CHRISMED Journal of Health and Research

: 2019  |  Volume : 6  |  Issue : 2  |  Page : 119--122

Holt–Oram syndrome – Case series of two reports

Mohd Ilyas, Arif Ahmad Wani, Zubair Ahmad, Mir Junaid Ahmad Kazimi, Naseer A Choh 
 Department of Radiodiagnosis, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Correspondence Address:
Mohd Ilyas
Department of Radiodiagnosis, Sher-I-Kashmir Institute of Medical Sciences, Srinagar - 190 011, Jammu and Kashmir


Holt–Oram syndrome is a rare genetic autosomal dominant disorder which affects the upper limbs and heart. It is also known as “heart–hand” syndrome or “atriodigital dysplasia.” The present article describes the clinical and radiological images of the features of Holt–Oram syndrome in two patients.

How to cite this article:
Ilyas M, Wani AA, Ahmad Z, Ahmad Kazimi MJ, Choh NA. Holt–Oram syndrome – Case series of two reports.CHRISMED J Health Res 2019;6:119-122

How to cite this URL:
Ilyas M, Wani AA, Ahmad Z, Ahmad Kazimi MJ, Choh NA. Holt–Oram syndrome – Case series of two reports. CHRISMED J Health Res [serial online] 2019 [cited 2021 Apr 17 ];6:119-122
Available from:

Full Text


Holt–Oram syndrome is a rare disorder with an incidence of approximately 1 in 1,00,000 live births. It is a hereditary disorder with autosomal dominant nature and has complete penetrance. The major features of this entity include congenital-limb deformities, congenital heart abnormalities, and/or cardiac conduction defects. The limb abnormalities common to this syndrome are preaxial radial ray abnormalities such as radial agenesis and radial aplasia while the most common cardiac defects include atrial septal defect and ventricular septal defect.[1] It is linked to a single-gene TBX5 “protein-producing” mutation with gene map locus 12q24 and is the most commonly occurring heart–hand syndrome.[2],[3]

 Case Reports

Case 1

A 9-year-old female child was referred to the Department of Radiology for the evaluation of upper-limb deformities. The deformities were evident from birth but were neglected due to some financial constraints of the parents. She had all behavioral milestones appropriate for age. She gave a history of breathlessness on exertion. There was no history of any fever or palpitations. The family history was positive for upper-limb deformity in grandfather, but no exact record was available.

Clinically, the stature was appropriate for age. There were obvious bilateral forearm and hand deformities wherein the left forearm appeared shorter than the right with absent thumb on both sides [Figure 1]. The anteroposterior radiographs of both the forearms and hands were obtained. The radiographs revealed absent thumb bones on both sides, absent first metacarpal bone on both sides, and only two carpal bones (hamate and capitate) on both sides with absent radius on the left side [Figure 2]. The posteroanterior chest radiograph did not reveal any obvious abnormality [Figure 3].{Figure 1}{Figure 2}{Figure 3}

Cardiac magnetic resonance imaging was performed to assess for the cardiac abnormalities. The study was positive for 20 mm × 15 mm ostium secundum atrial septal defect (OS-ASD) [Figure 4]. The myocardial and valvular functions were normal.{Figure 4}

The diagnosis of Holt–Oram syndrome was formulated based on the clinical and radiologic evidence. The cardiothoracic surgery department performed the device closure of the OS-ASD, and the patient was referred to physical medicine and rehabilitation for physiotherapy regarding the skeletal deformities.

Case 2

An 11-year-old male child presented to the emergency medicine with the complaints of chest pain and breathlessness. There was no history of fever. The family history was inconclusive and no significant history. The emergency resident noticed the deformed bilateral upper limbs with flexion and internal rotation deformity at the wrist. The forearms were short with absent bilateral thumbs [Figure 5]. Skeletal radiographs of both the upper limbs were obtained. The radiographs revealed absent bilateral first metacarpal bone, absent bilateral thumb bones, absent second metacarpal and phalanges of the index finger on the left side, absent carpal bones on the left side, and presence of only five carpal bones on the right side. The radius was absent on the left side and hypoplastic on the right side [Figure 6]. The chest radiograph did not reveal any abnormality.{Figure 5}{Figure 6}

Cardiac evaluation by magnetic resonance imaging revealed about 2 cm membranous ventricular septal defect [Figure 7]. Sonographic evaluation of the abdomen revealed absent left kidney in this child [Figure 8].{Figure 7}{Figure 8}

The clinical and radiological evidence led to the diagnosis of Holt–Oram syndrome, and the patient was referred to physical medicine and rehabilitation and cardiovascular surgery for further management.


