Rajesh Kannan

Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome

Background Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome. Methods We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies. Results Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspected based on the craniofacial features, despite the absence of corpus callosum anomaly in one and of polydactyly in another. Hallux duplication was absent in 4/5 cases. Conclusions These results show that ACLS has a variable expressivity and can be diagnosed even in the absence of the two major features, namely polydactyly or agenesis or hypoplasia of the corpus callosum. Facial dysmorphism with hypertelorism and prominent forehead in all the cases, as well as vermis dysgenesis with brainstem anomalies (molar tooth sign), strongly indicated the diagnosis. KIF7 should be tested in less typical patients in whom craniofacial features are suggestive of ACLS.

Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis

BackgroundVascular elasticity is crucial for maintaining hemodynamics. Molecular mechanisms involved in human elastogenesis are incompletely understood. We describe a syndrome of lethal arteriopathy associated with a novel,identical mutation in the fibulin 4 gene (FBLN4) in a unique cohort of infants from South India.MethodsClinical characteristics, cardiovascular findings, outcomes and molecular genetics of twenty-two infants from a distinct population subgroup,presenting with characteristic arterial dilatation and tortuosity during the period August 2004 to June 2011 were studied.ResultsPatients (11 males, 11 females) presented at median age of 1.5 months,belonging to unrelated families from identical ethno-geographical background; eight had a history of consanguinity. Cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%),sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%). Genetic studies revealed an identical c.608A > C (p. Asp203Ala) mutation in exon 7 of the FBLN4 gene in all 22 patients, homozygous in 21, and compound heterozygous in one patient with a p. Arg227Cys mutation in the same conserved cbEGF sequence.Homozygosity was lethal (17/21 died, median age 4 months). Isthmic hypoplasia (n = 9) correlated with early death (≤4 months).ConclusionsA lethal, genetic disorder characterized by severe deformation of elastic arteries, was linked to novel mutations in the FBLN4 gene. While describing a hitherto unreported syndrome in this population subgroup, this study emphasizes the critical role of fibulin-4 in human elastogenesis.

Three-dimensional-printed cardiac prototypes aid surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases: Early experience and proof of concept in a resource-limited environment

Introduction: Three-dimensional. (3D) printing is an innovative manufacturing process that allows computer.assisted conversion of 3D imaging data into physical “printouts” Healthcare applications are currently in evolution. Objective: The objective of this study was to explore the feasibility and impact of using patient-specific 3D-printed cardiac prototypes derived from high.resolution medical imaging data. (cardiac magnetic resonance imaging/computed tomography. [MRI/CT]) on surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases. (CHDs). Materials and Methods: Five patients with complex CHD with previously unresolved management decisions were chosen. These included two patients with complex double.outlet right ventricle, two patients with criss-cross atrioventricular connections, and one patient with congenitally corrected transposition of great arteries with pulmonary atresia. Cardiac MRI was done for all patients, cardiac CT for one; specific surgical challenges were identified. Volumetric data were used to generate patient-specific 3D models. All cases were reviewed along with their 3D models, and the impact on surgical decision-making and preoperative planning was assessed. Results: Accurate life-sized 3D cardiac prototypes were successfully created for all patients. The models enabled radically improved 3D understanding of anatomy, identification of specific technical challenges, and precise surgical planning. Augmentation of existing clinical and imaging data by 3D prototypes allowed successful execution of complex surgeries for all five patients, in accordance with the preoperative planning. Conclusions: 3D-printed cardiac prototypes can radically assist decision-making, planning, and safe execution of complex congenital heart surgery by improving understanding of 3D anatomy and allowing anticipation of technical challenges.

Diffusion-weighted magnetic resonance imaging in acute reversible toxic leukoencephalopathy: A report of two cases

Acute toxic leukoencephalopathy may be caused by endogenous or exogenous toxins. It may reverse clinically if the offending agent is withdrawn or the underlying condition is treated. However, demonstration of reversibility on imaging, especially with diffusion-weighted MRI, has been reported only very recently. We report two such cases.

