Extending the Phenotype of Monosomy 1p36 Syndrome and Mapping of a Critical Region for Obesity and Hyperphagia

Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of similar to 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36. (C) 2009 Wiley-Liss, Inc.

Behavioral disturbances in Noonan Syndrome: Brazilian preliminary data

Different from other countries Of Europe and North American, studies about the behavioral profile of Noonan syndrome`s patients are inexistent. The objective of this study was to report the profiles of behavioral functions of 10 participants (4 females and 6 males), with mutations in the PTPN11 gene. For this assessment it was used the Inventory of Behaviors of Children and Adolescents from 6 to 18 years (CBCL/6-18) and the Inventory of Auto-Evaluation for Adults from 18 to 59 years (ASR). The main results point that in Adaptive Functioning Scale all the participants were in the normality range. In the Syndrome Scale the adult participants were in normality range and the children were in clinical range to the sub-scales anxious/depressed, somatic complaints and aggressive behavior. In the DSM-Oriented Scale, 25% of the adult patients were in the borderline clinical range and clinical range, respectively, for Avoidant Personality Problems and Antisocial Personality Problems. About the both children in this scale were in the clinical range of Affective Problems and Anxiety Problems. This relatively homogenous sample, regarding the PTPN11 gene, shows a normal adult behavioral profile, on the average. However, the individual children anti adult profiles show diverse internalizing and externalizing behavioral disturbances.

Final height of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome

The aim of this study was to evaluate the final stature of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome (INS) and the influence of disease-related issues on the achievement of their target heights. We analyzed 60 (41 male) patients and/or their records, with a minimum age of 19 years or at a Tanner`s pubertal stage 4 for boys or status postmenarche for girls, and normal glomerular filtration rate. Mean age at first and last consultation was 5.3 +/- 2.4 years and 20.5 +/- 3.1 years, respectively. Mean follow-up period was 15.10 years. Mean cumulative dose of prednisone was 1254 +/- 831.40 mg/kg. Mean initial and final height Z scores (HtZ) were, respectively, -0.60 +/- 1.0 and -0.64 +/- 0.92 (p = 0.72). The final HtZ showed a significant correlation only with the initial HtZ and the target HtZ (THZ). Six patients achieved a final HtZ below -2, which in male patients correlated strongly to the initial HtZ and THZ. A strong correlation was demonstrated between final HtZ, initial HtZ, and THZ. INS-related issues did not prevent the final stature to reach the predicted target height.

Group psychotherapy: An additional approach to burning mouth syndrome

Introduction: Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease. Objectives: Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. Casuistics and Methods: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy. Results: There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04). Conclusion: Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods. (C) 2009 Elsevier Inc. All rights reserved.

Dental Evaluation of Kabuki Syndrome Patients

Kabuki syndrome is a genetic disorder of unknown etiology characterized by mental retardation, growth deficiency, and peculiar face (i.e., long palpebral fissures, eversion of the lateral third of the lower eyelids, prominent ears, and broad and depressed nasal tip). Oral manifestations commonly observed in Kabuki syndrome may comprise cleft lip/palate, bifid tongue and uvula, malocclusion, and dental abnormalities. We evaluated the dental findings of eight patients with Kabuki syndrome. One presented cleft palate; three presented caries; and seven had missing teeth, with the upper lateral incisors and inferior central incisors being the most commonly absent. All missing teeth were permanent, and there was no alteration of dental chronology or morphology. Because most patients had mixed dentition, the presence or absence of primary teeth was assessed through the parents` reports. One patient presented an absent upper canine, which had not been reported previously in the literature. Dental findings may be helpful for clinical diagnosis, or they may be an additional finding to substantiate the diagnosis of Kabuki syndrome in children with mild phenotype.

