Complex mode of inheritance in holoprosencephaly revealed by whole exome sequencing.

Holoprosencephaly (HPE) is the most common congenital cerebral malformation, characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been associated with HPE and are often inherited from an unaffected parent, underlying complex genetic bases. It is now emerging that HPE may result from a combination of multiple genetic events, rather than from a single heterozygous mutation. To explore this hypothesis, we undertook whole exome sequencing and targeted high-throughput sequencing approaches to identify mutations in HPE subjects. Here, we report two HPE families in which two mutations are implicated in the disease. In the first family presenting two foetuses with alobar and semi-lobar HPE, we found mutations in two genes involved in HPE, SHH and DISP1, inherited respectively from the father and the mother. The second reported case is a family with a 9-year-old girl presenting lobar HPE, harbouring two compound heterozygous mutations in DISP1. Together, these cases of digenic inheritance and autosomal recessive HPE suggest that in some families, several genetic events are necessary to cause HPE. This study highlights the complexity of HPE inheritance and has to be taken into account by clinicians to improve HPE genetic counselling.

Arterial spin labeling in clinical pediatric imaging.

Arterial spin labeling (ASL) perfusion-weighted magnetic resonance imaging is the only approach that enables direct and non-invasive quantitative measurement of cerebral blood flow in the brain regions without administration of contrast material and without radiation. ASL is thus a promising perfusion imaging method for assessing cerebral blood flow in the pediatric population. Concerning newborns, there are current limitations because of their smaller brain size and lower brain perfusion. This article reviews and illustrates the use of ASL in pediatric clinical practice and discusses emerging cerebral perfusion imaging applications for children due to the highly convenient implementation of the ASL sequence.

Umbilical vein varix: Importance of ante- and post-natal monitoring by ultrasound.

Foetal intra-abdominal umbilical vein varix is rare. Colour Doppler ultrasonography helps distinguish this vascular anomaly. A detailed anatomic scan must be performed to exclude associated anomalies: forms associated with additional complications are found in 29 to 35% of the cases. Intra-uterine foetal demise (IUFD) is a complication of umbilical vein varix. However, recent studies are more reassuring. When foetal intra-abdominal umbilical vein varix is isolated, there is no reason to change the management of the pregnancy. Foetal sonographic follow-up is recommended, focusing on an increase in the size of the varix and the appearance of a clot. A particular clinical form, connecting the umbilicus to the extra-hepatic portal vein should be known, because of a high risk of thrombosis. On the basis of this finding, postnatal monitoring by ultrasound is necessary.

Pubo-femoral distance: an easy sonographic screening test to avoid late diagnosis of developmental dysplasia of the hip.

OBJECTIVES: To propose an easy and reproducible sonographic screening test able to avoid late presentation of developmental dysplasia of the hip (DDH). METHODS: The pubo-femoral distance (PFD) cut-off point was determined on 980 infants who underwent ultrasonography of the hips in comparison with the final diagnosis, based on clinical, ultrasound data and follow-up. PFD reproducibility was tested on 52 hips by both an experienced and an inexperienced radiologist. After teaching this screening method to general radiologists, its impact was evaluated by analysing the rate of late diagnosis in an entire administrative area. RESULTS: An abnormal PFD threshold above 6 mm gave a sensitivity of 97.4 % for the diagnosis of DDH (271 hips) and a specificity of 84 %. Sensitivity increased to 100 % when taking into consideration children of 1 month or older. The PFD measurement stayed reproducible even in inexperienced hands (k = 0.795). For 3 years, following the extension of screening to all female infants, there was no late diagnosis of DDH in girls in amongst a catchment area of 1 million inhabitants. CONCLUSIONS: PFD measurement with a threshold for abnormality of 6 mm at the age of 1 month, without asymmetry above 1.5 mm, could eradicate DDH late diagnosis.

Idiopathic club foot treated with the Ponseti method. Clinical and sonographic evaluation of Achilles tendon tenotomy. A review of 221 club feet.

The Ponseti method applied to treating idiopathic club foot consists in placing successive corrective casts, possibly an Achilles tendon tenotomy, then derotation braces, a method that has proven its efficacy. This study compared 221 cases of club foot treated with this method between 2002 and 2007 divided into two groups, based on whether or not Achilles tendon tenotomy was performed. Assessment was both clinical and sonographic. We observed clear improvement of the results in the group that underwent Achilles tendon tenotomy and a significant difference in the rate of secondary surgery. The sonographic evaluation also showed improvement of the morphological results. We now systematically propose Achilles tendon tenotomy however severe club foot may be.

A revised classification of the temporal branches of the posterior cerebral artery.

