Growth patterns and outcomes of growth hormone therapy in patients with acrodysostosis.

INTRODUCTION: Severe short stature is a feature of acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations). METHODS: We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5. RESULTS: We included 20 and 17 individuals with iPPSD4 and iPPSD5, respectively. The rhGH-treated iPPSD4 patients (n = 9) were smaller at birth than those who did not receive rhGH (median - 2.2 SDS vs. - 1.7 SDS); they showed a trend to catch-up growth during rhGH therapy (median 0.5 SDS in the first year). The rhGH-treated patients (n = 5) reached a better final height compared to those who did not receive rhGH (n = 4) (median - 2.8 SDS vs. - 3.9 SDS), suggesting that rhGH is efficient to increase height in those patients. The difference in target height to final height ranged between 1.6 and 3.0 SDS for iPPSD4 not treated with rhGH (n = 4), 2.1-2.8 SDS for rhGH-treated iPPSD4 (n = 5), 0.6-5.5 SDS for iPPSD5 not treated with rhGH (n = 5) and 2.5-3.1 for rhGH-treated iPPSD5 (n = 2). CONCLUSION: Final height may be positively influenced by rhGH in patients with acrodysostosis/iPPSD. Our rhGH-treated cohort started therapy relatively late, which might explain, at least in part, the limited effect of rhGH on height.

The impact of a computerized physician order entry system on medical errors with antineoplastic drugs 5 years after its implementation.

WHAT IS KNOWN AND OBJECTIVE: Computerized physician order entry (CPOE) systems reduce medical errors (MEs). Nevertheless, a CPOE system may also lead to new types of errors, especially when it is first implemented. The objectives of this study were to determine the impact of a CPOE on the number of MEs and to identify the types of MEs in prescriptions issued by the Haematology Department 5 years after the implementation of the CPOE system. METHODS: We conducted a prospective analytical study on the implementation of a CPOE system at the Pharmacy Department of the Hospital Ramon y Cajal (Madrid, Spain). The study comprised three phases: a pre-implementation phase, an implementation phase conducted in the Haematology Department and a post-implementation phase, which was conducted 5 years after the implementation of the CPOE system. One hundred and fifty prescriptions per pre- and post-implementation phase were consecutively included in the study. A previously described classification scheme was used to detect and classify MEs. RESULTS AND DISCUSSION: The implementation of a CPOE system was associated with a large reduction in MEs. One hundred and fourteen patients (pre-implementation phase) were compared to 82 patients (post-implementation phase). The total number of MEs per 100 patients decreased from 236·8 (95% CI: 212·1-261·3) to 10·9 (95% CI: 5·8-19·6), with an absolute risk reduction of 36·2 (95% CI: 32·6-39·9). The percentage of prescriptions with an ME decreased from 37·5% to 1·2% (P < 0.001). In the pre-implementation phase, the drugs most frequently associated with MEs were rituximab (35·9%), cyclophosphamide (13%) and methotrexate (7%). In the post-implementation phase, 44·4% of prescription errors involved methotrexate. Five years after the implementation of the CPOE system, the majority of MEs were eliminated, the number of remaining errors (quantity, concentration and ambiguous prescription errors) decreased, and no new types of ME were detected. WHAT IS NEW AND CONCLUSION: The CPOE system almost completely eliminated MEs with antineoplastic drugs in the Haematology Department. No new types of MEs were observed once physicians had become accustomed to using the system. However, some MEs were not eliminated. Constant diligence is needed to analyse and evaluate MEs associated with the CPOE system and their causes, such that the limitations of CPOE can be identified and overcome and the medication-use process associated with antineoplastic agents improved.

Expert consensus to optimize the treatment of elderly patients with luminal metastatic breast cancer.

Most patients diagnosed with luminal metastatic breast cancer (MBC) who are seen in oncology consultations are elderly. MBC in elderly patients is characterized by a higher percentage of hormone receptor (HR) expression and a lower expression of human epidermal growth factor receptor 2 (HER2). The decision regarding which treatment to administer to these patients is complex due to the lack of solid evidence to support the decision-making process. The objective of this paper is to review the scientific evidence on the treatment of elderly patients with luminal MBC. For this purpose, the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Breast Cancer Research Group (GEICAM) and the SOLTI Group appointed a group of experts who have worked together to establish consensus recommendations to optimize the treatment of this population. It was concluded that the chronological age of the patient alone should not guide therapeutic decisions and that a Comprehensive Geriatric Assessment (CGA) should be performed whenever possible before establishing treatment. Treatment selection for the elderly population should consider the patient's baseline status, the expected benefit and toxicity of each treatment, and the impact of treatment toxicity on the patient's quality of life and functionality.