Ultrasound evaluation of prognosis in fetuses with posterior urethral valves

Purpose: The aim of this study was to evaluate the ability of prenatal ultrasound markers to predict postnatal renal prognosis in fetuses with posterior urethral valves. Methods: Medical files on fetuses with prenatal diagnosis of posterior urethral valves from 2000 to 2006 were reviewed retrospectively. Data from prenatal follow-up included gestational age at diagnosis, ultrasound renal parenchyma evaluation, and presence and time of oligohydramnios onset. Prenatal parameters studied were correlated to postnatal renal function. Results: Thirty-one male fetuses were included. Six pregnancies were terminated. Of the remaining 25 pregnancies that were continued, 4 children had abnormal creatine and 21 normal creatinine levels at follow-up. Presence and time of oligohydramnios onset did not differ between groups (P = .43). Ultrasound detected bilateral renal abnormalities in 3 fetuses (75%) with altered renal function, and 10 fetuses (55%) with normal creatinine, at follow-up. Conclusions: None of the ultrasound parameters evaluated were able to reliably predict postnatal renal function. (C) 2011 Elsevier Inc. All rights reserved.

TRANSFER OF A FASCICLE FROM THE POSTERIOR CORD TO THE SUPRASCAPULAR NERVE AFTER INJURY OF THE UPPER ROOTS OF THE BRACHIAL PLEXUS: TECHNICAL CASE REPORT

OBJECTIVE: A new nerve transfer technique using a healthy fascicle of the posterior cord for suprascapular nerve reconstruction is presented. This technique was used in a patient with posttraumatic brachial plexopathy resulting in upper trunk injury with proximal root stumps that were unavailable for grafting associated with multiple nerve dysfunction. CLINICAL PRESENTATION: A 45-year-old man sustained a right brachial plexus injury after a bicycle accident. Clinical evaluation and electromyography indicated upper trunk involvement. Trapezius muscle function and triceps strength were normal on physical examination. INTERVENTION: The patient underwent a combined supra- and infraclavicular approach to the brachial plexus. A neuroma-in-continuity of the upper trunk and fibrotic C5 and C6 roots were identified. Electrical stimulation of the phrenic and spinal accessory nerves produced no response. The suprascapular nerve was dissected from the upper trunk, transected, and rerouted to the infraclavicular fossa. A healthy fascicle of the posterior cord to the triceps muscle was transferred to the suprascapular nerve. At the time of the 1-year follow-up evaluation, arm abduction against gravity and external rotation reached 40 and 34 degrees, respectively. CONCLUSION: The posterior cord can be used as a source of donor fascicle to the suprascapular nerve after its infraclavicular relocation. This new intraplexal nerve transfer could be applied in patients with isolated injury of the upper trunk and concomitant lesion of the extraplexal nerve donors usually used for reinnervation of the suprascapular nerve.

Role of ankle mobility in foot rollover during gait in individuals with diabetic neuropathy

Background: The purpose of this study was to investigate the ankle range of motion during neuropathic gait and its influence on plantar pressure distribution in two phases during stance: at heel-strike and at push-off. Methods: Thirty-one adults participated in this study (control group, n = 16; diabetic neuropathic group, n = 15). Dynamic ankle range of motion (electrogoniometer) and plantar pressures (PEDAR-X system) were acquired synchronously during walking. Plantar pressures were evaluated at rearfoot. midfoot and forefoot during the two phases of stance. General linear model repeated measures analysis of variance was applied to investigate relationships between groups, areas and stance phases. Findings: Diabetic neuropathy patients walked using a smaller ankle range of motion in stance phase and smaller ankle flexion at heel-strike (P = 0.0005). Peak pressure and pressure-time integral values were higher in the diabetic group in the midfoot at push-off phase when compared to heel-strike phase. On the other hand, the control group showed similar values of peak pressure in midfoot during both stance phases. Interpretation: The ankle mobility reduction observed could be associated to altered plantar pressure distribution observed in neuropathic subjects. Results demonstrated that midfoot and forefoot play a different role in subjects with neuropathy by receiving higher loads at push-off phase that are probably due to smaller ankle flexion at stance phase. This may explain the higher loads in anterior areas of the foot observed in diabetic neuropathy subjects and confirm an inadequate foot rollover associated to the smaller ankle range of motion at the heel-strike phase. (C) 2009 Elsevier Ltd. All rights reserved.

