful for postoperative counseling for vestibular loss patients.