holt - oram syndrome ( hos ) is an autosomal dominant condition with complete penetrance . manifested in 1:1 , 00 , 000 live births and characterized by forelimb deformities , congenital heart disease and/or cardiac conduction abnormalities .
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 .
congenital cardiac and upper limb malformations frequently occur together and are classified as heart hand syndromes .
the most common among the heart hand disorders is hos , which is characterized by cardiac septation defects and preaxial radial ray abnormalities .
this condition with a high rate ( 3085% ) of new non - familial cases was first described by holt and oram in 1960 in a 4-generation family with atrial septal defects ( asd ) and thumb abnormalities .
the most common cardiac disorder is an ostium secundum asd , followed by ventricular septal defect ( vsd ) and ostium primum asd .
electrocardiogram ( ecg ) abnormalities such as various degrees of atrioventricular ( av ) block have also been reported .
a full term female neonate born out of a nonconsanguineous marriage by cesarean section ( indication - previous cesarean section with polyhydramnios ) to a 25-year - old ( weight  58 kg , height  155 cm ) booked g3p1l1a1 with unremarkable antenatal history .
family history revealed that the father has radial ray deformity of left upper limb without any cardiac anomaly .
physical examination revealed an active baby weighing 2790 g and length of 49 cm , heart rate of 146/min , blood pressure of 70/30 mm of hg , respiratory rate of 40/min , and systemic oxygen saturation of right upper limb being 83% in room air and that of right lower limb being 74% in room air [ figure 1 ] . on musculoskeletal examination , left upper limb shortening was noticed with absent radius bone , radial flexion deformity of the wrist and also absent thumb [ figure 2 ] .
no obvious deformities were noticed elsewhere . on cardio - vascular system examination , the pansystolic murmur of grade iii at the mitral and left parasternal area was heard
picture showing the baby of holt - oram syndrome left upper limb showing radial ray deformity with absent thumb right hand showing triphalangeal thumb on further investigation , chest x - ray showed normal thoracic situs with cardiomegaly , plain radiograph of both upper limbs revealed absent radius on left side with absent carpal bones and absent first metacarpal bone and phalanges ( thumb ) , right side showing absent carpal bones and triphalangeal thumb [ figure 4 ] .
plain radiograph showing the bony deformities of the upper limb with cardiomegaly the baby developed cyanosis couple of hours after delivery , following which an ecg was done which was normal and a 2d echocardiography was done which revealed severe aortic atresia with hypoplastic arch , large perimembranous vsd and asd as well [ figure 5 ] .
the neonate was referred to a cardiac center for further management , however due to lack of resources the baby died on day 4 of life .
holt - oram syndrome is an autosomal dominant disorder characterized by distinctive malformation of bones of the upper limbs and abnormalities of the heart .
cardinal manifestations of hos are dysplasia of upper limb that ranges from minor findings including hypoplasia of thumb , clinodactyly , brachydactyly , triphalangeal thumbs , carpal bone dysmorphism , shortness of ulna , shortness of humerus , aplasia of radius to phocomelia and cardiac abnormalities .
although bilateral , left side is often affected more significantly . in a study of 98 subjects with hypoplastic thumbs , 16% proved to be the cases of hos .
there are many well described heart - hand syndromes characterized by deformities of the radial ray and congenital heart defects such as thrombocytopenia absent radius syndrome , roberts syndrome , thalidomide embryopathy , and fanconi anemia .
the unique feature that helps to differentiate these from hos is that the radial aplasia is associated with hypoplasia / absence of the thumb without any hematological abnormalities and there is often a family history of heart and limb defects .
the associated congenital heart defects are the most important determining factors in morbidity and mortality in these patients .
other cardiac associations include 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 are observed in 18% of subjects with hos .
the association with aortic atresia is extremely rare . as per best of our knowledge ,
till date there were no cases reported in the literature having a description of hos with aortic atresia .
the electrocardiographic abnormalities such as variable degree of av blocks have also been reported , but in our case no conduction defects were noted .
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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 can not be guaranteed .
 holt - oram syndrome ( hos ) is a rare autosomal dominant disorder that causes abnormalities of the upper limbs and heart . 
 it is seen in 1:1 , 00 , 000 live births . 
 it is linked to a single - gene tbx5  protein - producing  mutation with gene map locus 12q24 . 
 most commonly it is characterized by the cardiac septation defects and pre - axial radial ray abnormalities . 
 we are reporting a case of hos with aortic atresia which is a rare association . 