Surface-guided radiation therapy for breast cancer: more precise positioning.

INTRODUCTION: Hypofractionated radiation therapy for breast cancer requires highly precise delivery through the use of image-guided radiotherapy (IGRT). Surface-guided radiation therapy (SGRT) is being increasingly used for patient positioning in breast radiotherapy. We aimed to assess the role of SGRT for verification of breast radiotherapy and the tumour bed. MATERIALS AND METHODS: Prospective study of 252 patients with early stage breast cancer. A total of 1170 determinations of daily positioning were performed. Breast surface positioning was determined with SGRT (AlignRT) and correlated with the surgical clips in the tumour bed, verified by IGRT (ExacTrac). RESULTS: SGRT improved surface matching by a mean of 5.3 points compared to conventional skin markers (98.0 vs. 92.7), a statistically significant difference (p < 0.01, Wilcoxon Test). For surface matching values > 95%, ≥ 3 clips coincided in 99.7% of the determinations and all markers coincided in 92.5%. For surface matching rates > 90%, the location of ≥ 3 clips coincided in 99.55% of determinations. CONCLUSIONS: SGRT improves patient positioning accuracy compared to skin markers. Optimal breast SGRT can accurately verify the localisation of the tumour bed, ensuring matching with ≥ 3 surgical clips. SGRT can eliminate unwanted radiation from IGRT verification systems.

Crohn's disease and Sweet's syndrome: an uncommon association.

Sweet's syndrome or acute febrile neutrophilic dermatosis (SS) is characterized by the sudden onset of painful erythematous lesions (papules, nodules, and plaques) together with fever and neutrophilia. The lesions are typically located on hands, arms, upper trunk, neck and face, showing an asymmetric distribution. Acute phase reactants are usually elevated and dermal infiltration of neutrophils without vasculitis is seen on skin biopsies. It is considered as a marker of systemic disease in over half of the cases, and is associated with infections, inflammatory bowel disease, autoimmune connective tissue disorders and various neoplasias. Its association with Crohn's disease (CD) is unusual and it appears mainly in association with colonic involvement. Fewer than 50 cases have been published in the medical literature since its first description in 1964, some concurrent with the first episode of CD. We present two patients with Crohn's disease and Sweet's syndrome diagnosed in our department at the time of CD diagnosis, as well as their response to treatment, subsequent course of the disease, and a review of the scientific literature.

Clinical significance of epithelial-mesenchymal transition-related markers expression in the micrometastatic sentinel lymph node of NSCLC.

OBJECTIVES: Metastatic lymph node affectation is the main prognostic factor in localised lung cancer. However, the pathological study of lymph nodes reveals tumour relapse for 20% of patients after oncological curative surgery. Recently, EMT (epithelial-mesenchymal transition) has been established as one of the main factors related to lymphatic dissemination and metastasis. This study evaluated the prognostic value of EMT-related gene expression in micrometastatic sentinel lymph nodes (SLN) of non-small cell lung cancer (NSCLC) patients. METHODS: The presence of genes CDH1, CDH2, VIM, TWIST1, SNAI1, SNAI2, ZEB1, and ZEB2 in mRNA was analysed in tumours and in the SLN of NSCLC patients for whom surgery was planned for treatment. The significant association between the expression level of EMT-related markers and patients' clinicopathological characteristics and relapse was assessed. RESULTS: Of the 96 patients, 56 (58.33%) presented molecular micrometastasis in SLN, which showed higher CDH1, CDH2, and VIM expressions than non-micrometastatic ones. An association linking a low CDH1/CDH2 ratio in SLN with molecular micrometastasis, adenocarcinoma, and non-smoking patients was found. The multivariate Cox regression analysis proved the prognostic accuracy of the CDH1/CDH2 ratio in SLN. CONCLUSIONS: The molecular EMT status of SLN could be used as an independent prognosis predictor in early stage NSLCL patients, and as a new tool to better stratify and predict patient outcomes.

