Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment.
To provide unified guidelines for the treatment of IH with propranolol.
This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting.
The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment.
These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.

The majority of thoracic aortic aneurysms (TAA) in the pediatric population are due to post repair etiology (iatrogenic). Although rare, underlying inheritable disease and congenital cardiac anomalies represent the most common non-iatrogenic cause of TAA among patients in this age group (1-21 years of age). Herein, we present a case series of 9aortic aneurysms with varying underlying etiology. We discuss the molecular genetic basis of these syndromes in conjunction with the radiological findings and histological description utilizing the newly published consensus criteria article.

BACKGROUND: Bridging genotype and phenotype is a fundamental biomedical challenge that underlies more effective target discovery and patient-tailored therapy. Approaches that can flexibly and intuitively, integrate known gene-phenotype associations in the context of molecular signaling networks are vital to effectively prioritize and biologically interpret genes underlying disease traits of interest.
RESULTS: We describe Phenotype Consensus Analysis (PCAN); a method to assess the consensus semantic similarity of phenotypes in a candidate gene\'s signaling neighborhood. We demonstrate that significant phenotype consensus (p < 0.05) is observable for ~67% of 4,549 OMIM disease-gene associations, using a combination of high quality String interactions + Metabase pathways and use Joubert Syndrome to demonstrate the ease with which a significant result can be interrogated to highlight discriminatory traits linked to mechanistically related genes.
CONCLUSIONS: We advocate phenotype consensus as an intuitive and versatile method to aid disease-gene association, which naturally lends itself to the mechanistic deconvolution of diverse phenotypes. We provide PCAN to the community as an R package ( http://bioconductor.org/packages/PCAN/ ) to allow flexible configuration, extension and standalone use or integration to supplement existing gene prioritization workflows.

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OBJECTIVE: A subgroup of patients with infantile hemangiomas have associated structural anomalies of the brain, cerebral vasculature, eyes, sternum, and/or aorta in the neurocutaneous disorder known as PHACE syndrome. The diagnosis has been broadly inclusive by using a case definition of a facial hemangioma plus >or=1 extracutaneous features, leading to numerous reports of potential associated disease features, many of uncertain significance. This consensus statement was thus developed to establish diagnostic criteria for PHACE syndrome.
METHODS: A multidisciplinary group of specialists with expertise in PHACE syndrome drafted initial diagnostic criteria on the basis of review of published, peer-reviewed medical literature and clinical experience. The group then convened in both executive and general sessions during the PHACE Syndrome Research Conference held in November 2008 for discussion and used a consensus method. All conflicting recommendations were subsequently reconciled via electronic communication and teleconferencing.
RESULTS: These criteria were stratified into 2 categories: (1) PHACE syndrome or (2) possible PHACE syndrome. Major and minor criteria were determined for the following organ systems: cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline. Definite PHACE requires the presence of a characteristic segmental hemangioma or hemangioma >5 cm on the face or scalp plus 1 major criterion or 2 minor criteria. Possible PHACE requires the presence of a hemangioma >5 cm on the face or scalp plus 1 minor criterion. The group recognized that it may be possible to have PHACE syndrome with a hemangioma affecting the neck, chest, or arm only or no cutaneous hemangioma at all. In such cases, fulfillment of additional required criteria would also lead to a possible PHACE diagnosis.
CONCLUSIONS: These criteria represent current knowledge and are expected to enhance future assessments of PHACE syndrome. It is understood that modifications are to be expected over time to incorporate new research findings.

Previous mutations associated with lecithin:cholesteryl acyltransferase (LCAT) deficiency syndromes have been identified in the coding regions of the LCAT gene. However, recently, an intron mutation was found in a family in which three sisters presented with fish-eye disease (FED). The probands were shown to be heterozygotes for a mutation in intron 4. The respective T-->C nucleotide substitution, 22 bases upstream of the 3\'-splice site, causes a null allele as the result of complete intron retention. Since the natural mutation occurs in a putative branchpoint consensus sequence of the intron, it was hypothesized that the point mutation may disrupt the splicing of the pre-mRNA. To further study the functional significance of the above thymine residue in the branchpoint sequence, we introduced other nucleotides at this position, i.e., LCAT Int-4 MUT-1 (T-->G) and LCAT Int-4 MUT-2 (T-->A). After stable transfection of the mutated pNUT-LCAT minigenes into BHK cells, we could detect neither LCAT activity nor LCAT protein in the culture medium of the pNUT-LCAT Int-4 MUT-1 and pNUT-LCAT Int-4 MUT-2 cell lines, as was previously described for the natural mutation. To determine the effects of the introduced mutations on pre-mRNA splicing, total RNA from transfected BHK cells was used for RT-PCR analysis. All BHK cell lines were shown to transcribe the integrated LCAT minigenes. However, the sizes of these LCAT messengers indicated that intron 4 was retained in the pNUT-LCAT Int-4 MUT-1 and pNUT-LCAT Int-4 MUT-2 cell lines. Subsequent sequence analysis of the RT-PCR products demonstrated that the unspliced intronic sequences contained the introduced mutations. In conclusion, the observed retention of intron 4 of the LCAT gene is the result of the specific loss of a thymine residue two bases upstream of the branchpoint adenosine residue in the putative branchpoint consensus sequence. The results confirm that a single base change in the branchpoint consensus sequence of an intron can cause human disease although this sequence is poorly conserved in mammals.