Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Noninvasive Assessment of Hemodynamic Stress Distribution after Indirect Revascularization for Pediatric Moyamoya Vasculopathy.

BACKGROUND AND PURPOSE: Indirect revascularization surgery is an effective treatment in children with Moyamoya vasculopathy. In the present study, we hypothesized that DSC-PWI may reliably assess the evolution of CBF-related parameters after revascularization surgery, monitoring the outcome of surgical pediatric patients with Moyamoya vasculopathy. Thus, we aimed to evaluate differences in DSC-PWI parameters, including the hemodynamic stress distribution, in surgical and nonsurgical children with Moyamoya vasculopathy and to correlate them with long-term postoperative outcome. MATERIALS AND METHODS: Pre- and postoperative DSC parameters of 28 patients (16 females; mean age, 5.5 ± 4.8 years) treated with indirect revascularization were compared with those obtained at 2 time points in 10 nonsurgical patients (6 females; mean age, 6.9 ± 4.7 years). We calculated 4 normalized CBF-related parameters and their percentage variance: mean normalized CBF of the MCA territory, mean normalized CBF of the proximal MCA territory, mean normalized CBF of cortical the MCA territory, and hemodynamic stress distribution. The relationship between perfusion parameters and postoperative outcomes (poor, fair, good, excellent) was explored using 1-way analysis of covariance (P < .05). RESULTS: A significant decrease of the mean normalized CBF of the proximal MCA territory and hemodynamic stress distribution and an increase of the mean normalized CBF of the cortical MCA territory were observed after revascularization surgery (P < .001). No variations were observed in nonsurgical children. Postoperative hemodynamic stress distribution and its percentage change were significantly different in outcome groups (P < .001). CONCLUSIONS: DSC-PWI indices show postoperative hemodynamic changes that correlate with clinical outcome after revascularization surgery in children with Moyamoya disease.

Comparative study between biodegradable nasopore (BNP) and Merocel hemox 10 cm after septo-turbinoplasty procedure.

OBJECTIVE: The purpose of our study was to compare Merocel (Merocel Hemox 10 cm) and BNP (biodegradable nasopore) during a septoturbinoplasty procedure in terms of efficiency and patient comfort. PATIENTS AND METHODS: We carried out a retrospective review of 72 patients who had undergone septoturbinoplasty between January 2015 and January 2016. Each group, packed with BNP or Merocel Hemox 10 cm was composed of 36 patients. A standard visual analogue scale ranging from zero (no symptoms) to 10 (the most severe symptoms) was used to assess subjective symptoms. To compare the usefulness of materials we evaluated the postoperative bleeding, infection and adhesion after the removal of packing with and endoscopic examination using a 5-point scale (zero, absent; 1, mild; 2, moderate; 3, severe; and 4, very severe). Secretions and crusts were evaluated 1 week and 4 weeks after surgery in both groups using a 5-point scale (zero, absent; 1, mild; 2, moderate; 3, severe; and 4, very severe). RESULTS: A total of 72 patients were enrolled in the study, 45 women and 27 men; age range 15-78 with a mean age of 47 years. In the group A (Merocel group), 21 cases showed grade 1 bleeding (58%), 11 cases grade 2 (30%) and 4 patients grade 0 (11.1%). In the group B (BNP group), 29 cases showed grade 0 bleeding (80.56%) and 7 cases showed grade 1 bleeding (19.44%). There was a statistical significant difference between the Merocel group and the BNP group in terms of bleeding after removal of packing material (p < 0.05). In the group A, 16 patients developed mild adhesion (44%), 8 patients moderate adhesion (22.2%), 3 patients severe adhesion (8.33%) and 1 patient very severe adhesion (2.77%). BNP nasal packing didn't cause any adhesion in 25 patients (69.4%), 11 patients developed mild adhesion (30.5%). So there was a statistical significant difference between group A and group B regarding the adhesion (p < 0.05). There was a statistically significance reduction of nasal secretions and crusts at a week after surgery in the BNP group vs. Merocel group. The difference is not statistically significant 4 weeks after surgery. About the severity of symptoms related to nasal packing, we found a statistically significant difference (p < 0.05) between Merocel and BNP group regarding the pain during packing removal, the general satisfaction and the pressure. CONCLUSIONS: Biodegradable nasopore reduced pain and patient discomfort during packing removal and causes less bleeding compared to Merocel hemox 10 cm. This type of material can be used after septoturbinolplasty.