Utility of C-arm CT in overcoming challenges in patients undergoing Transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the well-known treatment for hepatocellular carcinoma. Multiple digital subtraction angiography (DSA) acquisitions in different projections are required to identify difficult arterial feeders. Moreover, the tell-tale tumor blush can be obscured by proximity to lung base, small size of lesion, and breathing artifacts. C-arm CT is a revolutionary advancement in the intervention radiology suite that allows acquisition of data which can be reformatted in multiple planes and volume rendered incorporating both soft tissue and vascular information like multidetector computed tomography (MDCT). These images acquired during the TACE procedure can provide critical inputs for achieving a safe and effective therapy. This case series aims to illustrate the utility of C-arm CT in solving specific problems encountered while performing TACE.

Understanding the physiology of complex congenital heart disease using cardiac magnetic resonance imaging.

Complex congenital heart diseases are often associated with complex alterations in hemodynamics. Understanding these key hemodynamic changes is critical to making management decisions including surgery and postoperative management. Existing tools for imaging and hemodynamic assessment like echocardiography, computed tomography and cardiac catheterization have inherent limitations. Cardiac magnetic resonance imaging (MRI) is emerging as a powerful bouquet of tools that allow not only excellent imaging, but also a unique insight into hemodynamics. This article introduces the reader to cardiac MRI and its utility through the clinical example of a child with a complex congenital cyanotic heart disease.

Imaging in diabetic ischemic foot

Diabetic microangiopathy largely affects the infrapopliteal vessels. Extensive infrapopliteal calcification and occlusions, without the presence of collaterals, are common in diabetic patients. When the diabetic patient presents with a nonhealing ulcer, the investigation of first choice should be duplex ultrasound. Ultrasound is not only safe and noninvasive, it also serves to guide further patient management. In a subset of patient in whom intervention is planned, catheter angiogram is the best choice; if the patient has diabetic nephropathy, MR angiogram is an alternative. Multidetector computed tomography angiogram is not a preferred modality in the diabetic patient because there is likely to be extensive calcification in infrapopliteal vessels.

From establishing a CHD-CMR unit to 3D printing in a developing country pediatric cardiac unit

Background Units providing specialised, advanced care for children and adults with CHD are few and far-in-betwen in developing nations, despite having the greater proportion of the world’s burden of CHD. CHD scores low among the health care priorities of the State in most low-medium income countries (LMIC).However, centers of excellence in CHD care have emerged even in these environments with results matching those in developed nations. Among the last and least to develop in such limited resource environments are the modalities for advanced imaging. Cardiac MRI, in particular, has been late to emerge, and is yet to gain adequate foothold. Reasons : high infrastructural cost, highly expertise intensive, effor and time intensive. There are no dedicated CMR training programs in most developing countries including India. We attempt to trace the birth and steady growth of a dedicated CHD-CMR unit in a developing nation.

Percutaneous transluminal angioplasty and stenting in the management of chronic mesenteric angina: A single center experience

Introduction: The objective of our study was to review the results of percutaneous angioplasty (PTA)/stenting in the treatment of patients who presented with symptoms and angiographic findings of chronic mesenteric ischemia (CMI). Materials and Methods: We performed a retrospective analysis of 13 consecutive patients from a single institution who underwent PTA/stenting for the treatment of symptoms suggestive of CMI. Results: All 13 patients in our study were men, and most common presenting symptoms were weight loss and postprandial pain. Atherosclerosis was the most common cause. PTA and stenting was performed in 9 patients and PTA alone was done in 4 patients. Primary technical success rate was 92% with complete resolution of symptoms within 2 weeks in all patients. No statistical difference was noted in primary clinical success rate based on the number of vessels treated or the method of treatment. However, in patients whom SMA was treated had longer duration of symptom-free survival as compared to other vessels. Conclusion: PTA and stenting are very effective therapeutic options for patients presenting with CMI symptoms. It should be considered as the first-line of management in such patients.