MLPA analysis in 30 Sotos syndrome patients revealed one total NSD1 deletion and two partial deletions not previously reported

Sotos syndrome (MIM #117550) is an autosomal dominant condition characterized by pre and postnatal overgrowth, macrocephaly and typical facial gestalt with frontal bossing, hypertelorism, antimongoloid slant of the palpebral fissures, prominent jaw and high and narrow palate. This syndrome is also frequently associated with brain, cardiovascular, and urinary anomalies and is occasionally accompanied by malignant lesions such as Wilms turnout and hepatocarcinoma. The syndrome is known to be caused by mutations or deletions of the NSD1 gene. To detect both 5q35 microdeletions and partial NSD1 gene deletions we screened 30 Brazilian patients with clinical diagnosis of Sotos syndrome by multiplex ligation dependent probe amplification. We identified one patient with a total deletion of NSD1 and neighbouring FGFR4, other with missing NSD1 exons 13-14 and another with a deletion involving FGFR4 and spanning up to NSD1 exon 17. All deletions were de novo. The two NSD1 partial deletions have not been previously reported. The clinical features of the three patients included a typical facial gestalt with frontal bossing, prominent jaw and high anterior hairline; macrocephaly, dolichocephaly, large hands; neonatal hypotonia and jaundice. All presented normal growth at birth but postnatal overgrowth. Two patients with NSD1 and FGFR4 gene deletions presented congenital heart anomalies. (C) 2009 Elsevier Masson SAS. All rights reserved.

Effects of Oropharyngeal Exercises on Patients with Moderate Obstructive Sleep Apnea Syndrome

Rationale: Upper airway muscle function plays a major role in maintenance of the upper airway patency and contributes to the genesis of obstructive sleep apnea syndrome (OSAS). Preliminary results suggested that oropharyngeal exercises derived from speech therapy may be an effective treatment option for patients with moderate OSAS. Objectives: To determine the impact of oropharyngeal exercises in patients with moderate OSAS. Methods: Thirty-one patients with moderate OSAS were randomized to 3 months of daily (similar to 30 min) sham therapy (n = 15, control) or a set of oropharyngeal exercises (n = 16), consisting of exercises involving the tongue, soft palate, and lateral pharyngeal wall. Measurements and Main Results: Anthropometric measurements, snoring frequency (range 0-4), intensity (1-3), Epworth daytime sleepiness (0-24) and Pittsburgh sleep quality (0-21) questionnaires, and full polysomnography were performed at baseline and at study conclusion. Body mass index and abdominal circumference of the entire group were 30.3 +/- 3.4 kg/m(2) and 101.4 +/- 9.0 cm, respectively, and did not change significantly over the study period. No significant change occurred in the control group in all variables. In contrast, patients randomized to oropharyngeal exercises had a significant decrease (P < 0.05) in neck circumference (39.6 +/- 3.6 vs. 38.5 +/- 4.0 cm), snoring frequency (4 [4-4] vs. 3 [1.5-3.5]), snoring intensity (3 [3-4] vs. 1 [1-2]), daytime sleepiness (14 +/- 5 vs. 8 +/- 6), sleep quality score (10.2 +/- 3.7vs. 6.9 +/- 2.5), and OSAS severity (apnea-hypopnea index, 22.4 +/- 4.8 vs. 13.7 +/- 8.5 events/h). Changes in neck circumference correlated inversely with changes in apnea-hypopnea index (r = 0.59; P < 0.001). Conclusions: Oropharyngeal exercises significantly reduce OSAS severity and symptoms and represent a promising treatment for moderate OSAS. Clinical trial registered with www.clinicaltrials.gov (NCT 00660777).

Treatment of obstructive sleep apnea syndrome in patients from a teaching hospital in Brazil: is it possible?

The aim of this study was to evaluate the efficacy of a cost-effective intra-oral appliance for obstructive sleep apnea syndrome built into a large teaching hospital. Out of 20 evaluated and treated patients, 14 concluded the study: eight men and six women, with a mean age of 42-46 (mean + SD) years and mean body mass index of 27.66. Inclusion criteria were mild or moderate apnea-hypopnea index (AHI) according to a polysomnographic study. All patients were treated with the monobloco intra-oral appliance. They were then submitted to a follow-up polysomnographic study after 60 days using the appliance. An orofacial clinical evaluation was carried out with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) questionnaire and with clinical evaluation questionnaire devised by the Orofacial Pain Team before and 60 days after fitting the intra-oral appliance. The AHI showed a statistically meaningful (p = 0.002) reduction from 15.53 to 7.82 events per hour, a non-statistically significant oxygen saturation increase from 83.36 to 84.86 (p = 0.09), and Epworth`s sleepiness scale reduction from 9.14 to 6.36 (p = 0.001). Three patients did not show any improvement. The most common side effect during the use of the appliance/device was pain and facial discomfort (28.57%), without myofascial or temporomandibular joint pain as evaluated by the RDC/TMD questionnaire. The intra-oral device produced a significant reduction of the apnea-hypopnea index during the study period with the use of the monobloco intra-oral appliance. Patients did not show prior myofascial pain or 60 days after use of the intra-oral appliance.