Vein of Galen aneurysmal malformation (VGAM) in the fetus: retrospective analysis of perinatal prognostic indicators in a two-center series of 49 cases.

OBJECTIVE: Vein of Galen aneurysmal malformation (VGAM) is a rare fetal anomaly, the neurological outcome of which can be good with appropriate perinatal management. However, most fetal series are too small to allow reliable statistical assessment of potential prognostic indicators. Our aim was to assess, in a two-center series of 49 cases, the prognostic value of several prenatal variables, in order to identify possible prenatal indicators of poor outcome, in terms of mortality and cerebral disability. METHODS: This was a retrospective study involving 49 cases of VGAM diagnosed prenatally and managed at two centers over a 17-year period (1999-2015). All cases had undergone detailed prenatal cerebral and cardiac assessment by grayscale ultrasound, color and pulsed-wave Doppler and magnetic resonance imaging (MRI). Ultrasound and MRI examination reports and images were reviewed and outcome information was obtained from medical reports. Volume of the VGAM (on ultrasound and MRI) was calculated and development of straight-sinus dilatation, ventriculomegaly and other major brain abnormalities was noted. Cardiothoracic ratio, tricuspid regurgitation and reversed blood flow across the aortic isthmus were evaluated on fetal echocardiography. Major brain lesions were considered by definition to be associated with poor outcome in all cases. Pregnancy and fetoneonatal outcome were known in all cases. Fetoneonatal outcome and brain damage were considered as dependent variables in the statistical evaluation. Poor outcome was defined as death, late termination of pregnancy due to association with related severe brain anomalies or severe neurological impairment. RESULTS: At a mean follow-up time of 20 (range, 0-72) months, 36.7% of the whole series and 52.9% of the cases which did not undergo late termination were alive and free of adverse sequelae. Five (10.2%) cases showed progression of the lesion between diagnosis and delivery. On univariate analysis, dilatation of the straight sinus, VGAM volume ≥ 20 000 mm3 and tricuspid regurgitation were all significantly related to poor outcome. However, on logistic regression analysis, the only variables associated significantly with poor outcome were tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 . The former was also the only variable associated with brain damage. CONCLUSIONS: Major brain lesions, tricuspid regurgitation and, to a lesser extent, VGAM volume ≥ 20 000 mm3 are the only prenatal variables associated with poor outcome in fetal VGAM. Prenatal multidisciplinary counseling should be based on these variables. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Barreras para la implementación de la Atención Farmacéutica en establecimientos farmacéuticos de Cusco, Perú / Barriers to the implementation of pharmaceutical care in pharmacies in Cusco, Peru

Introducción: Después de más de 25 años de la propuesta de Atención Farmacéutica, un gran porcentaje de establecimientos farmacéuticos no logran la implementación, siendo necesario determinar las barreras usuales para formular estrategias que permitan la implementación y desarrollo. Objetivos: Determinar los factores que impiden la implementación de la Atención Farmacéutica en establecimientos farmacéuticos en los distritos de Cusco y Wanchaq, departamento de Cusco. Material y métodos: Estudio observacional, descriptivo y transversal, realizado mediante una encuesta dirigida a 95 químicos farmacéuticos colegiados en Cusco (distrito Cusco: 44; distrito Wanchaq: 51) y que laboran en farmacias y boticas y asimismo a 46 propietarios de farmacias y boticas. Se elaboraron dos fichas de recolección de datos (cuestionario y encuesta) que fueron validados por expertos. Los resultados obtenidos se procesaron en el programa estadístico SPSS V.22. Resultados: El 63,2% de los químico farmacéuticos fueron mujeres, la edad promedio fue 32.2 (DE: 6.027). Ninguno de los químicos farmacéuticos realizaron maestría o doctorado en Atención Farmacéutica; solo es 7.4% realizó un diplomado en Atención Farmacéutica. El 88.4% estaba satisfecho con la elección de su profesión; el 93.7% afirma que la formación universitaria no es suficiente para realizar la Atención Farmacéutica. El 81.1% está insatisfecho con el ingreso mensual que percibe. Conclusión: La falta de materiales e infraestructura, insuficiente tiempo, mal salario y la necesidad de aprobación de los propietarios fueron los factores fundamentales que impiden la implementación de la Atención Farmacéutica