PURPOSE: Understanding the vascular variability of the inferior temporal occipital regions is essential for microsurgical approaches to this cerebral zone. To this end, we carried out a microanatomical study of the inferior temporal cortical branches of the posterior cerebral artery (PCA) in order to define their vascularisation territories. METHODS: We studied 40 cerebral hemispheres (20 brains) under an operating microscope. Three brains were fixed in Winkler's solution with latex arterial perfusion and the other 17 brains were fixed in formaldehyde solution. RESULTS: Our revised classification was based on the following findings. First, the anterior hippocampal artery was always associated with the anterior temporal artery, with the two sharing the vascularisation of the anterior part of the inferior temporal lobe. Second, the middle hippocampal and middle temporal arteries were never present together. Third, the presence of an anterior temporal artery always involved the presence of a posterior temporal artery. Hence, we classified the temporal branches of the PCA into three new patterns. The first pattern includes the anterior and posterior temporal arteries without the anterior hippocampal artery. The second pattern includes the anterior hippocampal artery and anterior and posterior temporal arteries. The third pattern includes the common temporal artery. The first pattern was found most frequently (n = 23, 57.5%), followed by the second (n = 9, 22.5%) and third patterns (n = 8, 20%). CONCLUSIONS: We propose a revised classification of the inferior temporal branches of the PCA that takes into account their vascularisation territories.

Irreducible developmental dysplasia of the hip due to acetabular roof cartilage hypertrophy. Diagnostic sonography in 15 hips.

INTRODUCTION: Irreducible developmental dysplasia of the hip (DDH) in newborns is a rare entity. The different obstacles preventing reduction have been described in the literature. HYPOTHESIS: A clinical form of DDH with hypertrophy of the cartilage of the acetabular roof (acetabular bulge) can be reliably identified on ultrasound and should probably be defined as a separate entity. MATERIALS AND METHODS: For the first time, the authors report their experience, a review of the literature and the radiographic description (ultrasound, arthrography MRI) of irreducible neonatal DDH due to hypertrophy of the cartilage of the acetabular roof (acetabular bulge) in 12 infants (15 hips). RESULTS: Neonatal sonography seems to be sufficient to identify this specific clinical entity without any additional work-up. This sonographic sign could help determine the therapeutic strategy earlier in this severe and complex form of DDH.

[Developmental dysplasia of the hip]. / Luxation congénitale de hanche chez l'enfant.

At one month, the acetabular depth from a standard lateral coronal section is 4.6 ± 1.0mm. The correlation between experienced and junior radiologists is high (kappa 0.795). A treshhold of 6mm with a Δ (difference between right and left) less than 1.5mm provides a sensitivity of 100% for the detection of DDH at one month. Universal US screening at one month of all high-risk infants in 2009 resulted in a reduction of delayed diagnosis of DDH (zero girls, two boys) in Ille-et-Vilaine due to continuous medical education of general radiologists.

[Analytic study of hopes and perceptions of second-year medical school students during gross anatomy laboratory cessions]. / Enquête sur les attentes et appréhensions des étudiants de deuxième année de médecine au cours des séances de dissections.

INTRODUCTION: Using an anonymous questionnaire, this study aimed to assess hopes and perceptions of second-year medical school students faced to gross anatomy dissections and to appreciate the status of dissection within the others anatomical teaching tools. MATERIALS AND METHODS: The questionnaire was distributed among 210 second-year medical students during gross anatomy dissections. The first part of the questionnaire aimed to assess perceptions of students before dissections while the second part aimed to position dissection in their anatomical teaching cursus. RESULTS: Within the 210 students participating to the study, 70 (45%) had not seen a dead human body before the laboratory cession. The main stressful factors were technical difficulties encountered during dissection more than embarrassment in front of the cadaver. The level of stress was significantly higher in female students. Hand, neck and gluteal regions were the most stressful regions reported by students. Students considered that gross anatomy dissection was a key ritual experience crucial for their formation that should not be only proposed to senior practitioners. CONCLUSION: This study illustrates the invariable interest of medical students for gross anatomy laboratory cessions that permit a first technical experience, faced to the death.

[Electronic imaging with photo-realistic rendering for neuroanatomy teaching. Methods and preliminary results]. / Imagerie électronique en rendu photo-réaliste pour l'enseignement de la Neuro-anatomie. Méthodes et résultats.

Advances in software, networking, and imaging technology provide a unique opportunity for developing information systems in anatomy that can deliver relevant knowledge to the clinicians, researchers, educators, and students. Recent software tools initially produced for graphic imaging are now available in the medical graphic design field. The authors describe an original method they used to create electronic images of the central nervous system and its coverings with photo-realistic rendering. They present preliminary results and discuss the potential of this new technique as a teaching tool for neuroanatomy.

Anatomic bases for the compression and neurolysis of the deep branch of the radial nerve in the radial tunnel.