Holt–Oram syndrome refers to the congenital abnormalities involving the upper limbs and heart. It is caused due to single-gene TBX5 “protein-producing” mutation with gene map locus 12q24. It has autosomal dominant mode of inheritance. It was first described in 1960 by Holt and Oram.[4] It can be detected intrauterine during the anomaly scan presenting as abnormal upper-limb development. It is usually detected after birth.[5]

The cardinal manifestations of this syndrome include predominantly upper-limb deformities such as hypoplasia of thumb, clinodactyly, brachydactyly, triphalangeal thumbs, carpal bone dysmorphism, shortness of ulna, shortness of humerus, and aplasia of radius to phocomelia. The second major component of this syndrome includes cardiac abnormalities which may present as OS-ASD, ostium primum ASD, or ventricular septal defects.[6]

A number of other disorders may present as having cardiac defects and skeletal deformities similar to Holt–Oram syndrome such as thrombocytopenia-absent radius syndrome, Roberts syndrome, thalidomide embryopathy, and fanconi anemia. In Holt–Oram syndrome, the radial aplasia is associated with thumb aplasia or hypoplasia without any hematological disturbance and with a positive family history of limb deformities.[7]

It does not affect lower limbs because of the fact that mutant gene affects the embryogenesis during the 4th and 5th week of intrauterine life when the lower limbs are not differentiated.

The morbidity and mortality in these patients depend on the severity of cardiac defects and the stage of their diagnosis. Besides the simple defects, sometimes, rare complex cardiac defects may also been seen in Holt–Oram syndrome such as pulmonary stenosis, mitral valve prolapse, and arrhythmias in the form of atrioventricular blocks. More complex cardiac lesions such as tetralogy of Fallot, endocardial cushion defects, and total anomalous pulmonary venous return.

The main aim of management includes the physical therapy to at least provide some function to the deformed upper limbs and primarily the detection of the cardiac abnormalities so that they can be corrected at an early stage to prolong the longevity of patients.[8]


The Holt–Oram syndrome is a rare disorder with a constellation of upper-limb deformities and cardiac defects. The aim of this article was to present the classic findings in two cases of Holt–Oram syndrome in which cardiac defects were detected early and repaired. All the patients with upper-limb deformities should be evaluated for cardiac defects so that early management is planned.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Basson CT, Bachinsky DR, Lin RC, Levi T, Elkins JA, Soults J, et al. Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet 1997;15:30-5.
2Basson CT, Cowley GS, Solomon SD, Weissman B, Poznanski AK, Traill TA, et al. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) N Engl J Med 1994;330:885-91.
3Rodagi SB, Surana SS, Potdar VR, Kirdi SS. Holt-Oram syndrome associated with aortic atresia: A rare association. Heart Views 2016;17:27-9.
4Holt M, Oram S. Familial heart disease with skeletal malformations. Br Heart J 1960;22:236-42.
5Sletten LJ, Pierpont ME. Variation in severity of cardiac disease in Holt-Oram syndrome. Am J Med Genet 1996;65:128-32.
6Shankar B, Bhutia E, Kumar D, Kishore S, Das SP. Holt-Oram syndrome: A rare variant. Iran J Med Sci 2017;42:416-9.
7Tidake A, Gangurde P, Shaikh Z, Mahajan A. Tetralogy of Fallot with Holt-Oram syndrome: Case report and review. Clin Res Cardiol 2015;104:790-3.
8Wall LB, Piper SL, Habenicht R, Oishi SN, Ezaki M, Goldfarb CA. Defining features of the upper extremity in Holt-Oram syndrome. J Hand Surg Am 2015;40:1764-8.