Cerebral Palsy

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and a predisposition to cancers. Two unrelated patients, 21- and 16-year-old males, with cleft lip and palate and multiple jaw cysts, were diagnosed according to clinical criteria. To confirm a diagnosis of NBCCS, we undertook a molecular genetic analysis of the PTCH gene. Their PTCH genes were analyzed by direct sequencing of the PCR product from their DNA, and previously unreported mutations were identified. A heterozygous duplication at the nucleotide position between 3325 and 3328 of the PTCH gene (c.3325_3328dupGGCG) was detected in the 21-year-old patient. It caused a frameshift mutation, resulting in a premature termination of the PTCH protein. A point mutation (G to C) in intron 7 of the PTCH gene (c.1067+1G>C) was detected in the 16-year-old patient. This caused an aberrant splicing of PTCH. It is interesting to note that the non-canonical cryptic splice-donor site was activated, which did not conform to the GT-AG rule.Journal of Human Genetics advance online publication, 12 June 2009; doi:10.1038/jhg.2009.51.

Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large- and medium-size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 +/- 2.9 years, BMI: 22.9 +/- 0.3 kg/m(2), mean +/- s.e.m.) and 17 age-matched severely obese (BMI: 41.1 +/- 2.3 kg/m(2)) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross-sectional area (CSA), and media-to-lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 +/- 0.6 vs. 16.2 +/- 0.6 microm, CSA 22,272 +/- 1,339 vs. 15,183 +/- 1,186 microm(2), and media-to-lumen ratio 0.113 +/- 0.006 vs. 0.059 +/- 0.001, respectively, P < 0.01). Acetylcholine-induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (-40.4 +/- 1.3%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.Obesity (2009) doi:10.1038/oby.2009.195.

Objectives: Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). Methods: We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. Results: Significant (multipoint HLOD >/=3.2) or genome-wide-significant (HLOD >/=4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. Conclusions: These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P. Copyright © 2009 S. Karger AG, Basel.

Objective: The objectives of this study were to use a factual basis to: (1) determine the number, nature, and probable phenotypic consequences of karyotype anomalies that would probably be missed (structural anomalies, uncommon aneuploidies and mosaic aneuploidies) by rapid aneuploidy screening (RAS), and (2) appraise whether RAS can replace traditional karyotyping when amniocenteses are performed for increased risk of Down’s syndrome by maternal serum screening or advanced maternal age in the absence of ultrasound abnormality. Methods: This retrospective cohort study analysed the indications, results and outcomes of 5,713 consecutive amniocenteses over a 5-year period at a single prenatal diagnosis centre in Paris. Results: Advanced maternal age and increased Down’s risk with maternal serum marker were the most common indications. Chromosome abnormalities were detected in 3.64% of the pregnancies tested, and unexpected structural anomalies in 0.63% (n = 36). Translocations were more likely to be reciprocal, balanced and of parental origin. There were 6 mosaic gonosomal aneuploidies. Overall, 4 mosaic autosomal aneuploidies and 36 structural aberrations would not have been recognised by RAS alone. Of the 4 mosaic autosomal aneuploidies, all were terminated, one had major malformations and the others had discrete signs that a good quality ultrasound examination would probably not detect. Of the 36 structural aberrations, 24 would be undetected by ultrasound scan, from which 6 would be associated with a significant risk of an abnormal phenotype outcome. Conclusion: In conclusion, our data do not provide evidence that RAS can replace the traditional karyotype. It is probably impossible to arrive in a universal conclusion of which approach (karyotype or RAS) is definitely better than the other. Each prenatal centre could have its own approach depending on the local data analysis, including quality control of ultrasounds. Copyright © 2009 S. Karger AG, Basel.

Objectives: Etiologic diagnosis of multiple congenital abnormalities (MCAs) is often lacking. Large chromosome abnormalities can be detected by conventional cytogenetic methods, but more subtle chromosome micro-rearrangements and/or de novo abnormalities require multi-FISH analysis, which is hampered by the amount of material available in prenatal testing. Methods: We used the comparative genomic hybridization (CGH) array, Genosensor Array 300, to screen for classic microdeletion syndromes and subtelomeric rearrangements in 39 consecutive fetuses with MCAs, after termination of pregnancy, in a prospective study. Thirty-seven of them had a normal karyotype, and two had a de novo unbalanced karyotype that could not be characterized with conventional cytogenetic methods. Results: Two de novo unbalanced karyotypes were characterized by array CGH, and four additional abnormalities were diagnosed: an unbalanced inherited cryptic translocation, a deletion in band 22q11.2, a 1p36 deletion, and a 6p12.1-21.2 duplication. Conclusion: Chromosomal imbalances were therefore detected and/or characterized in 6 of 39 (15.4%) fetuses, indicating the value of routine array CGH in cases of MCAs and in uncharacterized chromosome rearrangements. Extension to all prenatal diagnoses may be warranted when copy number variation is identified and all FISH probes are commercially available. Copyright © 2009 S. Karger AG, Basel.

