Variability of cardiac and limb involvement in the Holt-Oram syndrome

ABSTRACT

Holt-Oram Syndrome [HOS] is a rare genetic disorder characterized by variable degrees of malformations of the upper limbs and/or congenital heart disease. We present here nine affected cases, eight in three families and one sporadic case who exhibited variable features of the syndrome and showed a wide spectrum of abnormalities involving the skeletal system, specially the upper limbs, and cardiovascular system. This is probably the second report of Holt-Oram syndrome in Egyptians. The first report was in 1970 by Temtamy and El-Mazny[1]. The etiology of HOS is autosomal dominant disorder mostly due to mutation in TBX5, a box containing transcription factor. It has been suggested that SALL4 mutations might cause HOS. It is important to study the occurrence and spectrum of severity of HOS particularly in relation to the types of mutations affecting TBX5 and SALL4