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Heterotaxy Syndrome and Primary Ciliary Dyskinesia Clinical Presentation

  • Author: Alvin J Chin, MD; Chief Editor: Stuart Berger, MD  more...
 
Updated: May 09, 2014
 

History

Patients with heart malformations most frequently present with cyanosis in the first few days of life due to subpulmonary stenosis or atresia. Some individuals with subaortic stenosis and aortic arch obstruction present with poor perfusion. Severe common atrioventricular valve regurgitation, contributing to low output syndrome, is another possible presentation. A small percentage of patients with heterotaxy are first identified because of abdominal pain and vomiting related to malrotation-caused intestinal obstruction.

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Physical

Cyanosis (if subpulmonary stenosis or atresia is present) or poor peripheral perfusion (if severe aortic arch obstruction or common atrioventricular valve regurgitation is present) are the most common findings. The liver may be on the left, rather than the right, and it may span the abdomen. Dextrocardia may be identifiable. Patients who present because of malrotation-caused obstruction may have abdominal distension, bilious vomiting, and rarely melena.

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Causes

More than 60 genes have been identified as required for normal left-right axis specification, left-right patterning, or respiratory ciliary function.[17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41]

See the image below.

Genes required for proper left-right asymmetry areGenes required for proper left-right asymmetry are shown. Genes are presented in 5 columns, according to the developmental phase in which they are currently thought to function. The leftmost column has the earliest functioning genes. The second column has genes required for the development of the node (or its equivalent). The third and fourth column have genes that are required for normal node cilia function. Genes in white, green, or blue denote those in which the proof came from studies of fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), or frog (Xenopus laevis), respectively. Genes in brown are those studied in mouse (Mus musculus), whereas those discovered in human (Homo sapiens) are shown in red.
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Contributor Information and Disclosures
Author

Alvin J Chin, MD Emeritus Professor of Pediatrics, University of Pennsylvania School of Medicine

Alvin J Chin, MD is a member of the following medical societies: American Association for the Advancement of Science, Society for Developmental Biology, American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Julian M Stewart, MD, PhD Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College

Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Autonomic Society, American Physiological Society

Disclosure: Received grant/research funds from Lundbeck Pharmaceuticals for none.

Chief Editor

Stuart Berger, MD Medical Director of The Heart Center, Children's Hospital of Wisconsin; Associate Professor, Department of Pediatrics, Section of Pediatric Cardiology, Medical College of Wisconsin

Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Additional Contributors

Charles I Berul, MD Professor of Pediatrics and Integrative Systems Biology, George Washington University School of Medicine; Chief, Division of Cardiology, Children's National Medical Center

Charles I Berul, MD is a member of the following medical societies: American Academy of Pediatrics, Heart Rhythm Society, Cardiac Electrophysiology Society, Pediatric and Congenital Electrophysiology Society, American College of Cardiology, American Heart Association, Society for Pediatric Research

Disclosure: Received grant/research funds from Medtronic for consulting.