GIANT FUSIFORM ANEURYSM ARISING FROM FENESTRATED POSTERIOR CEREBRAL ARTERY AND BASILAR TIP VARIATION: CASE REPORT

OBJECTIVE: A giant fusiform aneurysm in the posterior cerebral artery (PCA) is rare, as is fenestration of the PCA and basilar apex variation. We describe the angiographic and surgical findings of a giant fusiform aneurysm in the P1-P2 PCA segment associated with PCA bilateral fenestration and superior cerebellar artery double origin. CLINICAL PRESENTATION: A 26-year-old woman presented with a 2-month history of visual blurring. Digital subtraction angiography showed a giant (2.5 cm) fusiform PCA aneurysm in the right P1-P2 segment. The 3-dimensional view showed a caudal fusion pattern from the upper portion of the basilar artery associated with a bilateral long fenestration of the P1 and P2 segments and superior cerebellar artery double origin. INTERVENTION: Surgical trapping of the right P1 -P2 segment, including the posterior communicating artery, was performed by a pretemporal approach. Angiograms performed 3 and 13 months after surgery showed complete aneurysm exclusion, and the PCA was permeated and filled the PCA territory. Clinical follow-up at 14 months showed the patient with no deficits and a return to normal life. CONCLUSION: To our knowledge, this is the first report of a giant fusiform aneurysm of the PCA associated with P1-P2 segment fenestration and other variations of the basilar apex (bilateral superior cerebellar artery duplication and caudal fusion). Comprehension of the embryology and anatomy of the PCA and its related vessels and branches is fundamental to the decision-making process for a PCA aneurysm, especially when parent vessel occlusion is planned.

Study into the use of continuous positive airway pressure in obstructive sleep apnoea-hypopnoea syndrome patients with daytime drowsiness

Background: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is a respiratory disorder with high morbidity and mortality. Continuous positive airway pressure (CPAP) is the most commonly prescribed conservative treatment for adults with OSAHS. CPAP therapy normalises or decreases OSAHS symptoms and can reduce and prevent OSAHS complications. Aims: To evaluate adherence to nasal CPAP treatment and CPAP impact on daytime drowsiness. Method: A sample of 20 patients evaluated for daytime drowsiness using the Epworth sleepiness scale and interviewed for adherence to nasal CPAP use. Results: There was a significant decrease in the level of daytime sleepiness of the patients users of nasal CPAP (p=0.017); patients not using nasal CPAP experienced a decrease without statistical significance (p=0.162). 100% of CPAP users reported benefits and 50% of these reported related discomforts. Conclusions: Patients with OSAHS that use CPAP have a greater reduced level of sleepiness than those who do not use it.

Tentorial Posterior Fossa Meningioma Which Is the Ideal Surgical Approach: Supra/Infratentorial Combined or Retrosigmoid?

Tentorial meningiomas account for 2% to 3% of all intracranial meningiomas. The authors present their experience with posterior fossa tentorial meningiomas, and discuss the main features, which influence approaches and complications of the different surgical techniques. Twenty-four patients had meningiomas localized predominantly in posterior fossa. Their historical records and radiologic examinations were reviewed in accordance with Simpson`s classification. The extension of tumor removal was Simpson grade I in 12 patients (50%), grade II in 12 patients (50%), and grades III and IV in none of the patients. In 22 patients (91.66%), the meningioma was classified as grade I and in 2 cases (8.33%) classified as grade 11 (atypical meningioma). The combined supra/infiratentorial was employed in 12 cases, and complete resections were most common with this approach compared with retrosigmoid technique. Postoperative complications occurred in 10 patients (41.6%) with major deficits in 3 patients (12.5%). The authors believe that careful preoperative choice of the surgical approach should be based Oil tumor location and extension. It is then possible to achieve the best radical microsurgical tumor resection, avoiding additional injury to neurovascular structures.