Introduction: More than 25 years after the pharmaceutical care proposal, a large percentage of pharmacies fail to its implementation which makes necessary to determine the usual barriers to create strategies that contribute to its setting-up and its development. Objectives: To determine the factors impeding the implementation of pharmaceutical care in pharmacies in Cusco and Wanchaq districts, Cusco’s department. Methods: It was carried out an observational, descriptive and cross-sectional study based on a survey addressed to 95 pharmaceutical chemists registered in Cusco (Cusco district: 44; Wanchaq district: 51) who work in pharmacies and also to 46 pharmacies’ owners. Two pieces of data collection (questionnaire survey) validated by experts were developed. The results were processed in SPSS V.22. Results: 63.2% of the pharmaceutical chemists were women, the mean age was 32.2 (SD: 6.027). None of them did a master or a doctorate in pharmaceutical care. Just 7.4% held a diploma in pharmaceutical care. 88.4% were satisfied with the occupation of their choice; 93.7% said that university education is not enough for pharmaceutical care development. 81.1% are dissatisfied with the monthly income received. Conclusion: The lack of materials and infrastructure, the insufficient time, the poor wages and the need for approval of the owners were the key factors that prevent the implementation of pharmaceutical care

Expanding the mutational spectrum associated to neural tube defects: literature revision and description of novel VANGL1 mutations.

BACKGROUND: Neural Tube Defects (NTD) are a common class of birth defects that occur in approximately 1 in 1000 live births. Both genetic and nongenetic factors are involved in the etiology of NTD. Planar cell polarity (PCP) genes plays a critical role in neural tube closure in model organisms. Studies in humans have identified nonsynonymous mutations in PCP pathway genes, including the VANGL genes, that may play a role as risk factors for NTD. METHODS: Here, we present the results of VANGL1 and VANGL2 mutational screening in a series of 53 NTD patients and 27 couples with a previous NTD affected pregnancy. RESULTS: We identified three heterozygous missense variants in VANGL1, p.Ala187Val, p.Asp389His, and p.Arg517His, that are absent in controls and predicted to be detrimental on the protein function and, thus, we expanded the mutational spectrum of VANGL1 in NTD cases. We did not identify any new variants having an evident pathogenic effect on protein function in VANGL2. Moreover, we reviewed all the rare nonsynonymous or synonymous variants of VANGL1 and VANGL2 found in patients and controls so far published and re-evaluated them for their pathogenic role by in silico prediction tools. Association tests were performed to demonstrate the enrichment of deleterious variants in reviewed cases versus controls from Exome Variant Server (EVS). CONCLUSION: We showed a significant (p = 7.0E-5) association between VANGL1 rare genetic variants, especially missense mutations, and NTDs risk.

Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

Glioneuronal tumors and epilepsy in children: seizure outcome related to lesionectomy.

AIM: Glioneuronal tumors (especially gangliogliomas and dysembryoplastic neuroepithelial tumors) are an increasingly recognised cause of drug-resistant epilepsy in children. The optimal surgical strategy (lesionectomy vs. extended resection of epileptogenic peritumoral areas) to obtain seizure control has not been fully established. Our aim was to analyze the post-surgical seizure outcome in children with epileptogenic glioneuronal tumors related to lesionectomy. METHODS: The clinical data were collected through a database. Video-EEG and MRI were performed in all patients pre-operatively and at the follow-up. RESULTS: Our series included 22 patients. The age range at surgery was 10 months-16 years (mean: 6.5±4.5 years). Epilepsy duration ranged 1-78 months (mean: 11.6±17.0). There were complex partial seizures in 14 cases, simple partial seizures in 6 patients and generalized epilepsy in 2. Gross-total surgical removal was achieved in 15 (68.2%) patients. At the last follow-up (mean 4.7 years), 20 (90.9%) patients were seizure-free (Engel Class I) and two (9.1%) were Engel Class III. Six out of seven (85.7%) patients with subtotal removal were Engel Class I. Statistical analysis failed to detect any difference between seizure outcome (Engel Class) and tumor type (DNT vs. GG; P=1.00) or location (temporal vs. non temporal; P=0.51), and extension of the resection (total vs. subtotal; P=1.00). CONCLUSION: Primary aim of the surgery for epileptogenic glioneuronal tumors is to remove the lesion and to obtain a complete seizure control. However, if a complete tumor resection cannot be carried out, a subtotal removal of the lesion can equally provide satisfactory results.

IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants.

AIMS/HYPOTHESIS: The aim of the study was to determine the association between IRS1 G972R polymorphism and type 2 diabetes; published data concerning this association have been conflicting. To obtain further insight into this topic, we performed a meta-analysis of all available case-control studies. METHODS: We performed a meta-analysis of 32 studies (12,076 cases and 11,285 controls). RESULTS: The relatively infrequent R972 variant was not significantly associated with type 2 diabetes (OR 1.09, 95% CI 0.96-1.23, p = 0.184 under a dominant model). Some evidence of heterogeneity was observed across studies (p = 0.1). In the 14 studies (9,713 individuals) in which the mean age at type 2 diabetes diagnosis was available, this variable explained 52% of the heterogeneity (p = 0.03). When these studies were subdivided into tertiles of mean age at diagnosis, the OR for diabetes was 1.48 (95% CI 1.17-1.87), 1.22 (95% CI 0.97-1.53) and 0.88 (95% CI 0.68-1.13) in the youngest, intermediate and oldest tertile, respectively (p = 0.0022 for trend of ORs). CONCLUSIONS/INTERPRETATION: Our findings illustrate the difficulties of ascertaining the contribution of 'low-frequency-low-risk' variants to type 2 diabetes susceptibility. In the specific context of the R972 variant, approximately 200,000 study individuals would be needed to have 80% power to identify a 9% increase in diabetes risk at a genome-wide significance level. Under these circumstances, a strategy aimed at improving outcome definition and decreasing its heterogeneity may critically enhance our ability to detect genetic effects, thereby decreasing the required sample size. Our data suggest that focusing on early-onset diabetes, which is characterised by a stronger genetic background, may be part of such a strategy.

Successful isolation and long-term establishment of a cell line with stem cell-like features from an anaplastic medulloblastoma.

AIMS: Herein we report on the successful isolation and establishment of a novel, long-term, primary, neurosphere-like cell line called 1603-MED from a 5-year-old boy affected by a highly aggressive anaplastic medulloblastoma. METHODS: Elaboration of the new protocol for neurosphere assay is extensively discussed, together with a complete immuno-histochemical and cytogenetic characterization of 1603-MED. RESULTS: Clinical course and histopathology are briefly discussed. The 1603-MED possesses a high capacity for proliferation, CD133 expression, self-renewal and differentiation, thus indicating that anaplastic medulloblastoma contains a subpopulation of cancer stem cells as observed in classic medulloblastoma. CONCLUSIONS: 1603-MED provides us with the first in vitro model of anaplastic medulloblastoma that may be suitable for studying both tumour progression and the genetic mechanisms related to therapy resistance, and may lead to the development and testing of chemosensitivity and new therapeutic targets.

Analysis of extended genomic rearrangements in oncological research.

Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific pathological condition are known. Whole-genome methods are used to discover loci bearing structural abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for the analysis of locus-specific structural changes. The first two are based on probe hybridization and include cytogenetics and DNA blotting. The third approach is based on PCR amplification and includes microsatellite or single nucleotide polymorphism (SNP) genotyping, relative allele quantitation, real-time quantitative PCR, long PCR and multiplex PCR-based methods such as multiplex ligation-dependent probe amplification and the recently developed nonfluorescent multiplex PCR coupled to high-performance liquid chromatography analysis. Whole-genome methods include cytogenetic methods, array-comparative genomic hybridization, SNP array and other sequence-based methods. The goal of the present review is to provide an overview of the main features and advantages and limitations of methods for the screening of structural genomic abnormalities relevant to oncological research.

High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability.

Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has been greatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence gene rearrangements not detectable by standard screening methods. However, no criteria for selection of cases to be submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection of familial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2 conventional mutation screening. One hundred and seventy-seven probands were investigated for germline BRCA1/2 mutations after assessment of genetic risk using BRCAPro. Probands were classified as BRCAPro positive (n = 67) when the carrier probability (CP) was >10% and as BRCAPro negative (n = 110), when the CP was <10%. Conventional mutational analyses of the BRCA1/2 genes and, in one case, of p53 identified 22 pathogenetic germline mutations, 12 in BRCA1, 9 in BRCA2 and 1 in p53, in 22/177 (12.4%) probands. All the mutations except one were detected in BRCAPro-positive patients. In the 46 BRCAPro-positive cases that resulted negative by BRCA1/2 mutation, screening analysis of rearrangements within BRCA1/2 by MLPA was carried out. Three patients with a very high CP showed BRCA1 deletions, consisting of deletions of exons 1-2 in two probands and of exon 24 in the third proband. In one case, the exons 1-2 deletion was shown to cosegregate with disease in the family. No BRCA2 rearrangements were detected, but one patient showed the 1100delC of the CHEK2 gene, whose probe is present in the BRCA2 kit. In our series, the highest carrier detection rate of mutation screening plus MLPA analysis (52.3%) was in patients with a BRCAPro CP >50%.

Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin.

BACKGROUND: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. PATIENTS AND METHODS: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The frequency and the spectrum of K-ras mutations were compared with those observed in a series of colorectal cancer patients from Italy. RESULTS: K-ras mutations were observed in 68/182 (37.4%) cases. Mutation frequencies were similar in HNPCC-associated, sporadic MSI-H and sporadic microsatellite-stable (MSS) tumors. However, the G13D substitution was more frequent in HNPCC (3/4, 75%) and sporadic MSI-H (7/11, 63.6%) tumors compared to sporadic MSS tumors (11/53, 20.4%) (P <0.01). Comparison of mutations in the two series from Iran and Italy showed a significantly higher frequency of G13D among Italian patients. CONCLUSIONS: While the frequency of K-ras mutations could be similar, the mutational spectrum could be differentially influenced by genetic and environmental factors.

Evolving role of myeloablative chemotherapy in the treatment of childhood brain tumours.

Primary brain tumours, a heterogeneous group of cancer that constitute the second most common cancer in childhood, were historically treated with neurosurgical resection and radiation therapy. Chemotherapy has proven to be beneficial for some histological types, which has since led to exploration of the role of high-dose chemotherapy and haematopoietic stem cell rescue. Patients with high-grade glial tumours, primitive neuroectodermal tumours and high-risk medulloblastoma usually fare poorly. The indicators of bad prognosis are metastatic status, extent of resection and age. Children <3 years at diagnosis carry worse prognosis. Rare cancers such as ependymoblastoma, atypical teratoid rhabdoid tumour and choroid plexus carcinoma have a dismal prognosis regardless of the above-mentioned indicators. The use of myeloablative therapy (MAT) has been investigated to improve the rate of long-term DFS, as well as to reduce and delay in the youngest children the use of the craniospinal irradiation associated with unacceptable late effects. We will overview the literature regarding patients with 'good and uncertain indications' to MAT. Ependymoma and brain stem tumours, for which the available data discourage the use of MAT, are excluded. Finally, we will summarize a single Institution experience (Giannina Gaslini Children's Hospital, Genoa) with MAT in the period 1997-2003.

Currarino syndrome: proposal of a diagnostic and therapeutic protocol.

BACKGROUND/PURPOSE: The Currarino syndrome (CS) is a peculiar form of caudal regression syndrome (CRS) characterized by the association of hemisacrum, anorectal malformation (ARM), and presacral mass. The authors analyzed retrospectively their series, and they propose a multidisciplinary diagnostic and therapuetic protocol that until now has not been introduced. METHODS: A series of 6 patients with CS is presented. Five of them were treated initially in other centers. None of them had an early diagnosis. All presented associated anomalies; in 50%, Hirschsprung's disease (HD) and other dysganglionoses were present. One patient died of a presacral ectopic nephroblastoma. RESULTS: Depending on the expressivity, 3 types of CS can be identified, complete, mild, and minimal. Dysganglionoses and HD can be considered part of CS. A multidisciplinary diagnostic and therapeutic protocol is presented. Main points are sacrum x-Ray, molecular genetic diagnosis, radiologic evaluation of every member of CS families, magnetic resonance (MR) evaluation of patient spine and pelvis, suction rectal biopsies, and search for associated anomalies. CONCLUSIONS: This protocol could give a valid contribution to the treatment of CS, allowing an early diagnosis and proposing a rational timing of multidisciplinary surgical procedures. Early diagnosis and treatment are essential to avoid morbidity and mortality from an undiagnosed presacral mass.