The anatomy of the radial tunnel was studied on twenty-five elbow preparations. We noted five different elements that could affect the deep branch of the radial nerve in the radial tunnel and cause an entrapment syndrome: a capsule-tendon-aponeurotic complex on the anterior aspect of both the humeroradial joint and the radial head, the vascular arcade formed by the radial recurrent a, and its branches, the arcade formed by the medial edge of extensor carpi radialis brevis muscle, and the superior and inferior arcades of the superficial layer of the supinator muscle. These results are compared with recent anatomical and clinical data, and the relevance of a surgical approach between the extensor carpi radialis brevis and longus muscles is discussed.

Unusual origin of the ophthalmic artery and occlusion of the central retinal artery.

Any variations in the origin of the ophthalmic a. are uncommon and well-explained by the comparative anatomy and human embryology. A unique case is reported of an ophthalmic a. arising from the middle meningeal a. associated with an occlusion of the central retinal a. Embryologic variations which can give such an unusual origin are discussed. Although this association may be fortuitous, we consider that an unusual origin of the ophthalmic a. could be a further factor for an occlusion of the central retinal a.

Microsurgical anatomy of the anterior choroidal artery.

In this study, the authors present the results of 50 dissections of the anterior choroidal a. in man. Fifty cerebral hemispheres were prepared with the classic techniques of preservation and vascular injection. An ectopic origin was observed in 4% of cases. The intracisternal segment of the anterior choroidal a. forms a neurovascular bundle with the optic tract and basal v. Most of its intraparenchymatous branches arise from the cisternal segment, while branches supplying the optic tract, lateral geniculate body and thalamus arise from the intraplexual segment. Constant anastomoses exist with the vertebrobasilar system, specially the postero-lateral choroidal and posterior cerebral aa. We discuss the importance of an adequate knowledge of the anatomy of the anterior choroidal a. and its relations in the surgical approach to arterial aneurysms and arteriovenous malformations of the region.

Anatomical relationships and scapular attachments of the supraspinatus muscle.

Ten anatomical preparations and 15 MRI scans (Magnetic Resonance Imaging) performed on healthy subjects were used to define accurately the lateral attachments and anatomical boundaries of the supraspinatus m. Using 5 frozen specimens sectioned in the plane corresponding to the sagittal oblique MRI plane, it was possible to calculate quantitatively the ratio between the bony contours (O) and muscles (M) of the supraspinous fossa. This ratio was maximal (O/M = 2.4) for the section passing through the plane which included the coracoid process anteriorly and the spine of the scapula posteriorly ("Y" section). Five dissections on unembalmed subjects demonstrated that the postero-lateral origin of supraspinatus m. extended further laterally than classically described. This observation was confirmed in the 15 MRI subjects which showed that the supraspinatus m. may arise as far laterally as the "Y" section on MRI in 53% of cases. A quantitative evaluation of atrophy of the supraspinatus m. using MRI is possible with a knowledge of these two parameters.

[Testicular microlithiasis: ultrasonographic diagnosis and semiologic value]. / Microlithiases testiculaires: diagnostic échographique et valeur sémiologique.

Testicular microlithiasis corresponds to calcifications in the lumen of seminiferous tubules. This rare condition, primarily diagnosed histologically, is usually discovered on scrotal ultrasonography. The characteristic appearance combines multiple microscopic hyperechoic areas disseminated bilaterally throughout the testicular parenchyma. The coexistence of microlithiasis and testicular neoplasms has been described and raises the problem of the therapeutic approach following incidental discovery on scrotal ultrasonography performed for other reasons. The authors report a case of testicular microlithiasis discovered on ultrasonography performed after testicular trauma.

[Extrapulmonary mycobacterial infection with multiple cold abscesses]. / Infection extrapulmonaire à mycobactéries avec abcès froids multiples.

We report one case of extrapulmonary mycobacterial infection, in the absence of HIV infection, singular by a clinical presentation simulating a tumor, associating a bulky intrahepatic mass, an abscess of the psoas, multiple intracerebral lesions, and an obstructive intracardiac mass of the right ventricle, which required a surgical resection. We comment the type of the mycobacterium involved and the hepatic and cardiac localisations, since macronodular hepatic abscesses are rare, and cardiac abcesses, exceptional.

Accuracy of ultrasound diagnosis after blunt testicular trauma.

The aim of this study is to determine the value of ultrasound evaluation for the diagnosis of testis rupture due to blunt scrotal trauma. We reviewed 16 operated cases of blunt scrotal trauma with hematocele, which were evaluated by ultrasound preoperatively. In 2 cases a tunica albuginea rupture was correctly diagnosed by ultrasonography but there were 2 false-positive and 5 false-negative diagnoses of rupture. Systematic exploration of the 16 cases revealed testicular rupture in 7, simple hematocele in 7 and hematocele associated with spermatic cord injury in 2. In 2 cases orchiectomy was necessary. From our experience the accuracy rate of ultrasound evaluation of blunt scrotal trauma was 56%, with a 58% negative predictive value. Considering these results, ultrasound examination of blunt scrotal trauma with hematocele is not sufficiently accurate to eliminate surgical exploration and, therefore, we recommended early surgical exploration as primary therapy in these cases.