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

FDTD assessment of human exposure to electromagnetic fields from WiFi and bluetooth devices in some operating situations.

In this work, the numerical dosimetry in human exposure to the electromagnetic fields from antennas of wireless devices, such as those of wireless local area networks (WLAN) access points or phone and computer peripherals with Bluetooth antennas, is analyzed with the objective of assessing guidelines compliance. Several geometrical configurations are considered to simulate possible exposure situations of a person to the fields from WLAN or Bluetooth antennas operating at 2400 MHz. The exposure to radiation from two sources of different frequencies when using a 1800 MHz GSM mobile phone connected via Bluetooth with a hands-free car kit is also considered. The finite-difference time-domain (FDTD) method is used to calculate electric and magnetic field values in the vicinity of the antennas and specific absorption rates (SAR) in a high-resolution model of the human head and torso, to be compared with the limits from the guidelines (reference levels and basic restrictions, respectively). Results show that the exposure levels in worst-case situations studied are lower than those obtained when analyzing the exposure to mobile phones, as could be expected because of the low power of the signals and the distance between the human and the antennas, with both field and SAR values being far below the limits established by the guidelines, even when considering the combined exposure to both a GSM and a Bluetooth antenna.

[Effectiveness, safety, and tolerability of intragastric balloon in association with low-calorie diet for the treatment of obese patients]. / Efectividad, seguridad y tolerancia del balón intragástrico asociado a una dieta hipocalórica para la reducción de peso en pacientes obesos.

INTRODUCTION: the endoscopic placement of an intragastric balloon (IGB) in association with a low-calorie diet is an option for the treatment of obesity. The aim of the present study was to evaluate its effectiveness, safety, and tolerance. MATERIAL AND METHODS: thirty-eight patients with no contraindications for IGB were included in this prospective study from March 2004 to January 2007. Balloon removal was performed 6 months later. Weight and body mass index (BMI) were evaluated after IGB removal and at 6 months and 1 year thereafter. Tolerance and complications during treatment were evaluated. Patients filled out a questionnaire to evaluate their subjective perception of treatment. RESULTS: mean weight loss after 6 months on balloon treatment was 14.10 kg (0-46), and mean BMI reduction was 5.23 kg/m2 (0-18). At 12 months after balloon removal 48.4% of patients maintained their weight loss or kept loosing weight. Most common early symptoms included nausea (71.1%) and vomiting (57.9%) with a good response to symptomatic treatment. Complications were seen in 7 patients (18.4%): digestive intolerance in 4 patients, with early removal in 3 of them; moderate esophagitis in 2 patients; and gastric perforation complicated with septic shock and death in 1 patient. CONCLUSIONS: 1. IGB in association with low-calorie diet is an effective, safe, and well tolerated treatment for morbid obese patients.2. Almost half of patients maintained their weight loss after one year from balloon removal.

Failure modes and effects analysis of total skin electron irradiation technique.

PURPOSE: Total skin electron irradiation (TSEI) is a radiotherapy technique which consists of an homogeneous body surface irradiation by electrons. This treatment requires very strict technical and dosimetric conditions, requiring the implementation of multiple controls. Recently, the Task Group 100 report of the AAPM has recommended adapting the quality assurance program of the facility to the risks of their processes. MATERIALS AND METHODS: A multidisciplinary team evaluated the potential failure modes (FMs) of every process step, regardless of the management tools applied in the installation. For every FM, occurrence (O), severity (S) and detectability (D) by consensus was evaluated, which resulted in the risk priority number (RPN), which permitted the ranking of the FMs. Subsequently, all the management tools used, related to the TSEI process, were examined and the FMs were reevaluated, to analyze the effectiveness of these tools and to propose new management tools to cover the greater risk FMs. RESULTS: 361 FMs were identified, 103 of which had RPN ≥80, initially, and 41 had S ≥ 8. Taking this into account the quality management tools FMs were reevaluated and only 30 FMs had RPN ≥80. The study of these 30 FMs emphasized that the FMs that involved greater risk were related to the diffuser screen placement and the patient's position during treatment. CONCLUSIONS: The quality assurance program of the facility has been adapted to the risk of this treatment process, following the guidelines proposed by the TG-100. However, clinical experience continually reveals new FMs, so the need for periodic risk analysis is required.

