Al-Arrayed (personal communication, 20.1.2007) reported a 6-year-old Bahraini boy born to non-consanguineous family with Holt-Oram syndrome.  The boy exhibited a right radial club hand with absent right thumb grade 1V.  He also had calcanovalgus in both ankles; however, in the right elbow movement was but stiff.  The boy also had features of congenital cyanotic heart disease, tetralogy of Fallot, and an inactive gastro-esophageal reflux.  In addition, he presented with right orbicularis oris hypoplasia (partial nerve palsy) and a vertebral anomaly (bifid T-3).  The boy was developmentally normal and ultrasound revealed normal renal profile.

Boehme and Shotar (1989) described a Jordanian family of normal intelligence in which members of three generations had complex malformations of the arms combined with variably expressed congenital heart disease. Because of the pedigree pattern, which included one instance of male-to-male transmission, they suggested autosomal dominant inheritance, but concluded that the disorder was distinct from Holt-Oram syndrome.

Al Madani (2008) reported a rare case of a patient with sporadic Holt-Oram syndrome, accompanied with double outlet right ventricle, valvular and sub-valvular pulmonary stenosis, persistent left superior vena cava draining to the left atrium, and an ectopic right kidney.

[Al Madani A. The Holt-Oram syndrome with double outlet right ventricle with valvular and subvalvular pulmonary stenosis. Kuwait Med J. 2008; 40(4):315-7.]

Elias and Karouny (1991) reported two subjects of the same family (a father and his daughter) with Holt-Oram syndrome. The two years' old child presented bilateral upper limb abnormalities with a large patent ductus arteriosus, rarely associated with this syndrome. She was operated for a ligation and resection of the patent ductus arteriosus. The girl had two (twin) brothers, 6-months-old, who were completely normal. The father presented bilateral upper limb abnormalities without congenital heart disease.

[Elias G, Karouny E. Holt-Oram syndrome: report of two cases. Rev Med Libanaise. 1991; 3:106-8.]

Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in an Omani hospital in Nizwa. Of the 21,988 total births in the hospital, one child was born with Holt-Oram Syndrome. Sawardekar (2005) hinted for a possible genetic contribution in this child.

Najjar et al. (1988) studied three families in which patients with the Holt-Oram syndrome had various skeletal abnormalities and congenital heart defects. Patient 1 was a 1-month-old Saudi boy born to first cousin parents and admitted for cyanosis, congenital absence of both thumbs, and congestive heart failure. Examination showed absence of the thumbs and of the first metacarpals, and hypoplastic radii. Patient 2 was a 9-year-old Saudi girl born to first cousin parents and referred for evaluation of heart murmur and easy fatigability. Patient 2 had pulmonary stenosis, an atrial septal defect, and triphalangeal thumbs. A sister had atrial septal defect and abnormalities of the thumbs; two brothers had abnormalities of the thumbs. The mother had unilateral defect of the thumb with a normal heart. Patient 3 was an 18-year-old Saudi girl with deformed left arm, tetralogy of Fallot, and hypoplastic pulmonary artery. In two families the Holt-Oram syndrome appeared to be the result of new mutations; in one it was transmitted as an autosomal dominant trait.

Megahed (1988) described a small-for-date female neonate of Emirati nationality with Holt-Oram syndrome showing complete phocomelia of the left upper limb with absent thumb and index finger. Right thumb was also absent. Examination of the heart revealed normal heart sounds and the presents of a soft pansystolic murmur of fourth degree. The femoral pulses were adequately palpated. X-ray showed absence of the left humerus, radius and ulna, left first and second metacarpals and phalangeal bones and right first metacarpals and phalangeal bones. Echocardiography showed ventricular septal defect. Family history revealed consanguinity of third degree. The father was normal but the mother had a fingerized left thumb and an atrial septal defect. Four of their children were normal, and two abnormal - a girl with absent left thumb and a boy with bilateral long thumbs. In addition one boy died on day 7 of birth from undiagnosed congenital heart disease. He also showed complete bilateral phocomelia.

[Megahed MAE-S. Holt Oram syndrome. Emirates Med J 1988; 6:94-6.]