Simian crease (SC), a single transverse crease that extends from across the palm of the hand. The presence of a single transverse palmar crease or the SC can be, but not always, a symptom associated with abnormal medical conditions. In dysmorphology, the clinical significance of variability of palmar creases especially SC are widely recognized and have occurred more frequently in patients with various congenital anomalies that are caused by genetic as well as environmental insults in the first half of pregnancy. SC has been studied extensively in children especially with Down’s syndrome (DS) where the incidence of SC is more than 63%. In this case report, two families are discussed with relevance to the presence of SC. The first family with two children with DS have no SC in any of them, whereas the second healthy family only the father who is a doctor by profession having an SC.