A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1). METHODS: A genome-wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families. RESULTS: Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD-unit support interval. CONCLUSIONS: We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.

Topography of the sentinel node according to the affected lobe in lung cancer.

PURPOSE: The objective of this study is to describe the anatomic location of the sentinel lymph node (SLN) of patients with lung carcinoma and to analyze its relationship with the characteristics of the tumor. PATIENTS AND METHODS: 98 Stage I lung cancer patients were included in the study. SLN was marked just after performing the thoracotomy by injecting peritumorally 0.25 mCi of nanocolloid of albumin (Nanocol1) labeled with Tc-99 m in 0.3 ml, and later, it was resected. For SLN micrometastasis analysis, CEACAM5, BPIFA1, and CK7 gene expression at mRNA level was studied. Possible relation between tumor characteristics and SLN location was analyzed. RESULTS: While most of the SLN were located in hilar area, we find a significantly higher number of SLN located in mediastinal stations when the lesion is in the left upper lobe (LUL). This difference disappears in the group of SLN with a positive result in the micrometastasis study. Regarding tumor size, squamous tumors and tumors located in the left lower lobe (LLL) were found significantly larger. CONCLUSION: The location of the SLN in patients with stage I lung cancer is predominantly hilar, being less consistent in the left hemithorax. The tumor size or histological type is not variables that affect this distribution. The distribution of SLNs with a positive result in the analysis of micrometastasis suggests further spread to the hilar areas when the lesion is in the LUL and to the mediastinal zones when it is in the LLL.

Small supernumerary marker chromosomes--progress towards a genotype-phenotype correlation.

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they are too small to be characterized for their chromosomal origin by traditional banding techniques, but require molecular cytogenetic techniques for their identification. Apart from the correlation of about one third of the sSMC cases with a specific clinical picture, i.e. the i(18p), der(22), i(12p) (Pallister Killian syndrome) and inv dup(22) (cat-eye) syndromes, most of the remaining sSMC have not yet been correlated with clinical syndromes. Recently, we reviewed the available >1600 sSMC cases (Liehr T, sSMC homepage: http://mti-n.mti.uni-jena.de/~huwww/MOL_ZYTO/sSMC.htm). A total of 387 cases (including the 45 new cases reported here) have been molecularly cytogenetically characterized with regard to their chromosomal origin, the presence of euchromatin, heterochromatin and satellite material. Based on analysis of these cases we present the first draft of a basic genotype-phenotype correlation for sSMC for all human chromosomes apart from the chromosomes Y, 10, 11 and 13.

Meat Consumption and Risk of Developing Type 2 Diabetes in the SUN Project: A Highly Educated Middle-Class Population.

BACKGROUND: Meat consumption has been consistently associated with the risk of diabetes in different populations. The aim of our study was to investigate the incidence of type 2 diabetes according to baseline total meat consumption in a longitudinal assessment of a middle-aged Mediterranean population. METHODS: We followed 18,527 participants (mean age: 38 years, 61% women) in the SUN Project, an open-enrolment cohort of a highly educated population of middle-class Spanish graduate students. All participants were initially free of diabetes. Diet was assessed at baseline using a semi-quantitative food frequency questionnaire of 136-items previously validated. Incident diabetes was defined according to the American Diabetes Association's criteria. RESULTS: We identified 146 incident cases of diabetes after a maximum of 14 years of follow-up period (mean: 8.7 years). In the fully adjusted model, the consumption of ≥3 servings/day of all types of meat was significantly associated with a higher risk of diabetes (HR: 1.85; 95% CI: 1.03-3.31; p for trend = 0.031) in comparison with the reference category (<2 servings/day). When we separated processed from non-processed meat, we observed a non-significant higher risk associated with greater consumption of processed meat and a non-significant lower risk associated with non-processed meat consumption (p for trend = 0.123 and 0.487, respectively). No significant difference was found between the two types of meat (p = 0.594). CONCLUSIONS: Our results suggest that meat consumption, especially processed meat, was associated with a higher risk of developing diabetes in our young Mediterranean cohort.

Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer.

INTRODUCTION: Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I. PATIENTS AND METHODS: ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by real-time quantitative RT-PCR in fresh-frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLC patients. Later, significant association between gene expression levels, clinicopathological characteristics and patient's disease-free survival was assessed. RESULTS: We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease-free survival in stage I NSCLC patients. CONCLUSION: Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLC patients.

[Primary prevention and treatment of latent tuberculosis infection with isoniazid: efficacy of a control program, 1997-2002]. / Prevención primaria y tratamiento de la infección tuberculosa latente con isoniacida: eficacia de un programa de control, 1997-2002.

OBJECTIVE: To analyze the efficacy of a specific program for the study and follow up of tuberculosis contacts. To study factors related to low adherence to treatment and to the development of liver toxicity caused by isoniazid. PATIENTS AND METHODS: Between December 1996 and December 2002, we found 458 contacts of 79 cases of pulmonary tuberculosis in patients uninfected by human immunodeficiency virus. The contacts were screened for tuberculosis infection and chemoprophylaxis was prescribed according to the recommendations of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). RESULTS: We identified 3 cases of tuberculosis among the contacts (prevalence 0.8%). Chemoprophylaxis with isoniazid was prescribed for 215 contacts. One hundred sixty-nine (79%) completed the prophylaxis protocol. The rate of adherence to treatment was lower in immigrants than in nonimmigrants (odds ratio, 3.42; 95% confidence interval, 1.03-11.04; P=.02). Forty-three patients (22%) developed liver toxicity during treatment, which had to be suspended in 3 cases. Duration of chemoprophylaxis was the only independent variable associated with liver toxicity (odds ratio, 3.80; 95% confidence interval, 1.10-13.13; P=.03). CONCLUSIONS: Our study demonstrates the effectiveness of a specific program of study and follow up of tuberculosis contacts. Immigrants require tailored strategies to improve their adherence to the program. The duration of chemo-prophylaxis plays an important role in the development of liver toxicity.

Duplication of hands and feet, multiple joint dislocations, absence of corpus callosum and hypsarrhythmia: acrocallosal syndrome?

We describe a 14-month-old female infant with absence of corpus callosum, atrophy of optic nerve, peculiar face, complex polydactyly, multiple joint abnormalities, and femoral shortness. The similarities to and differences from previously reported cases of this kind suggest that our patient has a new type of acrocallosal syndrome.

Epidemiological analysis of multi-site closure failure of neural tube in humans.

Van Allen et al. [Am J Med Genet 47:723-743, 1993] proposed that there is multi-site initiation of neural tube closure in humans, and that neural tube defects (NTD) represent the failure of one or more of 5 closure sites. We have studied from an epidemiologic perspective 774 liveborn infants with NTD by site of lesion following the multi-site classification proposed by Van Allen et al. [1993]. As predicted by these authors, we could classify all the cases with NTD by the multisite closure model. We have also estimated the prevalence of each failure closure site. This analysis indicates that not all the sites are affected with similar frequency.

Dynamic mosaicism involving an unstable supernumerary der(22) chromosome in cat eye syndrome.

We have studied a girl, her sister and her mother who had a supernumerary marker chromosome in mosaicism. The marker was studied by cytogenetic methods and non-isotopic in situ hybridization with the single D22S9 DNA probe which maps to 22q11. The supernumerary chromosome was derived from a chromosome 22 and it did not present the same morphology in all the cells. At least 5 distinct types of the marker chromosome were detected and some of them were probably derived from each other (dynamic mosaicism). The proposita had an MCA pattern consistent with mild cat eye syndrome, while her sister and her mother had some of the manifestations described in this syndrome. A specific correlation could be established between phenotype and karyotype.

Ring chromosome 7 and sacral agenesis.

A ring chromosome 7 was found in a 19-month-old girl with microcephaly, growth and developmental delay, multiple angiomas, and partial sacral agenesis. Absent sacrum is a frequent finding in patients with 7q terminal deletions; in fact, genes involved in the sacral agenesis are localized in 7q36. However, this anomaly was not described previously in patients with a ring chromosome 7. High resolution G-banding chromosome and fluorescence in situ hybridization (FISH) demonstrated that our patient lost this region during ring formation.