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The structure and function of cilia is shown here. (A) Most motile cilia are organized with 9 microtubule doublets surrounding a core pair of doublets (9+2 configuration). Outer dynein arms (green) and inner dynein arms (blue) are shown. Cilia on the cells of the ventral node in the normal mouse embryo have no core doublet (a 9+0 configuration) and were initially thought to be nonmotile; however, upon closer scrutiny, node cilia were seen to have a rotatory motion (600 rpm). [Figure A is from Hirokawa N, Tanaka Y, Okada Y. Left-right determination: involvement of molecular motor KIF3, cilia, and nodal flow. Cold Spring Harb Perspect Biol. Jul 2009;1(1):a000802 and is reprinted with permission of Cold Spring Harbor Press](B) lrd (left-right dynein), the protein (green) mutated by the iv mutation, is also known as DNAH11, DNAHC11, and DLP11. [Figure B is from the United States Department of Energy Genomes to Life Program](C) The rotatory cone of each cilium is tilted posteriorly. Hence, the cilia make a leftward swing at the fluid surface and a rightward swing at the cellular surface. Because more viscous drag is present at the cellular surface, the rightward sweep is less effective at generating fluid movement than is the leftward sweep.[Figure C is from Hirokawa N, Tanaka Y, Okada Y, Takeda S. Nodal flow and the generation of left-right asymmetry. Cell 2006; 125:33-45 and is reproduced with permission from Cell Press]A = Anterior; L = Left; P = Posterior; R = Right.
Three phases of elaboration of LR asymmetry are shown. The first step consists of differentiating the left and right sides on the cellular level. This probably takes place by means of a chiral molecule. (A) A subset of the cells (yellow) of the fairly early embryo undergo this process.(B) Localized cellular asymmetry is propagated between cells to cause LR determinants to accumulate on one side of the embryonic midline, possibly by a process involving transport through gap junctions. These determinants would then induce cascades of factors in multicellular fields of the embryo. (C) Finally, the asymmetric presence of these factors induces or suppresses asymmetrically located organs such as the spleen and regulates asymmetric morphogenesis of other organs such as the heart tube.Courtesy of Levin M, Mercola M. The compulsion of chirality: toward an understanding of left-right asymmetry. Genes Dev. Mar 15 1998;12(6):763-9.
Genes required for proper left-right asymmetry are shown. Genes are presented in 5 columns, according to the developmental phase in which they are currently thought to function. The leftmost column has the earliest functioning genes. The second column has genes required for the development of the node (or its equivalent). The third and fourth column have genes that are required for normal node cilia function. Genes in white, green, or blue denote those in which the proof came from studies of fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), or frog (Xenopus laevis), respectively. Genes in brown are those studied in mouse (Mus musculus), whereas those discovered in human (Homo sapiens) are shown in red.
Axial MRI of a case of heterotaxy with polysplenia. (A) The abdominal aorta (abd ao) is on the left side of the spine (S), as is the left-sided azygos (L Azy). Two right-sided spleens (spl) are visible. LHV = Left hepatic vein; RHV = Right hepatic vein.(B) A common atrioventricular valve (black unlabelled arrows) is markedly malaligned to the right ventricle (RV). A diminutive left atrium (LA) is represented by only an appendage. The patient had an extracardiac conduit (EC) type of Fontan operation. No fenestration is noted between the EC and the neo-left atrium (neoLA). (C) Because this patient had subaortic stenosis, a proximal pulmonary artery-to-ascending aortic anastomosis was performed early in life, along with augmentation of the aortic arch. The L Azy connects to the left superior vena cava (LSVC). LU DAo = Left upper descending aorta; Prox = Proximal. (D) The LSVC connected originally to the coronary sinus (CS) and then to the right atrium. Despite the fact that the LSVC has been disconnected from the heart and anastomosed end-to-side to the left pulmonary artery, the CS remains large. The narrowed left ventricular outflow tract (LVOT) is seen. Ao = Aorta; PA = Pulmonary root; RLL PV = Right lower lobe pulmonary vein. (E) Because this patient had absence of the hepatic segment of the inferior vena cava, the left-sided SVC-to-left pulmonary artery (LPA) anastomosis is referred to a left-sided Kawashima (LK). The anastomosis of the right superior vena cava to the right pulmonary artery is a right-sided bidirectional Glenn (R BDG) shunt. (F) The left lower lobe pulmonary vein (LLL PV), as part of this patient's totally anomalous pulmonary venous connection, connects to the original right atrium, which is now the neoLA.
Coronal MRI of the patient shown in media file 4. (A) Both superior vena cava (SVC)–to–pulmonary artery (PA) anastomoses can be seen. LCCA = Left common carotid artery. (B) Three dimensional surface rendering. RIA = Right innominate artery. (C) Three-dimensional reconstruction of only the systemic venous pathway.
Malrotation of the gut. This upper GI barium study of the heterotaxy patient shown in media files 4 and 5 shows a right-sided stomach (St), opposite of normal. The duodenum heads to the left, the duodenal-jejunal junction is to the left of the spine (opposite to what would be expected for situs inversus totalis), and the jejunum (J) stays left-sided.
 
 
 
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