36 https://www.id-press.eu/mjms/index Scientifc Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 May 10; 8(C):36-40. https://doi.org/10.3889/oamjms.2020.4287 eISSN: 1857-9655 Category: C - Case Reports Section: Case Report in Pediatrics Holt–Oram Syndrome Associated with Complex Congenital Heart Disease: A Rare Case Presentation and Literature Review Bejiqi Ramush 1,2,3 , Retkoceri Ragip 3 , Maloku Arlinda 3 , Mustafa Aferdita 3 , Bejiqi R. Rinor 4 * 1 Texas Health Science Center, University of Texas, San Antonio, Texas, USA; 2 University of Gjakova “Fehmi Agani,” Medical School, Gjakova, Kosovo; 3 Department of Cardiology, Pediatric Clinic, University Clinical Center of Kosovo, Prishtina, Kosovo; 4 Polyclinic “Echoscan”, Prishtina, 10000 Kosovo Abstract BACKGROUND: First described by Holt and Oram in 1960 in a four-generation family with atrial septal defects and thumb abnormalities, is an inherited disorder characterized by abnormalities of the upper limbs and heart. This syndrome is characterized by upper extremity malformations involving radial, thenar, or carpal bones. An abnormal carpal bone is present in all affected individuals and may be the only evidence of disease. About 75% of individuals with Holt–Oram syndrome (HOS) have a congenital heart malformation which may include an atrial or ventricular septal defect or heart block. In rare cases, the syndrome can affect other organs and systems which can be life threatening. CASE REPORT: Here, we present a newborn with clinical and radiologic features of HOS consisting of bilateral asymmetric hypoplastic thumbs, generalized brachydactyly, limited bilateral supination due to radioulnar synostosis, and associated with complex heart disease and hypoplastic tricuspid valve. CONCLUSION: In our case HOS is associated with complex congenital heart defects including atrial septal defect, ventricular septal defect with hypoplastic tricuspid valve. Based on the listed literature we didn’t fnd any other case where tricuspid valve was affected. Edited by: Igor Spiroski Citation: Ramush B, Ragip R, Arlinda M, Aferdita M, Rinor BR. Holt–Oram Syndrome Associated with Complex Congenital Heart Disease: A Rare Case Presentation and Literature Review. Open Access Maced J Med Sci. 2020 May 10; 8(C):36-40. https://doi.org/10.3889/oamjms.2020.4287 Keywords: Atriodigital syndrome; TBX5 gene; Congenital heart disease; Hypoplastic tricuspid valve *Correspondence: Bejiqi R. Rinor, Polyclinic “Echoscan”, Prishtina, 10000 Kosovo. Phone: +383 49 585564. E-mail: rinorbejiqi25@gmail.com Received: 09-Jan-2020 Revised: 14-Mar-2020 Accepted: 21-Apr-2020 Copyright: © 2020 Bejiqi Ramush, Retkoceri Ragip, Maloku Arlinda, Mustafa Aferdita, Bejiqi R. Rinor Funding: This research did not receive any fnancial support. Competing Interests: The authors have declared that no competing interest exists. Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC 4.0) Introduction Holt–Oram syndrome (HOS) (also called an atriodigital syndrome, atriodigital dysplasia, cardiac- limb syndrome, heart-hand syndrome type 1, HOS, and ventriculo-radial syndrome) is an autosomal dominant very rare disorder that affects bones in the arms and hands (the upper limbs) and often causes heart problems [1]. HOS is the most common of the heart- hand syndromes with the estimated prevalence between 0.7 and 1/100,000 births. HOS has been reported from a number of countries worldwide and in individuals of different racial and ethnic backgrounds [2]. Bone abnormalities may affect only one side of the body or both sides; if both sides are affected differently, the left side is usually affected more severely. About 75% of individuals with HOS also have congenital heart problems, with the most common being defects – atrial or ventricular septal defect (VSD) [3]. The most common problem is ostium secundum atrial septal defect (ASD) and VSD, especially those occurring in the muscular trabeculated septum and cardiac conduction disease. So far, no signs of heart valve disease have been reported. Case Report A mail newborn weighing 3200 g from the normal pregnancy and normal delivery at 39 weeks of gestation was done. At the delivery, the baby was normal with an Apgar score of 8 and 9 at 1 and 5 min, respectively, and a SaO 2 level of 92%. The previous family medical history was unremarkable, and there was no family history of congenital malformation. During pregnancy by the obstetrician, some routine echosonographic examinations have been made, and no any morphological or heart disease has been referred. During the frst postnatal routine clinical examination, complex morphological deformities of upper extremities have been registered. Both auricles of the ear were deformed with the normal external canal (Figures 1 and 2). Furthermore, hypospadia Grade I and right reponible inguinal hernia were noted (Figure 3). The chest X-ray was normal (Figure 4). The electrocardiogram presented normal sinus rhythm, right axis deviation, and incomplete block of the right bundle branch. Routine X-ray of upper extremities showed bilateral and symmetric upper limb malformations which include unequal