[Congenital intrahepatic arterio-portal fistula: diagnostic and therapeutic aspects]. / Fistule artérioporte intrahépatique congénitale: aspects diagnostiques et thérapeutiques.

The authors report the case of a 4 month old child presenting with a congenital arteriovenous fistula of the left hepatic lobe, revealed by a melaena. Doppler ultrasonography and angiography showed a voluminous vascular malformation fed by a left hepatic artery and fistulized in the portal vein. The therapeutical approach was first palliative, by ligature of the left hepatic artery which proved unsuccessful and resulted in re-permeation of the malformation through a right hepatic artery. Two embolization procedures were then attempted, without success. A left hepatectomy was then performed to remove the malformation. The main event of outcome was the secondary occurrence of a portal cavernoma, with persistent splenic segmentary portal hypertension, and oesophageal varicosity. This case report is the occasion for a literature review on congenital arteriovenous fistulae in the portal region, and for a discussion on therapeutical modalities.

[Endoscopic treatment and extracorporeal lithotripsy in chronic calcifying pancreatitis. Preliminary results in 16 patients]. / Traitement endoscopiquie et lithotritie extra-corporelle au cours de la pancréatite chronique calcifiante. Résultats préliminaires chez 16 patients.

UNLABELLED: A new therapeutic approach has been recently proposed in the management of chronic pancreatitis, including pancreatic endoscopic papillotomy and extracorporeal shock wave lithotripsy. The aim of this study was to assess the feasibility and the short--and long-term results of these procedures in a series of 16 patients aged 48.9 +/- 14 years. The indication for endoscopic treatment was pain in 15 cases and steatorrhea in one case. Pancreatic duct abnormalities included main pancreatic duct stenosis with calculi (9 cases), communicating pseudocysts upstream to a ductal stenosis or obstruction by calculi (4 cases), and isolated calculi (4 cases). Clinical response and morphologic parameters were used for analysis. Mean follow-up was 18.6 months (3.5 months to 7 years). RESULTS: a) pancreatic endoscopic papillotomy, stents placement, and extracorporeal shock wave lithotripsy were successfully performed in 15 out of 16 cases, 1 out of 4 cases and 8 out of 8 cases, respectively; b) symptomatic improvement was observed in 11 of 15 patients with painful pancreatitis as relief was complete in 8, and partial in 3 cases. Pain relapse occurred in these latter 3 patients 4, 18 and 48 months after treatment; diabetes mellitus remained unchanged in all cases; c) diameter of the main pancreatic duct and pancreatic calcifications decreased in 8 of 15 cases and in 10 of 15 cases, respectively; pseudocyst disappeared in 2 of 4 cases; clinical improvement was significantly correlated with pancreatic morphology improvement. Clinical relapse was associated with calculi recurrence in every case. No complication was observed. Endoscopic papillotomy and extracorporeal shock wave lithotripsy are feasible in most cases of chronic pancreatitis. Relief of pain is obtained rapidly after treatment and seems to be correlated with the quality of pancreatic drainage.

Relationship between gastric mucosal changes and hemodynamic patterns in alcoholic cirrhosis. A prospective study.

Most gastric mucosal changes in cirrhosis are thought to be related to vasculopathy. The aim of this study was to determine whether there was a relationship between gastric mucosal changes and hemodynamic in cirrhosis. Thirty patients with alcoholic cirrhosis were divided into four groups: no congestive gastropathy (n = 6), mild congestive gastropathy type 1 (discrete mosaic pattern) (n = 9), mild congestive gastropathy type 2 (obvious mosaic pattern) (n = 9), and severe congestive gastropathy (n = 6). The four groups did not significantly differ with respect to clinical and biochemical data, degree of hepatic dysfunction, or endoscopic signs of portal hypertension. A hyperdynamic circulatory syndrome was observed in most patients, but tended to be more pronounced in patients with severe congestive gastropathy and mild congestive gastropathy type 2 as compared to patients with normal mucosa, or mild congestive gastropathy type 1. Systemic vascular resistance was found to be significantly lower in high-grade patients (mild congestive gastropathy type 2 + severe congestive gastropathy, n = 15) as compared with low-grade patients (no congestive gastropathy + mild congestive gastropathy type 1, n = 15) (736 +/- 267 vs 1,046 +/- 403 dyne.s.cm-5, P = 0.02). Neither splanchnic hemodynamics as assessed by the degree of portal hypertension (hepatic venous pressure gradient) and superior mesenteric artery vascular resistance (Doppler measurement of the pulsatility index) catecholamines or glucagon serum levels differed significantly between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)