Objective: The aims of this study were: (1) to explore pregnant women’s background knowledge and expectations of 2nd trimester ultrasound screening, and (2) to investigate women’s intentions to proceed to pregnancy termination if fetal anomaly is detected at the 2nd trimester ultrasound screening. Methods: A prospective, cross-sectional, questionnaire-based study. 300 consecutive pregnant women served as a convenience sample for this study. All the women had had a detailed, 2nd trimester, fetal anomaly scan. The questionnaire was a standardized but not validated, purpose-built structure consisting of five parts: (a) demographics, (b) anamnesis and obstetric history, (c) perceived aim of the scan, (d) expectations from the scan, and (e) intention to terminate pregnancy in case of fetal malformation diagnosis. Statistical analysis was performed with the SPSS 12.0 for Windows. Results: The participants’ mean age was 31.3 (21-45) years. 89.3% of the women filled in the questionnaire. The main reasons for the scan, according to the women, were to exclude fetal abnormalities and to assess the fetal karyotype. The main maternal expectations from the scan were to reduce maternal anxiety and to identify fetal malformations. 75.3% of the women were willing to terminate their pregnancy if fetal abnormalities were detected. Older women more commonly opted for pregnancy termination. Conclusion: The majority of participants have a correct notion about the aim of the ultrasound scan, their expectation is mainly anxiety reduction and a high percentage would proceed to pregnancy termination in the event of the detection of a fetal abnormality. Copyright © 2009 S. Karger AG, Basel.

SYNOPSIS: Neck pain is a common and episodic condition that is treated using a spectrum of interventions known to be moderately effective but is associated with a significant incidence of chronic pain. Recently, there has been increased focus on defining biological aspects of neck pain. Studies have indicated that neurophysiological, biomechanical, and motor control abnormalities are present and may be useful either in prognosis or classification. We review some of these findings in the context of our own work defining biological markers that may form the basis for clinical tests that can be used for prognosis, classification, or outcome evaluation in patients with neck pain. We have identified abnormalities in neurophysiology using quantitative sensory testing (vibration, touch, and current perception) and response to cold provocation that are related to neck disability. We have identified altered muscle biochemistry by measuring circulating muscle proteins in a lumbar surgery model and are now applying those methods to whiplash injury. We have incorporated capnography into treatment to address central physiological changes present in some patients by monitoring and training CO2 levels. We have developed an innovative new test, the Neck Walk Index, that captures abnormal control of head movementduring slow gait as a means of differentiating patients with neck pain from either unaffected controls or individuals with other pathologies. We have used time-varying 3-dimensional joint orientation kinematics to assess deficits in motor control during an upper extremity reach task, the results showing that poor coordination and control of the shoulder girdle leads to shoulder guarding and inconsistencies in elbow joint movement. Despite some promising early results, future research is needed to determine how these measures help clinicians to diagnose, evaluate, and forecast future outcome for patients who present with neck pain. LEVEL OF EVIDENCE: Diagnosis, level 5.Note: Appendices A and B are online-only and are included in this downloadable PDF.J Orthop Sports Phys Ther 2009;39(5):388-399. doi:10.2519/jospt.2009.3126.

Comprehensive medical examinations of 406 junior schoolchildren from 4 Moscow general educational schools during education and an investigation of the spread of poor factors caused by lifestyle and their influence on the functional status, autonomic homeostasis, and adaptive capacities of schoolchildren have established behavioral risk factors for abnormalities at junior school age. Multivariate analytical methods (137 variables) could ascertain the priority and behavioral risk factors in the formation of functional abnormalities in children during primary schooling: an increase in the incidence of abnormalities of the cardiovascular system by 3.5 times, the eye and its appendicular apparatus by 3.5 times, the musculoskeletal system by 4.2 times, and the nervous system by 4.8 times.

Blood gas analysis is frequently requested as part of the point-of-care testing for emergency or critical care patients presenting with metabolic or respiratory abnormalities. With the advent of portable units, information regarding a patient’s acid-base balance and ventilation and oxygenation status can be rapidly obtained.

Meningiomas are extraaxial tumors that arise from the arachnoid layer of the meninges. Seizures are the most common clinical sign in dogs; cats more often present with mentation changes, vision loss, and gait abnormalities. Meningiomas in both species typically have an insidious onset of clinical signs due to their slow growth. Therapy can target the primary tumor with surgery, radiation, and chemotherapy but may be confined to treating its secondary effects.